[The westward migration of Tongji Medical College during the Anti-Japanese War].

Tongji Medical College began its "education Long March" after the Battle of Shanghai in 1937, with six westward migrations across almost 10,000 kilometers over eight years. It first moved to the city of Shanghai because Tongji Medical College had to rent space in Shanghai, then moved to Jinhua in Zhejiang Province soon afterwards. After that it migrated to Ganzhou and Jian in Jiangxi Province, then He County in Guangxi Province and Kunming in Yunnan Province, ultimately locating in Li Village in Sichuan Province. Tongji Medical College was operated by Chinese and implemented high-level administration and teaching under the difficult conditions during the Anti-Japanese War. As a result, Tongji Medical College made advances in the medical field, such those by Professor Wu Mengchao. It also made advancements in research and treatment, such as identifying pathogenesis of a local epidemic and offering some treatment methods, and popularised medical knowledge for local people by exhibitions and news paper columns. It also established the Number One and the Number Five UMC Trauma Centre, participating in battlefield treatment. The German teachers of Tongji Medical College, who did not move to the west, established a German Medical School in Shanghai. Tongji Medical College returned back to Shanghai, incorporating the German Medical School in Shanghai after the Anti-Japanese War.

[The early graduates from Tongji Medical University(1912-1955)].

The early history of Tongji Medical University can be demonstrated from the graduate certification and the photos of graduates from the Tongji Deutsch Medical School in 1912 to the Wuhan Medical College in 1955. It was found that the names, the chancellors and the affiliations of the university kept changing based on the changing of the names, stamps and signatures of the chancellors on the graduate certificates. It was also found that the apparent morale among graduates appeared to be different during different historical stages in graduate photos. Both graduate certificates and graduate photos show the educational achievements by the Tongji Medical University.

[A multicentric study on clinical characteristics and antibiotic sensitivity in children with methicillin-resistant Staphylococcus aureus infection].

Objective: To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus (MRSA) infection and the antibiotic sensitivity of the isolates. Methods: The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children's hospitals in Infectious Diseases Surveillance of Paediatrics (ISPED) group of China between January 1, 2018 and December 31, 2018 were collected retrospectively. The children's general condition, high-risk factors, antimicrobial therapy and prognosis, differences in clinical disease and laboratory test results between different age groups, and differences of antibiotic sensitivity between community-acquired (CA)-MRSA and hospital-acquired (HA)-MRSA were analyzed. The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates. Results: Among the 452 patients, 264 were males and 188 were females, aged from 2 days to 17 years. There were 233 cases (51.5%) in the ≤1 year old group, 79 cases (17.5%) in the>1-3 years old group, 29 cases (6.4%) in the >3-5 years old group, 65 cases (14.4%) in the >5-10 years old group, and 46 cases (10.2%) in the>10 years old group. The main distributions of onset seasons were 55 cases (12.2%) in December, 47 cases (10.4%) in February, 46 cases (10.2%) in November, 45 cases (10.0%) in January, 40 cases (8.8%) in March. There were 335 cases (74.1%) CA-MRSA and 117 (25.9%) cases HA-MRSA. Among all cases, 174 cases (38.5%) had basic diseases or long-term use of hormone and immunosuppressive drugs. During the period of hospitalization, 209 cases (46.2%) received medical interventions. There were 182 patients (40.3%) had used antibiotics (ß-lactams, glycopeptides, macrolides, carbapenems, oxazolones, sulfonamides etc) 3 months before admission. The most common clinical disease was pneumonia (203 cases), followed by skin soft-tissue infection (133 cases), sepsis (92 cases), deep tissue abscess (42 cases), osteomyelitis (40 cases), and septic arthritis (26 cases), suppurative meningitis (10 cases). The proportion of pneumonia in the ≤1 year old group was higher than the >1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group (57.5% (134/233) vs. 30.4% (24/79), 31.0% (9/29), 38.5% (25/65), 23.9% (11/46), χ(2)=17.374, 7.293, 7.410, 17.373, all P<0.01) The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA (33.4% (112/335) vs. 17.9% (21/117), χ(2)=10.010, P=0.002), and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA (53.0% (62/117) vs. 42.1% (141/335), χ(2)=4.166, P=0.041). The first white blood cell count of the ≤1 year old group was higher than that children > 1 year old ((15±8)×10(9)/L vs. (13±7)×10(9)/L, t=2.697, P=0.007), while the C-reactive protein of the ≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group (8.00 (0.04-194.00) vs.17.00 (0.50-316.00), 15.20 (0.23-312.00), 21.79(0.13-219.00) mg/L, Z=3.207, 2.044, 2.513, all P<0.05), there were no significant differences in procalcitonin (PCT) between different age groups (all P>0.05). After the treatment, 131 cases were cured, 278 cases were improved, 21 cases were not cured, 12 cases died, and 10 cases were abandoned. The 452 MRSA isolates were all sensitive to vancomycin (100.0%), linezolid (100.0%), 100.0% resistant to penicillin, highly resistant to erythromycin (85.0%, 375/441), clindamycin (67.7%, 294/434), less resistant to sulfonamides (5.9%, 23/391), levofloxacin (4.5%, 19/423), gentamicin (3.2%, 14/438), rifampicin (1.8%, 8/440), minocycline (1.1%, 1/91). The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups (all P>0.05). Conclusions: The infection of MRSA is mainly found in infants under 3 years old. The prevalent seasons are winter and spring, and MRSA is mainly acquired in the community. The main clinical diseases are pneumonia, skin soft-tissue infection and sepsis. No MRSA isolate is resistant to vancomycin, linezolid. MRSA isolates are generally sensitive to sulfonamides, levofloxacin, gentamicin, rifampicin, minocycline, and were highly resistant to erythromycin and clindamycin. To achieve better prognosis. clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.

[A century of memory of Tongji Medical College: Selected collections from Museum of History].

This paper presents a harsh course of Tongji Medical School.The school was relocated several times, but still kept running though it met with the cataclysm-the World WarⅠand World WarⅡ.By using collections from School History Museum of Huazhong University of Science and Technology and Hospital History Museum of Tongji Medical School as clue and combining the years of itself, it's found that Tongji Medical School is a medical education institution which has Germanic medical educational tradition. The information from this paper has provided the primary sources for research on the origin and development of modern Chinese medical education.

[Biography of Chen Zi].

Chen Zi(1878-1927), who also styled himself as "Yi Qing" or "Yi Qin" , was a famous ophthalmologist in the early period of the Republic of China.He compiled and translated serial of classical Japanese modern medical books thus promoted western medicine propagation to the east in the early period of the Republic of China, and founded the first Chinese-established eye hospital in China to serve the patients from Shanghai as well as other places in China.Also, Dr. Chen devoted himself to the combination of traditional Chinese medicine and Western medicine for his whole life.He wrote the book of Zhong Xi Yan Ke Hui Tong(, Combination of Western and Eastern Medicine in Ophthalmology)which has promoted traditional Chinese medicine into modernization.In Dr.Chen's life, he was associated with some figures from army and in political circles at that time. Besides, he did a lot of things to support the education in his hometown.Dr. Chen was a typical model to understand the clinical doctors in the early period of the Republic of China.

[A multicentric clinical study on clinical characteristics and drug sensitivity of children with pneumococcal meningitis in China].

Objective: To understand clinical characteristics of children with pneumococcal meningitis (PM) in China and to analyze the drug sensitivity of Streptococcus pneumoniae isolates and associated impacts on death and sequelae. Methods: The clinical data, follow-up results and antimicrobial sensitivity of isolated strains of 155 children (including 98 males and 57 females, age ranged from 2 months to 15 years) with PM in 10 tertiary-grade A class hospitals of Infectious Diseases Surveillance of Pediatrics (ISPED) from 2013 to 2017 were collected and analyzed retrospectively. Patients were divided into different groups according to the following standards: ≤1 year old group,>1-3 years old group and >3 years old group according to age; death group and non-death group according to the death within 30 days after PM diagnosis; complication group and non-complication group according to the abnormal cranial imaging diagnosis; sequelae group and no-sequelae group according to the follow-up results. Bonfereoni chi-square segmentation and Kruskal-Wallis H test were used for statistical analysis. Results: There were 64 cases (41.3%) in the ≤1 year old group, 39 cases in the >1-3 years old group (25.2%), and 52 cases (33.5%) in the >3 years old group. The most common clinical manifestation was fever (151 cases, 97.4%). The mortality was 16.8% (26/155) during hospitalization. The neurological complication rate was 49.7% (77/155) during hospitalization, including the most common complication, subdural effusion and (or) empyema in 50 cases (32.3%) and hearing impairment in 6 cases. During follow-up after discharge, no death was found and focal neurological deficits were found in 47 cases (30.3%), including the frequent neurological sequelae: cognitive and mental retardation of different degree in 22 cases and hearing impairment in 14 cases (9.0%). The rate of cure and improvement on discharge was 74.8% (116/155) and the lost to follow-up rate was 8.4% (13/155). The proportions of died cases, neurological complications during hospitalization and proportions of peripheral white blood cell count <12 × 10(9)/L before admission in ≤1 year old group were significantly higher than those in >3 years old group (25.0% (16/64) vs. 5.8% (3/52), 75.0% (48/64) vs. 25.0% (13/52), 48.4% (31/64) vs. 15.4% (8/52), χ(2)=7.747, 28.767, 14.044; P=0.005, 0.000, 0.000). The proportions of headache, vomiting, neck resistance and high risk factors of purulent meningitis in >3 years old group were significantly higher than those in ≤ 1 year old group (67.3%(35/52) vs. 1.6%(1/64), 80.8% (42/52) vs. 48.4% (31/64), 69.2% (36/52) vs. 37.5% (24/64), 55.8% (29/52) vs. 14.1%(9/64), χ(2)=57.940, 12.856, 11.568, 22.656; P=0.000, 0.000, 0.001, 0.000). Streptococcus pneumoniae isolates were completely sensitive to vancomycin (100.0%, 152/152), linezolid (100.0%, 126/126), moxifloxacin (100.0%, 93/93) and ofloxacin (100.0%,41/41); highly sensitive to levofloxacin (99.3%, 142/143) and ertapenem (84.6%, 66/78); moderately sensitive to ceftriaxone (48.4%, 45/93), cefotaxime (40.0%, 44/110) and meropenem (38.0%, 38/100); less sensitive to penicillin (19.6%, 27/138) and erythromycin (4.2%, 5/120). The proportions of non-sensitive strains of penicillin (21/21) and meropenem (17/18) in the death group were significantly higher than those (90/117, 45/82) in the survived group(χ(2)=4.648 and 9.808, P=0.031 and 0.002). Conclusions: The children's PM is mainly found in infants under 3 years old in China. Death and neurological complications are more common in PM children under 1 year old. The clinical manifestations and peripheral blood inflammatory markers of PM patients under 1 year old are not typical. Fever is the most common clinical manifestation and subdural effusion and (or) empyema is the most common complication. Long-term hearing impairment is common in PM and the follow-up time must be prolonged. The dead PM cases had high in sensitive rates to penicillin and meropenem.

[Comparison of efficacy between sorafenib and sunitinib as first-line therapy for metastatic renal cell carcinoma and analyze prognostic factors for survival].

Objective: To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival. Methods: The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients' overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models. Results: The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (P=0.325) or DCR (P=0.408). The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome (6.7%), diarrhea (2.3%), and rash (2.3%). The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia (6.2%), hand-foot syndrome (6.2%), and thrombocytopenia (4.6%). During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months (95% CI: 9-15 months), and the median OS was 25 months (95% CI: 21-29 months) in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months (95% CI: 10-12 months) and the median OS was 23 months (95% CI: 20-32 months) in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS (P=0.771) or OS (P=0.548). Multivariate analysis showed Fuhrman grades (HR=1.358, 95%CI: 1.004-1.835), number of metastatic sites (HR=1.550, 95%CI: 1.143-2.101) and MSKCC risk grade (Intermediate risk group: HR=1.621, 95%CI: 1.117-2.232; Poor risk group: HR=2.890, 95%CI: 1.942-4.298) were independent prognostic factors for PFS. Fuhrman grades (HR=2.135, 95%CI: 1.533-2.974), number of metastatic sites (HR=1.774, 95%CI: 1.279-2.461) and MSKCC risk grade (Intermediate risk group: HR=1.415, 95%CI: 1.002-1.998; Poor risk group: HR=3.161, 95%CI: 2.065-4.838) were independent prognostic factors for OS. Conclusions: The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.

[Tea consumption and the risk of lung cancer in Chinese males: a prospective cohort study].

Objective: To investigate the association between tea consumption and lung cancer risk in Chinese males. Methods: Tea consumption and incident lung cancer cases were collected on a biennial basis among males in Kailuan Cohort during 2006-2015. Up to 31st December 2015, a total of 103 010 male candidates from the Chinese Kailuan Male Cohort Study were enrolled in the present study. Cox proportional hazards regression model was used to evaluate the association between tea consumption and risk of lung cancer in males. Results: The age of male candidates was (51.3±13.4)years old. There were 828 810.74 person-years of follow-up and 8.91 years of median follow-up period. During the follow-up, 964 lung cancer cases were identified. In male, the rate of never cosumers, tea drinkers (<4/week) and tea drinkers (≥4/week) were 58.17%(n=59 926), 24.04%(n=24 765) and 17.78%(n=18 319), respectively. After adjustment for potential confounding factors, HR (95%CI) of lung cancer for subjects with tea drinkers (<4/week) and tea drinkers (≥4/week) were 0.80 (0.63-1.02) and 1.02 (0.80-1.30), respectively, as compared with never cosumers. The results showed no significant association with lung cancer. Stratification analysis and sensitivity analysis showed no significant changes. Conclusion: Our study has not found that tea consumption is significantly associated with the risk of male lung cancer.

Utilization of Western medicine and traditional Chinese medicine among patients with Alzheimer's disease in Taiwan: a nationwide population-based study.

BACKGROUND AND PURPOSE: Large-scale studies of utilization of medical services among patients with Alzheimer's disease (AD) are lacking. We aimed to investigate the usage of Western medicine and traditional Chinese medicine (TCM) among these patients in Taiwan. METHODS: We analyzed one million samples from the National Health Insurance Research Database in Taiwan. Patients (n = 1814) newly diagnosed with AD in 2001-2010 were divided into TCM users (n = 528) and non-TCM users (n = 1286). RESULTS: Compared with non-TCM users, TCM users were younger, had a higher female:male ratio and higher utilization rate of Western medicine. The median interval between diagnosis and the first TCM consultation was 7.92 months. Donepezil and rivastigmine were commonly prescribed medications. Chinese herbal medicine was the most popular treatment among TCM users. CONCLUSIONS: This study revealed the specific usage patterns of TCM and non-TCM medical services among patients with AD. The information could be used for improving the healthcare of patients with AD.

Dexamethasone alone vs in combination with transcutaneous electrical acupoint stimulation or tropisetron for prevention of postoperative nausea and vomiting in gynaecological patients undergoing laparoscopic surgery.

BACKGROUND: Postoperative nausea and vomiting (PONV) is commonly reported after surgery and anaesthesia. We compared the effects of combinations of electrical acupoint stimulation or tropisetron with dexamethasone with the effects of dexamethasone alone, for inhibition of PONV in gynaecological patients undergoing laparoscopic surgery. METHODS: We randomized 157 patients undergoing elective gynaecological laparoscopic surgery under general anaesthesia into the following three groups: acupoint stimulation+dexamethasone (Group Acu, n=53), tropisetron+dexamethasone (Group Trp, n=53), and dexamethasone alone (Group Dxm, n=51). The incidence of nausea, vomiting, and need for rescue antiemetics was recorded 2, 6, 24, and 48 h after surgery. RESULTS: We found significant differences in the incidence of PONV during 24 h after surgery between the combination therapy groups and the dexamethasone-alone group (P=0.021). In the first 24 h, 28% of patients in Group Acu, 26% of patients in Group Trp, and 50% of patients in Group Dxm experienced nausea, vomiting, or both. The incidence of 24 h PONV in Group Acu was significantly lower than that in Group Dxm (P=0.048; odds ratio 0.389; 95% CI 0.170-0.891). The incidence of 24 h PONV in Group Trp was also significantly lower than that in Group Dxm (P=0.042; odds ratio 0.359; 95% CI 0.157-0.819). There was no significant difference between Group Acu and Group Trp (P=0.857). The need for antiemetic rescue medication was similar in the three groups. All groups expressed similar patient satisfaction. CONCLUSIONS: Combined with dexamethasone, electrical acupoint stimulation or tropisetron is more effective in PONV prophylaxis than dexamethasone alone in gynaecological patients undergoing laparoscopic surgery. CLINICAL TRIAL REGISTRATION: NCT 02096835.

Cloning and analysis of the soybean MEKK gene.

In this paper, homologous cloning methods were used to clone the soybean GmMEKK gene, which possesses a high degree of similarity to Arabidopsis thaliana AtMEKK1. AtMEKK1 is formed by 595 amino acids, and its secondary structure is formed by 38 irregular curls, 24 α helix, 14 ß, with S-TKc domain, transmembrane domain and does not have membrane spanning domain and signal peptide. GmMEKK-GFP subcellular localization fusion and prokaryotic expression vectors were generated and it was revealed that GmMEKK encodes a highly conserved 66.8-kDa nuclear protein that is expressed in soybean roots, stem floral pieces, and leaves. A real-time quantitative PCR analysis of GmMEKK under different abiotic stresses revealed that the expression level of GmMEKK increased under drought and low phosphorus and nitrogen conditions. Taken together, these data suggest that GmMEKK may play an important role in the soybean abiotic stress response.

Uranium and thorium leached from uranium mill tailing of Guangdong Province, China and its implication for radiological risk.

The paper focused on the leaching behaviour of uranium (U) and thorium (Th) from uranium mill tailing collected from the Uranium Mill Plant in Northern Guangdong Province, China. Distilled water (pH 6) and sulphuric acid solution (pH 4 and 3) were used as solvent for the leaching over 22 weeks. It was found that the cumulative leach fraction from the mill tailing was 0.1, 0.1 and 0.7 % for U release, and overall 0.01 % for Th release, using distilled water, sulphuric acid solution of pH 4 and pH 3 as leaching agents, respectively. The results indicate that (1) the release of U and Th in uranium mill tailing is a slow and long-term process; (2) surface dissolution is the main mechanism for the release of U and Th when sulphuric acid solution of pH 3 is employed as the leaching agent; (3) both U and Th are released by diffusion when using sulphuric acid solution of pH 4 as the leaching agent and (4) U is released by surface dissolution, while Th is released by diffusion when using distilled water as the leaching agent. The implication for radiological risk in the real environment was also discussed.

Targeted gene silencing to induce permanent sterility.

A non-surgical method to induce sterility would be a useful tool to control feral populations of animals. Our laboratories have experience with approaches aimed at targeting brain cells in vivo with vehicles that deliver a payload of either inhibitory RNAs or genes intended to correct cellular dysfunction. A combination/modification of these methods may provide a useful framework for the design of approaches that can be used to sterilize cats and dogs. For this approach to succeed, it has to meet several conditions: it needs to target a gene essential for fertility. It must involve a method that can selectively silence the gene of interest. It also needs to deliver the silencing agent via a minimally invasive method. Finally, the silencing effect needs to be sustained for many years, so that expansion of the targeted population can be effectively prevented. In this article, we discuss this subject and provide a succinct account of our previous experience with: (i) molecular reagents able to disrupt reproductive cyclicity when delivered to regions of the brain involved in the control of reproduction and (ii) molecular reagents able to ameliorate neuronal disease when delivered systemically using a novel approach of gene therapy.

Applying gene silencing technology to contraception.

Population control of feral animals is often difficult, as it can be dangerous for the animals, labour intensive and expensive. Therefore, a useful tool for control of animal populations would be a non-surgical method to induce sterility. Our laboratories utilize methods aimed at targeting brain cells in vivo with vehicles that deliver a payload of either inhibitory RNAs or genes intended to correct cellular dysfunction. A useful framework for design of a new approach will be the combination of these methods with the intended goal to produce a technique that can be used to non-invasively sterilize cats and dogs. For this approach to succeed, it has to meet several conditions: the target gene must be essential for fertility; the method must include a mechanism to effectively and specifically silence the gene of interest; the method of delivering the silencing agent must be minimally invasive, and finally, the silencing effect must be sustained for the lifespan of the target species, so that expansion of the population can be effectively prevented. In this article, we discuss our work to develop gene silencing technology to induce sterility; we will use examples of our previous studies demonstrating that this approach is viable. These studies include (i) the use of viral vectors able to disrupt reproductive cyclicity when delivered to the regions of the brain involved in the control of reproduction and (ii) experiments with viral vectors that are able to ameliorate neuronal disease when delivered systemically using a novel approach of gene therapy.

The role of fluoroquinolones in the management of urinary tract infections in areas with high rates of fluoroquinolone-resistant uropathogens.

Fluoroquinolones have been recommended as the drugs of choice for the empirical treatment of uncomplicated and complicated urinary tract infections (UTIs) caused by trimethoprim-sulfamethoxazole-resistant uropathogens. However, because of the increased use of both oral and parenteral fluoroquinolones for other kinds of infections, increasing rates of resistance to fluoroquinolones among the most common uropathogens have challenged this recommendation, particularly in the Asia-Pacific region. The current interpretative criteria for the in vitro susceptibility of uropathogens to some fluoroquinolones, such as levofloxacin and ciprofloxacin, are set according to their therapeutic efficacy for bloodstream infections, and are not specific to UTIs. Fluoroquinolones exhibit concentration-dependent antibacterial activity, high renal excretion, and relatively early and prolonged urinary bactericidal titers. Whether or not current interpretative criteria for the in vitro susceptibility of uropathogens to fluoroquinolones predict clinical failure in treating UTIs is still controversial. The Clinical and Laboratory Standards Institute (CLSI) has established UTI-specific breakpoints for resistance to a few fluoroquinolones. However, the application of high-dose fluoroquinolone therapy for the treatment of mild to moderate UTIs caused by isolates with higher minimum inhibitory concentrations (MICs) of several fluoroquinolones needs to be re-validated based on more relevant clinical studies, prudent pharmacokinetic/pharmacodynamic (PK/PD) considerations, and thorough study of the mutant prevention concentration of fluoroquinolones in the treatment of UTI.

Clinical and microbiological characteristics of infections caused by various Nocardia species in Taiwan: a multicenter study from 1998 to 2010.

This multicenter study in Taiwan investigated the clinical presentations of various Nocardia species infections based on 16S rRNA sequence analysis. Patients with nocardiosis in four large medical centers from 1998 to 2010 were included. A total of 100 preserved nonduplicate isolates causing human infection were identified as Nocardia species. Sequencing analysis of 16S rRNA confirmed that 35 of 36 N. asteroides isolates identified by conventional tests were non-asteroides Nocardia species, and that two of 50 N. brasiliensis isolates had also been initially misidentified. N. brasiliensis (50%) was the most common pathogen, followed by N. cyriacigeorgica (18%). In addition, several rare pathogens were identified, including N. asiatica, N. rhamnosiphila, N. abscessus, N. transvalensis, N. elegans, and N. carnea. Primary cutaneous infection was the most common presentation, noted in 55 (55%) patients, while pulmonary infection presented in 26 (26%) patients. The crude mortality rate was 6.7% (6/89), and was lowest for primary cutaneous infection (2.2%) and highest for disseminated disease and pulmonary infection (16.7%). In conclusion, N. brasiliensis and N. cyriacigeorgica were the most common pathogens causing nocardiosis in Taiwan. Molecular methods for identifying Nocardia to the species level are mandatory for better understanding the epidemiology and clinical characteristics of patients with nocardiosis.

Characterization of three diaminopyrimidines as potent and selective antagonists of P2X3 and P2X2/3 receptors with in vivo efficacy in a pain model.

BACKGROUND AND PURPOSE: P2X3 and P2X2/3 receptors are highly localized on the peripheral and central pathways of nociceptive signal transmission. The discovery of A-317491 allowed their validation as chronic inflammatory and neuropathic pain targets, but this molecule has a very limited oral bioavailability and CNS penetration. Recently, potent P2X3 and P2X2/3 blockers with a diaminopyrimidine core group and better bioavailability were synthesized and represent a new opportunity for the validation of P2X3-containing receptors as targets for pain. Here we present a characterization of three representative diaminopyrimidines. EXPERIMENTAL APPROACH: The activity of compounds was evaluated in intracellular calcium flux and electrophysiological recordings from P2X receptors expressed in mammalian cells and in a in vivo model of inflammatory pain (complete Freund's adjuvant (CFA) in rat paws). KEY RESULTS: Compound A potently blocked P2X3 (pIC(50)= 7.39) and P2X2/3 (pIC(50)=6.68) and showed no detectable activity at P2X1, P2X2, P2X4 and P2X7 receptors (pIC(50)< 4.7). Whole-cell voltage clamp electrophysiology confirmed these results. Compounds showed good selectivities when tested against a panel of different classes of target. In the CFA model, compound B showed significant anti-nociceptive effects (57% reversal at 3mg·kg(-1) ). CONCLUSIONS AND IMPLICATIONS: The diaminopyrimidines were potent and selective P2X3 and P2X2/3 receptor antagonists, showing efficacy in vivo and represent useful tools to validate these receptors as targets for inflammatory and neuropathic pain and provide promising progress in the identification of therapeutic tools for the treatment of pain-related disorders.

Cucurbitacin IIa: a novel class of anti-cancer drug inducing non-reversible actin aggregation and inhibiting survivin independent of JAK2/STAT3 phosphorylation.

BACKGROUND: Cucurbitacin (Cuc) and triterpene-derived natural products exhibit anti-cancer potential in addition to their conspicuous anti-bacterial and anti-inflammatory activity. Recently, inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling was shown to underlie the effects of Cuc family on inducing cell death in cancer. METHOD: We purified Cuc IIa, the active component from the medicinal plant Hemsleya amalils Diels, which shows different structural modifications from other Cuc derivatives. We investigated the mechanisms of its inhibitory effects on cancer cells in vitro and tumour growth in vivo. RESULTS: Cuc IIa induced the irreversible clustering of filamentous actin and arrested cell cycle by the increases in G2/M populations. Cuc IIa resulted in the reduced phospho-Histone H3 and markedly increased cleavage of poly-(ADP-ribose) polymerase or PARP, immediate upstream of DNA breakdown as the result of caspase activation, consistent with mitotic blockage-induced cell death. However, unlike other Cuc members, Cuc IIa did not suppress JAK2/STAT3 phosphorylation or alter phosphorylation of mitogen-activated protein kinases. Instead, the expression of the cell cycle-regulated Inhibitor of Apoptosis Protein (IAP) survivin was reduced. Introducing oncoprotein δ-catenin, which increased survivin expression and suppressed small GTPase RhoA, reduced efficacy of Cuc IIa to induce cell death. Supporting the effects of Cuc IIa on actin cytoskeletal signaling, RhoA phosphorylation was reduced suggesting its increased activity. CONCLUSION: Cuc IIa is a novel class of anti-cancer drug in suppression of cancer cell expansion by disrupting the actin cytoskeleton and directing the cell to undergo PARP-mediated apoptosis through the inhibition of survivin downstream of JAK2/STAT3.

Suppression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes.

AIMS: This study investigated the effects of indole-3-carbinol (I3C), a compound from cruciferous vegetables, on various parameters related to obesity, in particular, the parameters of infiltration by macrophages and of inflammatory cytokines expressed during the co-culture of adipocytes and macrophages. METHODS: Male C57BL/6 mice were fed with a control diet (C group), high-fat diet (HF group) and HF+5 mg kg(-1) I3C (HFI group). The I3C was intraperitoneally injected (HFI group) for 12 weeks. Epididymal adipose tissue (AT) was collected and stained for F4/80, a marker of macrophages. RESULTS: The immunohistochemical staining for F4/80 indicated a greater presence of macrophages in the HF group than in AT from the control and HFI groups. Furthermore, I3C treatment, in an in vitro cell culture system, decreased expression of inducible nitric oxide synthase (iNOS), decreased nitrite content and enhanced expression of peroxisome proliferator-activated receptor (PPAR-γ). Moreover, in vitro cell culture studies revealed that I3C inhibited intracellular lipid accumulation in hypertrophied adipocytes. In macrophage and primary adipocyte co-culture, I3C inhibited expression of interleukin-6 (IL-6). CONCLUSIONS: In vivo treatment with I3C reduced the infiltration of macrophages in AT, and in vitro addition of I3C to co-cultured macrophages and adipocytes reduced nitrite production and IL-6 expression. With cultures of adipocytes only, I3C inhibited accumulation of intracellular lipid, either by disrupting differentiation, or by directly inhibiting triglyceride synthesis.

Increased risk of adverse pregnancy outcomes for hospitalisation of women with lupus during pregnancy: a nationwide population-based study.

OBJECTIVES: Using a nationwide population-based dataset to examine the risk of adverse pregnancy outcomes in women with systemic lupus erythematosus (SLE), with and without SLE hospitalisation during pregnancy. METHODS: We identified 1,010 pregnant women who had SLE during 2001 2003 as the study cohort and 5,050 randomly selected pregnant women (five for every woman with SLE) as a comparison cohort. Conditional logistic regression analyses were performed to explore the relationship between women with and without SLE and the risk of low birth weight (LBW), preterm birth, and babies small for gestational age (SGA), after adjusting for the characteristics of the infant, mother, and father. RESULTS: We found that there were significant differences in the risk of LBW (14.9% vs. 7.2%), preterm birth (14.4% vs. 8.5%), and SGA (28.5% vs. 17.5%) for women with SLE compared to women without. In addition, the adjusted odds of LBW, preterm birth, and SGA babies for women who had SLE during pregnancy were 6.15 (95% CI=4.15-9.13), 4.19 (95% CI=2.77-6.36), and 4.25 (95% CI=2.95-6.11) times, respectively, compared to women without any chronic illness. The adjusted odds of LBW, preterm birth, and SGA babies for women who had SLE but were not hospitalized during pregnancy were 1.80 (95% CI=1.43-2.26), 1.62 (95% CI=1.30-2.03), and 1.63 (95% CI=1.38-1.94) times, respectively, compared to unaffected mothers. CONCLUSIONS: We conclude that SLE can impact the pregnancy outcomes, especially if hospitalisation occurs during the pregnancy.