Licochalcone A induces cell cycle arrest in human lung squamous carcinoma cells via the PI3K/Akt signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of licochalcone A (LCA) on the proliferation and cell cycle of human lung squamous carcinoma cells and explore its possible molecular mechanism.@*METHODS@#MTT assay was used to detect the changes in proliferation of H226 cells after treatment with different concentrations of LCA for 48 h, and the IC50 of LCA was calculated. Flow cytometry was used to analyze cell cycle changes in H226 cells treated with 10, 20, and 40 μmol/L LCA, and the expressions of cyclin D1, cyclin-dependent kinase CDK2 and CDK4, and p-PI3K, PI3K, p-Akt, and Akt in the treated cells were detected using Western blotting. The effect of intraperitoneal injection of LCA for 24 days on tumor volume and weight was assessed in a BALB/c-nu mouse model bearing lung squamous carcinoma xenografts.@*RESULTS@#MTT assay showed that LCA significantly decreased the viability of H226 cells with an IC50 of 28.3 μmol/L at 48 h. Flow cytometry suggested that LCA treatment induced obvious cell cycle arrest at the G1 phase. LCA treatment also significantly decreased the expressions of cyclin D1, CDK2, and CDK4, and inhibited the phosphorylation of PI3K and Akt in H226 cells. In the tumor-bearing mice, LCA treatment for 24 days significantly reduced the tumor volume and weight.@*CONCLUSION@#LCA is capable of inhibiting the proliferation and inducing cell cycle arrest in lung squamous carcinoma cells possibility by regulating the PI3K/Akt singling pathway.

Construction of a prediction model for lung cancer combined with chronic obstructive pulmonary disease by combining CT imaging features with clinical features and evaluation of its efficacy / 中华放射学杂志

Objective:To assess the effectiveness of a model created using clinical features and preoperative chest CT imaging features in predicting the chronic obstructive pulmonary disease (COPD) among patients diagnosed with lung cancer.Methods:A retrospective analysis was conducted on clinical (age, gender, smoking history, smoking index, etc.) and imaging (lesion size, location, density, lobulation sign, etc.) data from 444 lung cancer patients confirmed by pathology at the Second Affiliated Hospital of Naval Medical University between June 2014 and March 2021. These patients were randomly divided into a training set (310 patients) and an internal test set (134 patients) using a 7∶3 ratio through the random function in Python. Based on the results of pulmonary function tests, the patients were further categorized into two groups: lung cancer combined with COPD and lung cancer non-COPD. Initially, univariate analysis was performed to identify statistically significant differences in clinical characteristics between the two groups. The variables showing significance were then included in the logistic regression analysis to determine the independent factors predicting lung cancer combined with COPD, thereby constructing the clinical model. The image features underwent a filtering process using the minimum absolute value convergence and selection operator. The reliability of these features was assessed through leave-P groups-out cross-validation repeated five times. Subsequently, a radiological model was developed. Finally, a combined model was established by combining the radiological signature with the clinical features. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were plotted to evaluate the predictive capability and clinical applicability of the model. The area under the curve (AUC) for each model in predicting lung cancer combined with COPD was compared using the DeLong test.Results:In the training set, there were 182 cases in the lung cancer combined with COPD group and 128 cases in the lung cancer non-COPD group. The combined model demonstrated an AUC of 0.89 for predicting lung cancer combined with COPD, while the clinical model achieved an AUC of 0.82 and the radiological model had an AUC of 0.85. In the test set, there were 78 cases in the lung cancer combined with COPD group and 56 cases in the lung cancer non-COPD group. The combined model yielded an AUC of 0.85 for predicting lung cancer combined with COPD, compared to 0.77 for the clinical model and 0.83 for the radiological model. The difference in AUC between the radiological model and the clinical model was not statistically significant ( Z=1.40, P=0.163). However, there were statistically significant differences in the AUC values between the combined model and the clinical model ( Z=-4.01, P=0.010), as well as between the combined model and the radiological model ( Z=-2.57, P<0.001). DCA showed the maximum net benifit of the combined model. Conclusion:The developed synthetic diagnostic combined model, incorporating both radiological signature and clinical features, demonstrates the ability to predict COPD in patients with lung cancer.

Value of CT pulmonary vascular quantitative parameters in diagnosis of chronic obstructive pulmonary disease patients and high-risk groups / 中华放射学杂志

Objective:To explore the diagnostic value of CT pulmonary vascular quantitative parameters in patients with chronic obstructive pulmonary disease (COPD) and high-risk groups.Methods:A retrospective study of 1 126 patients who underwent chest CT examination and pulmonary function test in Shanghai Tongji Hospital from January 2015 to August 2020. According to lung function, they were divided into COPD group (471 cases), high-risk group (454 cases), and normal control group (201 cases). Pulmonary vascular parameters on chest CT, including the total number of vessels (N total), the number cross-sectional area of vessels under 5 mm 2 (N CSA<5), lung surface area (LSA), number of pulmonary blood vessels per unit lung surface area (N total/LSA) and the total area of vessels (VA total) at a 9, 15, 21 mm depth from the pleural surface, and the total blood vessel volume (TBV), blood vessel volume under 5 mm 2 and 10 mm 2(BV5 and BV10) were measured quantitatively. Kruskal-Wallis H test was used to compare the differences of quantitative parameters of pulmonary vascular in the three groups; Spearman rank test was used to analyze the correlation between CT pulmonary vascular parameters and pulmonary function. Results:There were significant differences in N total/LSA at a 9, 15, 21 mm depth from the pleural surface among three groups ( P<0.05). There were significant differences in N CSA<5, N total at a 9 mm depth from the pleural surface among three groups ( P<0.05). There were significant differences in LSA at a 9 mm depth from the pleural surface, N CSA<5, N total, LSA, VA total at a 15, 21 mm depth from the pleural surface and TBV, BV5 and BV10 among three groups ( P<0.05). In high-risk group, there were positive correlation between N total/LSA, VA total at a 9 mm depth from the pleural surface and some pulmonary function parameters ( r=0.095-0.139, P<0.05). N CSA<5, N total, LSA, N total/LSA, TBV, BV5 and BV10 at different depth from pleural surface were negatively correlated with some pulmonary function parameters ( r=-0.110--0.215, P<0.05). In COPD group, number of vessels at a 9 mm depth from the pleural surface was positively correlated with the diffusion capacity for carbon monoxide of the lung single breath ( r=0.105, 0.103, P<0.05). In addition to N total/LSA were positively correlated with lung function parameters ( r=0.181-0.324, P<0.05), the remaining pulmonary vascular parameters were negatively correlated with some pulmonary function parameters ( r=-0.092--0.431, P<0.05). Conclusion:Quantitative chest CT imaging are able to effectively evaluate pulmonary vascular changes in COPD patients and high-risk groups, and the quantitative parameters of pulmonary vascular CT may distinguish COPD from high-risk groups, providing a novel means for early diagnosis of COPD and prediction of high-risk groups.

The impact of flash glucose monitoring on glycemic control, residual islet function, and patient-reported outcomes in children and adolescents with newly diagnosed type 1 diabetes / 中国医师杂志

Objective:To assess the effect of flash glucose monitoring (FGM) compared with self-monitoring of blood glucose (SMBG) on glycemic control, residual islet function, and patient-reported outcomes in children and adolescents with newly diagnosed type 1 diabetes within 1 year.Methods:133 children and adolescents with newly diagnosed T1DM in the T1D clinic of the Second Xiangya Hospital of Central South University from January 2016 to January 2020 were divided into two groups: FGM group ( n=82) and SMBG group ( n=51). The observation indexes included hemoglobin A1c (HbA 1c), fasting and postprandial blood glucose (FBG and 2 h BG), C-peptide (FCP and 2 h CP) during the one-year follow-up, Δ CP (2 h CP-FCP), patient-reported hypoglycemia and questionnaires regarding self-management of diabetes and quality of life. Results:At 6 months, HbA 1c in 2 groups was significantly decreased (all P<0.05); at 6 to 12 months, HbA 1c in FGM group tended to be stable ( P>0.05); at 12 months, HbA 1c in SMBG group was significantly increased compared with 6 months ( P=0.001). At 12 months, HbA 1c in SMBG group was higher than that in FGM group ( P=0.001). At 12 months, FBG in FGM group was equivalent to the baseline level ( P>0.05), while FBG in SMBG group was significantly higher than the baseline level ( P=0.006). 2 h BG only decreased at the 6th and 12th month in FGM group (all P<0.05). The FCP of SMBG group was significantly decreased at 12 months ( P<0.05), and the 2 h CP, Δ CP in the two groups decreased gradually (all P<0.05). FGM group had more hypoglycemic events at 6 and 12 months (all P<0.05). At 6 months, the score of Self-Management of T1D for Adolescents (SMOD-A) in FGM group was significantly improved ( P=0.001). During the follow-up period, the quality of life score of FGM group was stable ( P>0.05), while the quality of life score of SMBG group had a downward trend ( P=0.052). Conclusions:In newly diagnosed children and adolescents with T1DM, early application of FGM for blood glucose management will help to improve HbA 1c and reduce postprandial blood glucose. In addition, the self-management ability of children with FGM was improved after 6 months.

Synthesis and antibacterial activity of D-glucosamine-fluoroquinolone derivatives / 药学学报

Based on the idea of modification of sugar drugs, or transforming other active substances with sugar molecules, sixteen D-glucosamine-fluoroquinolone (FQ) derivatives were designed by combining D-glucosamine with FQs and synthesized by a multi-step reaction with shared intermediates. The assay results of anti-human pathogenic bacteria and anti-citrus canker showed that the inhibitory activities of two target molecules TM2b and TM2d against Staphylococcus aureus ATCC14125 were stronger than those of all tested positive control drugs, and the inhibitory rates of target molecules TM2m and TM2n against citrus canker were higher than that of the positive control streptomycin at the concentrations of 0.5 and 0.2 µg·mL-1, respectively, which all were worthy of further study. In this study, a series of novel molecules composed of D-glucosamine and FQs were synthesized for the first time, and super antibacterial molecules were found, which expanded the types and biological activities of D-glucosamine derivatives.

Frailty evaluation and risk factors for older patients with comorbidities: a cross-sectional study / 中华老年医学杂志

Objective:To investigate frailty in older patients with comorbidities and explore related risk factors.Methods:A cross-sectional study was conducted with an enrollment of 746 patients aged 65 years or older with comorbidities in the Wanshoulu Road area of Beijing from April 2019 to December 2020.A total of 617 patients with comorbidities were finally included, aged(85.6±4.8)years, including 358 women(58.0%); According to the FRAIL scale, 617 patients with comorbidities were divided into a frail group(156 cases, 25.3%)and a non-frail group(461 cases, 74.7%). Demographic data and information on comorbidities were collected.Univariate and multivariate Logistic regression analyses of risk factors were conducted.Results:Among 617 patients with comorbidities, the common chronic diseases in descending order were hypertension(497 cases, 80.6%), coronary heart disease(375 cases, 60.8%), osteoporosis(357 cases, 57.9%), osteoarthritis(281 cases, 45.5%), type 2 diabetes(211 cases, 34.2%), stroke and/or transient ischemic attack(193 cases, 31.3%), chronic lung disease(144 cases, 23.3%), tumor(133 cases, 21.6%), chronic kidney disease(92 cases, 14.9%), and heart failure(58 cases, 9.4%). Univariate logistic regression analysis showed that age, type 2 diabetes, coronary heart disease, heart failure, chronic lung disease, stroke/transient ischemic attack, cancer and osteoarthritis were influencing factors for frailty( P<0.05). Multivariate logistic regression analysis showed that age, type 2 diabetes, heart failure, chronic lung disease, cancer and osteoarthritis were risk factors for frailty( OR=1.076, 1.806, 3.275, 3.371, 1.640, 2.227, all P<0.05). Conclusions:Old age, type 2 diabetes, heart failure, chronic lung disease, tumor and osteoarthritis are closely related to frailty in elderly patients with comorbidities.Proactive and effective prevention and intervention should be instituted to target risk factors for frailty to reduce the occurrence of adverse outcomes.

Advances in medicinal research on tetrodotoxin / 药学实践杂志

Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine organisms. It has been used as an inhibitor of voltage-gated sodium channels (VGSCs), which could selectively bind to the α-subunit on the outer vestibule of VGSCs, preventing sodium ions from entering the channel, resulting in pharmacological activities. As a typical sodium channel blocker, TTX shows a significant analgesic effect. TTX could selectively block Na+ channels without affecting other ion channels, therefore it could reduce the probability of adverse reactions caused by commonly used antiarrhythmic drugs. In addition, TTX has a significant role in detoxification and prevention of renal failure, so TTX has great potential as a medicine. The structure and physicochemical properties, mechanism of action, pharmacological activities and preparations of tetrodotoxin have been reviewed in this paper, so as to provide a general support for the evaluation of its druggability and application in the field of pharmacy.

Retrospective Study of The Outcome of Primary Repair of Arteriovenous Fistula (AVF) Aneurysm and Pseudoaneurysm in Secondary Hospital Setting (Kajian Retrospektif Pembaikian Primer Ateriovenous Fistula (AVF) Aneurisma dan Pseudoaneurisma di Hospital Sekunder) / Jurnal Sains Kesihatan Malaysia

@#Aneurysms and pseudoaneurysm are commonly encountered with arteriovenous vascular access for haemodialysis. They are difficult complications to manage. Due to the limited number of vascular centers available, patients were unable to seek treatment until further complications arise. The technique of partial aneurysmectomy and primary repair was adopted as the method of repair in this study. A total of 20 cases underwent the surgery from 2019 to 2020. Among the 20 cases, one patient had two pseudoaneurysms at different location which requires her to undergo the procedure twice. The successful cannulation rate post repair was 70% whereas the overall complication rate was 35% which might be attributed to the small sample size. Overall, this study demonstrated that AVF aneurysm and pseudoaneurysm can be safely treated with this approach and can be done effectively in non-vascular centers by general surgeons.

Studies on orally disintegrating tablet of diphenhydramine hydrochloride and caffeine / 药学实践杂志

Objective To optimize the formulation and preparation of diphenhydramine hydrochloride and caffeine orally disintegrating tablet. Methods Melt granulation technology of steric acid and API was used to mask the unpleasant tasting of diphenhydramine hydrochloride. The tablets were prepared by direct pressing the dry powder with CCMC-Na as disintegrating agent. The formulation was optimized by orthogonal experiments to achieve the shortest disintegration time and the best taste correction. Results The optimized formula of orally disintegrating tablet was as follows： diphenhydramine hydrochloride 25 mg, caffeine 60 mg, stearic acid 25 mg, aspatan 40 mg, blueberry essence 7 mg, mannitol 45 mg, MCC 210 mg, CCMC-NA 25 mg, SDS 8 mg and magnesium stearate 5 mg. Conclusion This preparation method for orally disintegrating tablet of diphenhydramine hydrochloride and caffeine is practical and easy for quality control.

Establishment of determination of tetrodotoxin sustained-release microspheres / 药学实践杂志

Objective To establish a detection method for the determination of tetrodotoxin (TTX) in sustained-release microspheres. Methods The HPLC separation of tetrodotoxin was performed on an Agilent ZORBAX SB-C18 column (4.6mm×150mm,5 μm) with acetonitrile, 8mmol/L sodium heptane sulfonate containing 0.005% TFA (5:95) (pH 4.0) as the mobile phase. The flow rate was 1.0 ml/min. The UV detection wavelength was 200 nm and the column temperature was 30 °C. Results The method had good specificity and linearity of TTX in the concentration range of 1−20 μg/ml. The intra-day precision, inter-day precision, stability and repeatability of the method were good, and the average recoveries were found between 98.0% and 102.0%. Conclusion This study established an HPLC method which was suitable for the determination of tetrodotoxin sustained-release microspheres. The method is accurate and reliable within the applicable range, with strong specificity, which could lead to quantitative detection.

Correlation analysis of asthma and prognosis in 148 children with low immune function / 公共卫生与预防医学

Objective To analyze the effect of immune function on the condition and prognosis of asthma in children with asthma. Methods A total of 148 children with asthma diagnosed in Qinghai women and children's Hospital from January 2018 to January 2021 were included in the analysis, the immune function of the children was determined, and the information of all children was followed up for 6 months after treatment; compared The condition and follow-up prognosis of children with immunocompromised and normal immune function were analyzed and discussed, and the correlation between the expression levels of immunoglobulins (IgG, IgA, IgM) and the condition and short-term recurrence prognosis (6 months) of children was analyzed and discussed, so as to guide Prevention and clinical work. Statistical analysis was done using SPSS19.0. Results The average age of 148 children with recurrent respiratory tract infection in the study was (8.94±3.65) years old, including 70 male children. The condition of the children was evaluated and classified into mild/severe cases: 148 children in this study included mild cases. There were 98 cases and 50 severe cases. There were more males and lower BMI levels in severe children (P<0.05) . The levels of IgG, IgA and IgM in children were all lower in severe children (P<0.05) . The follow-up found that the proportion of relapses in critically ill children was higher (P<0.05). Comparing the levels of IgG, IgA, and IgM in mild and severe children, the average levels of IgG, IgA, and IgM in severe children were lower than those in the mild group, and the difference was statistically significant (P<0.05); recurrence within 6 months of follow-up Prognostic evaluation showed that 19 of the 148 children had relapse, and the levels of IgG, IgA, and IgM in severe relapsed children were significantly lower than those without relapse (P<0.05). Analysis of the relevant factors potentially affecting the prognosis of recurrence showed that gender (female) (OR=1.726) , BMI level (weight loss) (OR=1.613) , IgG expression level factor (low expression) (OR=1.898) , IgA expression Level factor (low expression) (OR=3.509) , IgM expression level factor (low expression) (OR=3.217) and disease factor (severe) (OR=3.619) were potential risk factors, which would increase the risk of poor prognosis. Conclusion The asthma attack in children with immunocompromised immune function is relatively severe, and the short-term recurrence probability is higher, which deserves clinical attention and preventive intervention.

Effects of tumor necrosis factor-alpha/extracellular signal-regulated kinase pathway on migration ability of HaCaT cells and full-thickness skin defects in mice / 中华烧伤杂志

Objective: To investigate the effects of tumor necrosis factor-alpha (TNF-α)/extracellular signal-regulated kinase (ERK) pathway on the migration ability of HaCaT cells and full-thickness skin defects in mice. Methods: The experimental research method was adopted. According to the random number table (the same below), HaCaT cells were divided into the normal oxygen group and the hypoxia group cultured under hypoxia (with oxygen volume fraction of 1%, the same below) condition. After 24 hours of culture, the significantly differentially expressed genes between the 2 groups were screened using the microarray confidence analysis software SAM4.01. The significance of the number of each gene in the signaling pathway was analyzed through the Kyoto encyclopedia of genes and genomes to screen the significantly differentially signaling pathways (n=3). HaCaT cells were cultured for 0 (immediately), 3, 6, 12, and 24 h under hypoxia condition. The secretion level of TNF-α was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 5. HaCaT cells were divided into normal oxygen group, hypoxia alone group, and hypoxia+inhibitor group cultured with FR180204 (an ERK inhibitor) and under hypoxia condition. The cells were cultured for 3, 6, 12, and 24 h. The migration ability of the cells was detected by scratch test (n=12). The expressions of phosphorylated nuclear factor kappa B (p-NF-κB), phosphorylated p38 (p-p38), phosphorylated ERK1/2 (p-ERK1/2), N-cadherin, and E-cadherin in HaCaT cells were detected by Western blotting under hypoxic condition for 0, 3, 6, 12, and 24 h (n=3). Sixty-four BALB/c male mice aged 6 to 8 weeks were used to make a full-thickness skin defect wound model on the dorsum of the mice. The mice were divided into the blank control group and the inhibitor group treated with FR180204, with 32 mice in each group being treated accordingly. On post injury day (PID) 0, 3, 6, 9, 12, and 15, the wound conditions of mice were observed and the healing rate was calculated (n=8). On PID 1, 3, 6, and 15, hematoxylin-eosin staining was used to observe neovascularization, inflammatory cell infiltration, and epidermal regeneration on wound, Masson staining was used to observe collagen deposition on wound, the expressions of p-NF-κB, p-p38, p-ERK12, N-cadherin, and E-cadherin in wound tissue were detected by Western blotting (n=6), the number of Ki67 positive cells and the absorbance value of vascular endothelial growth factor (VEGF) were detected by immunohistochemistry (n=5), the protein expressions of interleukin 6 (IL-6), IL-10, IL-1β, and CCL20 in wound tissue were detected by ELISA (n=6). Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, factorial design analysis of variance, Tukey test, least significant difference test, and independent sample t test. Results: After 24 hours of culture, compared with normal oxygen group, 7 667 genes were up-regulated and 7 174 genes were down-regulated in cells in hypoxic group. Among the above differentially expressed genes, the TNF-α signaling pathway had significant change (P<0.05) with large number of genes. Under hypoxia condition, the expression of TNF-α at 24 h of cell culture was (11.1±2.1) pg/mL, which was significantly higher than (1.9±0.3) pg/mL at 0 h (P<0.05). Compared with normal oxygen group, the migration ability of cells in hypoxia alone group was significantly enhanced at 6, 12, and 24 h of cell culture (with t values of 2.27, 4.65, and 4.67, respectively, P<0.05). Compared with hypoxia alone group, the migration ability of cells in hypoxia+inhibitor group was significantly decreased at 3, 6, 12, and 24 h of cell culture (with t values of 2.43, 3.06, 4.62, and 8.14, respectively, P<0.05). Under hypoxia condition, the expressions of p-NF-κB, p-ERK1/2, and N-cadherin were increased significantly at 12 and 24 h of cell culture compared with 0 h of culture (P<0.05), the expression of p-p38 was significantly increased at 3, 6, 12, and 24 h of cell culture (P<0.05), the expression of E-cadherin was significantly decreased at 6, 12, and 24 h of cell culture (P<0.05), the expression of p-ERK1/2, p-NF-κB, and E-cadherin was time-dependent. Compared with blank control group, on PID 3, 6, 9, 12, and 15, the wound healing rate of mice in inhibitor group was significantly decreased (P<0.05); there were more inflammatory cell infiltration around the wound edge of mice in inhibitor group on PID 3, 6, and 15, especially on PID 15, a large number of tissue necrosis and discontinuous new epidermal layer were observed on the wound surface, and collagen synthesis and new blood vessels were reduced; the expression of p-NF-κB in the wound of mice in inhibitor group was significantly decreased on PID 3 and 6 (with t values of 3.26 and 4.26, respectively, P<0.05) but significantly increased on PID 15 (t=3.25, P<0.05), the expressions of p-p38 and N-cadherin were significantly decreased on PID 1, 3, and 6 (with t values of 4.89, 2.98, 3.98, 9.51, 11.69, and 4.10, respectively, P<0.05), the expression of p-ERK1/2 was significantly decreased on PID 1, 3, 6, and 15 (with t values of 26.69, 3.63, 5.12, and 5.14, respectively, P<0.05), the expression of E-cadherin was significantly decreased on PID 1 (t=20.67, P<0.05) but significantly increased on PID 6 (t=2.90, P<0.05); the number of Ki67 positive cells and absorbance value of VEGF of wound in inhibitor group were significantly decreased on PID 3, 6, and 15 (with t values of 4.20, 7.35, 3.34, 4.14, 3.20, and 3.73, respectively, P<0.05); the expression of IL-10 in the wound tissue of the inhibitor group was significantly decreased on PID 6 (t=2.92, P<0.05), the expression of IL-6 was significantly increased on PID 6 (t=2.73, P<0.05), the expression of IL-1β was significantly increased on PID 15 (t=3.46, P<0.05), and CCL20 expression levels were significantly decreased on PID 1 and 6 (with t values of 3.96 and 2.63, respectively, P<0.05) but significantly increased on PID 15 (t=3.68, P<0.05). Conclusions: The TNF-α/ERK pathway can promote the migration of HaCaT cells, and regulate the healing of full-thickness skin defect wounds in mice by affecting the expression of inflammatory cytokines and chemokines.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats / 中华劳动卫生职业病杂志

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Synthesis and antibacterial activity of synephrine sulfonamide derivatives containing tetrazole and sulfuryl groups / 药学学报

Synephrine is a natural small-molecule alkaloid found in Aurantii fructus immaturus with versatile biological activities, but its derivatives have been rarely studied so far. Based on the multi-target drug design strategy, the phenolic hydroxyl and secondary amino group of synephrine were modified structurally by the molecular splicing method in this study and thus five intermediates and fifteen target molecules were designed and synthesized. These compounds were evaluated with certain human pathogenic bacteria and fungi, and found that the inhibitory activities of IM4 and IM5 against E.coli are comparable to those of eight fluoroquinolones; TM1n showed stronger inhibitory activity against drug-resistant C. trobicans and drug-resistant C. albicans than the positive control drug fluconazole. TM1d and TM1f against C. albicans ATCC90023, TM1o and TM1f against drug-resistant C. albicans, and TM1f against C. parapsilosis ATCC22019 are all comparable to fluconazole, all of which have the potential for in-depth research. In this study, synephrine derivatives with strong inhibitory activities against human pathogenic fungi were discovered for the first time, which provided a new idea for the further study of synephrine.

Risk factors analysis of central airway stenosis after lung transplantation / 器官移植

Objective To investigate the risk factors of central airway stenosis after lung transplantation. Methods Clinical data of 155 recipients undergoing lung transplantation in Wuxi People's Hospital Affiliated to Nanjing Medical University from July 2016 to December 2017 were retrospectively analyzed. According to the incidence of central airway stenosis following lung transplantation, all recipients were divided into the stenosis group (n=36) and control group (n=119). The incidence of central airway stenosis after lung transplantation was summarized. The risk factors of central airway stenosis after lung transplantation were assessed by univariate and multivariate logistic regression analyses. Results Among 155 lung transplant recipients, 36 cases (23.2%) developed central airway stenosis. The average incidence time was (53±13) d after lung transplantation. Univariate analysis demonstrated that bilateral lung transplantation, grade 3 primary graft dysfunction (PGD), airway fungal infection, long cold ischemia time, long mechanical ventilation time and long intensive care unit (ICU) stay were the risk factors for central airway stenosis after lung transplantation (all P < 0.05). Multivariate analysis showed that airway fungal infection, long cold ischemia time and long mechanical ventilation time were the independent risk factors for central airway stenosis after lung transplantation (all P < 0.05). Conclusions Airway fungal infection after lung transplantation, long cold ischemia time and long mechanical ventilation time probably lead to central airway stenosis after lung transplantation. Active preventive measures and intimate monitoring should be taken to improve the quality of life of the recipients after lung transplantation.

Chest high-resolution CT features analysis in predicting the progression of asbestosis / 中华劳动卫生职业病杂志

Objective: To analyze the radiological characteristics of chest high-resolution computed tomography (HRCT) of patients with asbestosis, and to investigate the signs of predicting the disease progression of asbestosis. Methods: A prospective method was used to enroll 68 patients with asbestosis who were regularly followed up from 2013 to 2016. The radiological characteristics of patients with asbestosis were described by the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD) , and the differences between patients with and without progression were compared during the observation period. The Cox proportional hazards regression model was used to analyze the chest HRCT radiological signs predicting the progression of asbestosis. Results: The study included 68 patients with asbestosis aged (65.5±7.8) years old, of which 64.7% (44/68) were female, 29.4% (20/68) had a history of smoking. There was no significant difference in age, sex, smoking and asbestos exposure between patients with progressive asbestosis (20.6%, 14/68) and patients without progressive asbestosis (79.4%, 54/68) (P>0.05) . Chest HRCT of patients with asbestosis showed irregular and/or linear opacities, of which 5.9% (4/68) were accompanied by honeycombing. Irregular and/or linear opacities were mainly lower lung preponderant, often accompanied with ground glass opacity and mosaic perfusion. 98.5% (67/68) had pleural abnormalities, of which 39.7% (27/68) had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. The analysis of multivariable Cox proportional hazard regression showed that the risk of the progression of asbestosis was increased with higher irregular and/or linears opacities cores (HR=1.184, 95%CI: 1.012-1.384, P=0.034) and the appearance of honeycombing (HR=6.488, 95%CI: 1.447-29.097, P=0.015) . Conclusion: The irregular and/or linear opacities scores and honeycombing on chest HRCT are independent influencing factors for predicting the disease progression of asbestosis.

Analysis of influencing factors on surgical outcome and exploration of technical principles during pancreaticojejunostomy / 中华外科杂志

Pancreaticojejunostomy is the most common anastomosis following pancreaticoduodenectomy and middle pancreatectomy. The detailed surgical technics of pancreaticojejunostomy vary dramatically, but none of them can achieve zero fistula rate. In recent years,with the development of new surgical concept,application of new surgical technology, high-tech materials and instruments,the incidence of pancreatic fistula has decreased. At the same time,researches on investigating the risk factors of pancreaticojejunostomy are gradually deepening. Based on years of surgical experience on pancreaticojejunostomy and current literatures, this paper analyzes the factors affecting the effect of pancreaticojejunostomy, such as the patient's basic physical state,pancreatic texture and diameter of the pancreatic duct,pathology and course of the disease,surgical technology and perioperative management,and summarizes six technical principles for pancreaticojejunostomy to be shared with surgical comrades:appropriate tension,protection of blood supply,hermetic closure of pancreatic section,accurate connection of pancreatic duct and intestinal mucosa,individualization,learning and accumulation of experience.

Efficacy of fenestrated atrial septal defect occulders on pulmonary hypertension dogs / 中华心血管病杂志

Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery . Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.

Progress on the mechanism of radiation-induced skin injury / 中国辐射卫生

Skin is the first organ of contact with ionizing radiation. Radiation-induced skin injury is common because the basal cell layer and capillaries of the skin are very sensitive to radiation. Acute radiation-induced skin injury primarily involves cellular alterations and inflammation in the epidermis and dermis, and late skin injury is mainly related to the effect of radiation on blood vessels. Clinical manifestations of radiation-induced skin injury include erythema, dry desquamation, moist desquamation, and ulceration in the skin mucosa, and the severity is related to the type and dose of radiation. Currently, the underlying mechanisms of radiation-induced skin injury are largely unknown, and the gold standard for the treatment of radiation injury has not been established. The known mechanisms of radiation-induced skin injury can be roughly divided into three pathways: oxidative stress injury caused by excessive production of reactive oxygen species, inflammation triggered by transcriptional activation of cytokines, and immune response evoked by bone marrow-derived cells. This paper reviews the three major pathways of mechanisms of radiation-induced skin injury, giving a reference for further mechanism study and preventive treatment of radiation-induced skin injury.

Synthesis and biological activities of three-molecule conjugates with para-aminosalicylic acid as parent nucleus / 药学学报

Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.