OBJECTIVE To investigate the inhibitory effects of formononetin on lipopolysaccharide （LPS）-induced apoptosis and inflammatory response in alveolar epithelial cells through phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS Human lung cancer alveolar basal epithelial cells A549 were cultured in vitro and divided into control group （no intervention）， model group （1 μg/mL LPS）， different concentrations of formononetin groups （1 μg/mL LPS+6.25， 12.5， 25， 50 μmol/L formononetin）. The levels of inflammatory factors （interleukin-8， tumor necrosis factor-α） and cell viability were detected in each group. Another A549 cells were divided into control group， model group （1 μg/mL LPS）， LPS+25 group （1 μg/mL LPS+25 μmol/L formononetin）， inhibitor group （1 μg/mL LPS+20 μmol/L LY294002）， formononetin+inhibitor group （1 μg/mL LPS+25 μmol/L formononetin+20 μmol/L LY294002） and formononetin+activator group （1 μg/mL LPS+25 μmol/L formononetin+ 10 μmol/L SC79）. The secretion levels and mRNA expressions of inflammatory factors， cell apoptosis， and expressions of the key proteins of PI3K/Akt signaling pathway were detected in each group. RESULTS Compared with model group， the levels of inflammatory factors were decreased significantly after the intervention of 25 μmol/L of formononetin， and the cell viability was increased significantly （P＜0.05）. Compared with the control group， the secretion levels and mRNA expressions of inflammatory factors， apoptotic rate， and relative expressions of phosphorylated Akt and phosphorylated PI3K of the model group were increased significantly （P＜0.05）. Compared with the model group， the above indexes of the LPS+25 group and the inhibitor group were decreased significantly （P＜0.05）. Compared with the LPS+25 group， the above indicators of formononetin+inhibitor group were further decreased， while those of formononetin+activator group were increased significantly （P＜0.05）. CONCLUSIONS Formononetin can inhibit LPS-induced epithelial cell apoptosis and improve inflammatory response， and the mechanism may be related to the inhibition of the PI3K/Akt signaling pathway.

INTRODUCTION: Singapore has had three medical schools since 2013. We undertook a cross-sectional quantitative national survey to determine the financial impact of medical education on medical students in Singapore. METHODS: All 1,829 medical students in Singapore were invited to participate in this study. Information on demographics, financial aid utilisation and outside work was collected and analysed. RESULTS: 1,241 (67.9%) of 1,829 students participated in the survey. While the overall proportion of students from households with monthly incomes < SGD 3,000 was only 21.2% compared to the national figure of 31.4%, 85.4% of medical students expected to graduate with debts > SGD 75,000. There were significant differences in per capita incomes among the schools, with 54.5%, 23.3% and 7.8% of Duke-NUS Medical School (Duke-NUS), NUS Yong Loo Lin School of Medicine (NUS Medicine) and Lee Kong Chian School of Medicine (LKCMedicine) students, respectively, reporting a per capita income of < SGD 1,000 (p < 0.001). There were significant differences in financial support: 75.0%, 34.1% and 38.8% of Duke-NUS, NUS Medicine and LKCMedicine students, respectively, received financial aid (p < 0.001). The top reasons for not applying for aid included a troublesome application process (21.4%) and the perception that it would be too difficult to obtain (21.0%). CONCLUSION Students in the three medical schools in Singapore differ in their financial needs and levels of financial support received. A national approach to funding medical education may be needed to ensure that financial burdens do not hamper the optimal training of doctors for Singapore's future.
Cross-Sectional Studies ; Financial Stress ; Humans ; Schools, Medical ; Singapore ; Students, Medical ; Surveys and Questionnaires

Macrolide and corticosteroid resistance has been reported in patients with Mycoplasma pneumoniae (MP) pneumonia (MPP). MP clearance is difficult to achieve through antibiotic treatment in sensitive patients with severe MPP (SMPP). SMPP in children might progress to airway remodeling and even bronchiolitis/bronchitis obliterans. Therefore, identifying serum biomarkers that indicate MPP progression and exploring new targeted drugs for SMPP treatment require urgency. In this study, serum samples were collected from patients with general MPP (GMPP) and SMPP to conduct proteomics profiling. The Fc fragment of the IgG-binding protein (FCGBP) was identified as the most promising indicator of SMPP. Biological enrichment analysis indicated uncontrolled inflammation in SMPP. ELISA results proved that the FCGBP level in patients with SMPP was substantially higher than that in patients with GMPP. Furthermore, the FCGBP levels showed a decreasing trend in patients with GMPP but the opposite trend in patients with SMPP during disease progression. Connectivity map analyses identified 25 possible targeted drugs for SMPP treatment. Among them, a mechanistic target of rapamycin kinase (mTOR) inhibitor, which is a macrolide compound and a cell proliferation inhibitor, was the most promising candidate for targeting SMPP. To our knowledge, this study was the first proteomics-based characterization of patients with SMPP and GMPP.
Biomarkers ; Carrier Proteins ; Child ; Humans ; Immunoglobulin Fc Fragments ; Immunoglobulin G ; Macrolides ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma/drug therapy* ; Proteomics

Objective To investigate the effect of piR-9994 on the biological behavior of gastric cancer cells and its possible mechanism. Methods The expression of piR-9994 in gastric cancer cell lines (MGC803 and AGS) and normal gastric epithelial cells (GES-1) were detected by qRT-PCR. MGC803 cell line with piR-9994 overexpression and knockdown were constructed. The effects of piR-9994 expression changes on cell proliferation were detected by MTT and clone formation assay. The scratch wound healing assay and Transwell invasion assay were used to detect cell migration and invasion abilities. qRT-PCR and Western blot were used to detect cell proliferation and EMT-related genes expression. Results The expression level of piR-9994 in MGC803 cells was significantly higher than that in normal gastric epithelial cell line GES-1 (P < 0.05). The overexpression of piR-9994 promoted the proliferation, invasion and metastasis of gastric cancer cells, while piR-9994 knockdown had the opposite effect. piR-9994 expression was closely related to cell cycle, especially in S phase. The overexpression of piR-9994 promoted the expression of proliferation-related genes PCNA, CCND1 and Bcl-2, inhibited the expression of apoptosis gene C-PARP, and promoted the expression of EMT-related genes N-cadherin, MMP7, Twist and Vimentin; while piR-9994 knockdown had the opposite effect. Conclusion Abnormal expression of piR-9994 affects the proliferation, invasion, metastasis and EMT process of gastric cancer cells. piR-9994 may be a new biomarker and therapeutic target for gastric cancer.

Objective To explore the expression of circ_0006692 in NSCLC and its relation with clinicopathological characteristics and related mechanism. Methods We collected 50 pairs of NSCLC tissues and adjacent tissues. The expression of circ_0006692 was detected by qRT-PCR and its relation with clinicopathological features was analyzed. We constructed lung cancer A549 cell line with circ_0006692 overexpression and knockdown. Cell proliferation, migration and invasion were detected by MTS, colony forming, wound healing and Transwell invasion assays. qRT-PCR and Western blot were used to detect the effect of circ_0006692 expression change on EMT-related gene expression. Results The expression of circ_0006692 in NSCLC was significantly higher than that in adjacent tissues (P < 0.05). The expression level of circ_0006692 was closely related to tumor size, TNM stage and pulmonary membrane invasion (P < 0.05). circ_0006692 knockdown inhibited cell proliferation, invasion and metastasis, while its overexpression promoted cell proliferation, invasion and metastasis. circ_0006692 knockdown inhibited the expression of EMT-related genes CDH2 and MMP7 in A549 cells and promoted the expression of CDH1. Conclusion The upregulated expression of circ_0006692 in NSCLC is closely related to tumor size, TNM stage and pulmonary membrane invasion. circ_0006692 expression could regulate the proliferation, invasion, metastasis and EMT progression of lung cancer A549 cells.

Objective:To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China.Methods:A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ 2 test was used for categorical variables. Results:A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ 2= 6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ2=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ 2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ 2= 4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ 2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ 2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ 2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10 9/L vs. 10.5 (2.5-32.2)×10 9/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L vs. 0.24 (0.01-18.85) μg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions:The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

Objective:To assess the association between visual-related quality of life (QOL) and the severity of quick contrast sensitivity function (qCSF) defects in patients with early cataract.Methods:A cross section design was performed.Ninety-two eyes of 46 patients with early cataract were enrolled in Zhongshan Ophthalmic Center from March to June in 2017.All subjects completed the Chinese version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). The qCSF measurements were performed monocularly and binocularly while the patients wearing full spectacle correction spectacles.Rasch analysis was performed to obtain final NEI VFQ-25 scores.Best corrected visual acuity (BCVA)(LogMAR) was measured and the eye with the better or the worse visual acuity was defined accordingly.The correlation between the Rasch calibrated QOL composite scores and the qCSF measurements of the better eye, the worse eye and binoculus, including the area under Log contrast sensitivity function (AULCSF), qCSF under cut-off frequency and 1.0, 1.5, 3.0, 6.0, 12.0, 18.0 c/d were analyzed.This study protocol was approved by the Ethic Committee of Zhongshan Ophthalmic Center.This study complied with Declaration of Helsinki.Results:The Rasch calibrated QOL composite score was 64.13±4.76.Significant negative correlations were found between composite scores of QOL and the BCVA of both the better or worse eye(the better eye: r=-0.386, P=0.008; the worse eye: r=-0.413, P=0.004). Significant positive correlations were found between the composite scores of QOL and the AULCSF of binoculus, the better and worse eye (binoculus: r=0.531, P<0.001; the better eye: r=0.524, P<0.001; the worse eye: r=0.711, P<0.001); Significant positive correlations were found between the composite scores of QOL and the qCSF under cut-off of binoculus, the better and worse eye (binoculus: r=0.504; the better eye: r=0.419; the worse eye: r=0.694, P<0.01). The composite scores of QOL was positively correlated with the qCSF under 1.5, 3.0, 6.0, 12.0 c/d of binoculus, the better and worse eye (binoculus: r=0.444, 0.544, 0.545, 0.493; all at P<0.05; the better eye: r=0.374, 0.506, 0.530, 0.431; all at P<0.05; the worse eye: r=0.513, 0.679, 0.710, 0.558; all at P<0.05). The composite scores of QOL was positively correlated with the qCSF under 1.0, 18.0 c/d of binoculus and the worse eye (1.0 c/d: r=0.296, 0.292; both at P<0.05; 18.0 c/d: r=0.386, 0.321; both at P<0.05). Conclusions:The qCSF measurements can reflect visual function of patients with early cataract at different spatial frequencies.The qCSF measurements of binoculus, the better eye and the worse eye show significant correlations with the composite scores of QOL.The QOL of early cataract patients shows a strong dependency on the worse eye.

Objective:To explore the effect of traditional Chinese medicine fumigation and washing on the clinical indicators of elderly patients with distal radius fractures after small splint fixation.Methods:From November 2015 to November 2018, 180 elderly patients with fracture of the distal radius in Ningbo Hospital of Traditional Chinese Medicine were selected, and they were divided into control group and observation group according to the random digital table method, with 90 cases in each group.The two groups were given manual reduction and small splint fixation treatment, and the observation group was treated with traditional Chinese medicine fumigation on the basis of the control group therapy.The related inflammatory cytokines in patients plasma and serum viscosity(TNF-α, IL-1, IL-6) were detected, and the clinical curative effect and adverse reactions were observed.Results:Before treatment, there were no statistically significant differences in plasma viscosity and blood inflammatory factors(TNF-α, IL-1, IL-6) between the two groups( t=-0.171, -0.126, 0.483, 0.459, all P>0.05). After treatment, the above indicators in the two groups were significantly lower than those before treatment(observation group: t=38.970, 14.684, 72.258, 53.612; control group: t=20.098, 19.045, 33.962, 34.822, all P<0.05), which in the observation group were lower than those in the control group ( t=-30.239, -7.043, -31.815, -10.359, all P<0.05). The total effective rate of the observation group was 88.88%(80/90), which was higher than 71.11%(64/90) of the control group, the difference was statistically significant between the two groups(χ2=8.889, P<0.05). Conclusion:For the elderly patients with distal radius fracture, the combination of reduction and small splint fixation and fumigation with traditional Chinese medicine can significantly improve the hemorheology of the patients and reduce the contents of inflammatory factors in the body, with significant efficacy and no adverse reactions, which is worthy of clinical application.

Objective:To objectively evaluate the therapeutic effect of Chinese cupping therapy.Method:Near-infrared spectroscopy (NIRS) was used to evaluate the concentration change in oxygenated hemoglobin ([HbO 2]), deoxy-hemoglobin ([Hb]) and blood volume ([tHb]) in 13 healthy volunteers during cupping therapy for the infraspinatus muscle. Results:During the cupping therapy and its pre- and post-treatment period, it was observed that [Hb] and [tHb] in the tissue surrounding the cupping site decreased significantly (both P<0.05), and [HbO 2] increased significantly ( P<0.05), which showed an increase in oxygen uptake. After the cupping was removed, the above hemodynamic changes could still continue for a period of time. Conclusions:Cupping therapy has potential positive therapeutic effects in promoting the hemodynamics for facilitating muscular functions. Functional NIRS surgery has great application potential in the field of physical rehabilitation therapy such as cupping.

Objective To investigate the detection and distribution of hospitalized specimens from a tertiary hospital over 5 years. Methods Specimens of sputum, urine, blood, secretions and puncture fluid were collected from patients admitted to the Harrison International Peace Hospital from November 2013 to November 2018. The origin of specimens, the distribution of departments and the distribution of pathogenic bacteria isolated were analyzed retrospectively. Results A total of 61 286 specimens were sent for examination during the 5 years. The top 5 specimens were sputum culture (n = 18 302, 29.9%), sputum smear (n = 11 253, 18.4%), blood culture (n = 9 713, 15.8%), urine culture (n = 6 448, 10.5%) and secretion culture (n = 6 133, 10.0%), accounting for 84.6% (51 849/61 286). Sputum specimens accounted for 48.2% (29 555/61 286) with the largest proportion. The number of specimens from medical wards was much higher than that from surgical wards (specimens: 25 468 vs. 10 521), respiratory medicine, department of critical care medicine and emergency intensive care unit (EICU) were important sources of pathogenic specimens in the hospital, accounting for 29.8% (18 243/61 286) in total. The average positive rate of all specimens was 23.5% (14 424/61 286). The positive rates of sputum culture and urine culture were 29.7% (5 428/18 302) and 35.4% (2 281/6 448), respectively, while the positive rate of blood culture was only 6.6% (643/9 713). Escherichia coli was the most common pathogen in all specimens except for sputum culture and fecal culture. Escherichia coli [40.6% (926/2 281)], Klebsiella pneumoniae [9.2% (210/2 281)], Pseudomonas aeruginosa [8.2% (188/2 281)], Enterococcus faecalis (group D) [6.6% (151/2 281)] and Candida albicans [3.2% (73/2 281)] were the most common pathogens in urine culture. Klebsiella pneumoniae [24.1% (1 309/5 428)], Acinetobacter baumannii [21.3% (1 154/5 428)], Pseudomonas aeruginosa [15.1% (818/5 428)], Escherichia coli [6.5% (351/5 428)] and Maltose oligotrophomonas maltose [5.8% (316/5 428)] were the most common pathogens in sputum culture. Escherichia coli [36.5% (235/643)], Klebsiella pneumoniae [10.9% (70/643)], Pseudomonas aeruginosa [4.8% (31/643)], Staphylococcus epidermidis [3.4% (22/643)] and Staphylococcus humanis [3.3% (21/643)] were the most common pathogens in blood culture. Conclusion Specimens sent for examination by inpatients are mainly from internal medicine wards, mainly from sputum, blood and urine, and the detected pathogens are mainly Gram-negative bacteria.