Clinical findings in 111 cases of influenza A (H7N9) virus infection.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Activation of propane C-H and C-C bonds by gas-phase Pt atom: a theoretical study.

The reaction mechanism of the gas-phase Pt atom with C(3)H(8) has been systematically investigated on the singlet and triplet potential energy surfaces at CCSD(T)//BPW91/6-311++G(d, p), Lanl2dz level. Pt atom prefers the attack of primary over secondary C-H bonds in propane. For the Pt + C(3)H(8) reaction, the major and minor reaction channels lead to PtC(3)H(6) + H(2) and PtCH(2) + C(2)H(6), respectively, whereas the possibility to form products PtC(2)H(4) + CH(4) is so small that it can be neglected. The minimal energy reaction pathway for the formation of PtC(3)H(6) + H(2), involving one spin inversion, prefers to start at the triplet state and afterward proceed along the singlet state. The optimal C-C bond cleavages are assigned to C-H bond activation as the first step, followed by cleavage of a C-C bond. The C-H insertion intermediates are kinetically favored over the C-C insertion intermediates. From C-C to C-H oxidative insertion, the lowering of activation barrier is mainly caused by the more stabilizing transition state interaction ΔE(≠) (int), which is the actual interaction energy between the deformed reactants in the transition state.

Theoretical study on the gas-phase reaction mechanism between palladium monoxide and methane.

The gas-phase reaction mechanism between palladium monoxide and methane has been theoretically investigated on the singlet and triplet state potential energy surfaces (PESs) at the CCSD(T)/AVTZ//B3LYP/6-311+G(2d, 2p), SDD level. The major reaction channel leads to the products PdCH(2) + H(2)O, whereas the minor channel results in the products Pd + CH(3)OH, CH(2)OPd + H(2), and PdOH + CH(3). The minimum energy reaction pathway for the formation of main products (PdCH(2) + H(2)O), involving one spin inversion, prefers to start at the triplet state PES and afterward proceed along the singlet state PES, where both CH(3)PdOH and CH(3)Pd(O)H are the critical intermediates. Furthermore, the rate-determining step is RS-CH(3) PdOH → RS-2-TS1cb → RS-CH(2)Pd(H)OH with the rate constant of k = 1.48 × 10(12) exp(-93,930/RT). For the first C-H bond cleavage, both the activation strain ΔE(≠)(strain) and the stabilizing interaction ΔE(≠)(int) affect the activation energy ΔE(≠), with ΔE(≠)(int) in favor of the direct oxidative insertion. On the other hand, in the PdCH(2) + H(2) O reaction, the main products are Pd + CH(3)OH, and CH(3)PdOH is the energetically preferred intermediate. In the CH(2)OPd + H(2) reaction, the main products are Pd + CH(3)OH with the energetically preferred intermediate H(2)PdOCH(2). In the Pd + CH(3)OH reaction, the main products are CH(2)OPd + H(2), and H(2)PdOCH(2) is the energetically predominant intermediate. The intermediates, PdCH(2), H(2) PdCO, and t-HPdCHO are energetically preferred in the PdC + H(2), PdCO + H(2), and H(2)Pd + CO reactions, respectively. Besides, PdO toward methane activation exhibits higher reaction efficiency than the atom Pd and its first-row congener NiO.

[Safety and efficacy of three-dimensional conformal radiotherapy combined with temozolomide in treatment of diffuse brainstem gliomas].

OBJECTIVE: To study the safety and efficacy of three-dimensional conformal radiotherapy in combination with temozolomide in treatment of patients with diffuse brainstem glioma. METHODS: Twelve patients with MRI-confirmed diffuse brainstem glioma received 54 Gy three-dimensional conformal radiotherapy for 6 weeks with 1.8 Gy per fraction, 5 times per week. All of the patients were given daily oral temozolomide 75 mg/m(2) during radiotherapy. Four weeks after radiotherapy, all of the patients received 6 cycles of temozolomide, each cycle lasted 5 days with 28 days interval between each two cycles. 150 mg/m(2) of temozolomide was given for the first cycle for five days, followed by 200 mg/m(2) of the drug for the rest of the cycles if no significant drug-related toxicities were observed. Magnetic resonance imaging and laboratory tests were performed to evaluate the efficacy and adverse reactions. RESULTS: In the 12 patients, CR was 1 case (8.3%), PR 6 cases (50.0%), SD 2 cases (16.7%), and PD 3 cases (25.0%). The overall clinical benefit rate was 75.0%. Progression-free survival rate was 75.0% (9/12) at 6 months and 50.0% (6/12) at 1 year. The one-year overall survival rate was 75.0%. There were no severe temozolomide-related toxicities. CONCLUSIONS: Concurrent temozolomide with three-dimensional conformal radiotherapy and followed by 6 cycles of temozolomide chemotherapy for diffuse brainstem gliomas have a better clinical efficacy, good tolerance and with no severe toxicities.

[Detecting and identifying 3 novel single nucleotide polymorphisms in DNA sequence of epidermal growth factor precursor from Buyi and Han individuals].

OBJECTIVE: To examine the single nucleotide polymorphism (SNP) distributed in exon 20, 21 and intron 20 of epidermal growth factor precursor gene (preproEGF) of Buyi and Han individuals. METHODS: Eleven primer sets were designed and synthesized for PCR, that genomic DNA of Buyi or Han individual was used as the template, to amplify and sequence respectively the large fragment DNA from preproEGF gene. BLAST programs were applied to compare and identify the SNPs from the sequenced PCR products or amplified DNA fragments. RESULTS: 4.5 kb DNA fragments long over 20th, 21st exon and 20th intron structures of preproEGF gene were got by PCR respectively from genomic DNAs of Buyi and Han individuals. Results of DNA sequencing showed two SNPs in 4. 5 kb fragment of Han individual, of which one was sited at C86380T of preproEGF gene and another positioned at 84580 bp (T/-), while one SNP was observed in Buyi individual, which was located at T84329C of preproEGF gene. GenBank dbSNP database showed that C86380T SNP in 20th intron of preproEGF gene has not been reported yet from Han group and other cohorts except it has been reported from European and Sub-Saharan groups; and also that T84329C SNP has not been reported yet from Buyi group although it has been reported from Han group. CONCLUSIONS: Our study demonstrates that the Han individual is with C86380T SNP located in 20th intron of human preproEGF gene; and that the Buyi individual has the T84329C SNP sited in 20th intron of human preproEGF gene. However, another Han SNP (T/-) positioned at 84580 bp need to be further confirmed.

Biochemical pathways in the antiatherosclerotic effect of berberine.

BACKGROUND: This study investigated the inhibitory effect of berberine (BBR) on lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression via the mitogen activated protein kinase (MAPK) signalling cascade pathways in human peripheral blood monocytes (PBMC). METHODS: PBMC from whole blood were isolated and cultured for up to 24 hours after division into 5 groups treated with LPS, LPS + BBR 25 micromol/L, LPS + BBR 50 micromol/L or LPS + BBR 100 micromol/L and untreated. Monocytes were extracted for RT-PCR and Western blot analyses to examine COX-2 mRNA and protein activated expression of p38 mitogen activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK) and extracellular regulated kinases 1/2 (ERK1/2) signalling pathways. RESULTS: COX-2 mRNA and protein expression decreased to a minimum at 12 hours after BBR treatment (P < 0.05). With the increasing concentration of BBR treatment, the COX-2 expression decreased progressively (P < 0.01). With BBR treatment for 6, 12 or 24 hours at three doses, ERK1/2 protein expression was significantly inhibited. For the JNK pathway, only with the treatment of BBR at the concentration of 100 micromol/L was JNK protein expression inhibited compared with the LPS stimulation group (P < 0.01). Irrespective of the BBR concentration, no difference was shown between the BBR group and the LPS group for p38MAPK protein expression. Human monocytes COX-2 mRNA, by RT-PCR, and protein expression, by Western blot analysis, were inhibited when incubated with PD98059, SP600125 and SB203580 (P < 0.05). CONCLUSIONS: Berberine inhibits COX-2 expression via the ERK1/2 signalling pathway and, possibly, at a high dosage via the JNK pathway. P38MAPK may have no relationship with the effect of BBR in PBMC. Berberine inhibited COX-2 mRNA and protein expression in a dose dependent manner and suppressed COX-2 expression to a minimal level after 12 hours of berberine treatment.

Effects of aspirin on atherosclerosis and the cyclooxygenase-2 expression in atherosclerotic rabbits.

BACKGROUND: Atherosclerosis is a complex vascular inflammatory disease. Aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. In this study, the effectiveness of aspirin in suppressing atherosclerosis and the inflammation process was evaluated in rabbits fed with a high fat diet. METHODS: Eighteen male New Zealand rabbits were randomly divided into 3 groups: control group, untreated cholesterol-fed group, aspirin treated cholesterol-fed group, which were fed for 12 weeks. After 12 weeks, the aorta was harvested for pathologic morphology observation. Immunohistochemical analysis of cyclooxygenase-2 (COX-2), macrophage and vascular smooth muscle cell (VSMC) was performed. The statistical analysis was performed by the statistical program SPSS10.0. RESULTS: The aorta plaque/intima size (P/I) by pathologic morphology observation was 0%, (59.6 +/- 13.7)% and (36.3 +/- 16.5)% in the control, untreated cholesterol-fed group and aspirin treated group, respectively. The maximum plaque thickness, the degree of artery stenosis and the proportion of the intimal circumference occupied by atheroma of the 3 groups were significantly different from each other (P < 0.01). The expression of COX-2 and macrophage in plaque of the aspirin treated group were decreased compared with that in untreated cholesterol-fed group. However, no difference was found in the expression of VSMC between the aspirin treated and the untreated cholesterol-fed group. CONCLUSION: The mechanism of atherosclerosis suppression by aspirin in cholesterol-fed rabbits is related to the inhibition of COX-2 expression together with the reduced inflammation followed by, but not related to the hypolipidemic effects.

[The effect of breast cancer specific gene 1 in the prognosis of breast cancer].

OBJECTIVE: To detect breast cancer specific gene 1 (BCSG1) expression in different breast tissue, analysis its correlation with clinical parameters and evaluate the prognosis of breast cancer. METHODS: The expression of BCSG1 was detected by reverse transcription-polymerase chain reaction (RT-PCR) in surgical specimens from 84 cases of breast disease patients selected randomly at XinHua Hospital affiliated with Shanghai Second Medical University from September 1999 to December 2002. Of 84 cases, 72 case were breast cancer. Statistic analysis BCSG1 gene expression correlation with clinical parameters of breast cancer. 72 breast cancers were followed up (4 - 43 months) to set up independent prognosis factor by survival analysis. RESULTS: BCSG1 was undetectable in all benign breast lesions, while was detectable in 36.1% of all breast cancer samples (26/72), in which 79.2% of stage III/IV cases were positive (19/24). The expression of BCSG1 was tightly correlated with the stage (P = 0.000) and the size of tumor (P = 0.007). Both ER (P = 0.027) and BCSG1 (P = 0.001) were the independent prognosis factor of breast cancer. CONCLUSION: BCSG1 is one of independent tumor marker of breast cancer, the expression of BCSG1 is closely correlated to the stage of breast cancer and the tumor size. Maybe, BCSG1 is a new prognosis factor of breast cancer.

Therapeutic effect of carotid artery stenting versus endarterectomy for patients with high-risk carotid stenosis.

OBJECTIVE: To investigate therapeutic effect of carotid artery stenting versus endarterectomy for patients with high-risk carotid stenosis. METHODS: A total of 130 carotid stenosis patients at high-risk of stroke were randomly divided into stenting group and endarterectomy group, including 65 patients in each group. The patients in the endarterectomy group underwent endarterectomy and those in the stenting group received carotid artery stenting for treatment. RESULTS: After operation, carotid intima-media thickness (IMT), plague areas and carotid artery resistance indexes in both groups decreased significantly, and the carotid artery peak blood flow velocities increased significantly and had significant differences with that before operation (P < 0.05). After operation, total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) values in two groups all significantly decreased, and intragroup and intergroup differences were statistically significant (P < 0.05). Postoperative three months of followed-up found that the mortality rate in stenting group was 1.5% and that in the endarterectomy group was 9.2%; the mortality rate in the stenting group was significantly lower than the endarterectomy group (P < 0.05). CONCLUSION: Compared with carotid endarterectomy, application of carotid artery stenting can effectively promote patency of blood flow in the carotid artery, and exertion of its effect is related to lowering lipid and lowering inflammatory factor expression.

11C-CHO PET in optimization of target volume delineation and treatment regimens in postoperative radiotherapy for brain gliomas.

OBJECTIVE: We explored the clinical values of (11)C-choline ((11)C-CHO) PET in optimization of target volume delineation and treatment regimens in postoperative radiotherapy for brain gliomas. METHODS: Sixteen patients with the pathological confirmation of the diagnosis of gliomas prior to receiving radiotherapy (postoperative) were included, and on whom both MRI and CHO PET scans were performed at the same position for comparison of residual tumors with the two techniques. (11)C-CHO was used as the tracer in the PET scan. A plain T1-weighted, T2-weighted and contrast-enhanced T1-weighted imaging scans were performed in the MRI scan sequence. The gliomas' residual tumor volume was defined as the area with CHO-PET high-affinity uptake and metabolism (V(CHO)) and one with MRI T1-weighted imaging high signal intensity (V(Gd)), and was determined by a group of experienced professionals and clinicians. RESULTS: (1) In CHO-PET images, the tumor target volume, i.e., the highly metabolic area with a high concentration of isotopes (SUV 1.016-4.21) and the corresponding contralateral normal brain tissues (SUV0.1-0.62), was well contrasted, and the boundary between lesions and surrounding normal brain tissues was better defined compared with MRI and (18)F-FDG PET images. (2) For patients with brain gliomas of WHO Grade II, the SUV was 1.016-2.5; for those with WHO Grades III and IV, SUVs were >26-4.2. (3) Both CHO PET and MRI were positive for 10 patients and negative for 2 patients. The residual tumor consistency between these two studies was 75%. Four of the 10 CHO-PET-positive patients were negative on MRI scans. The maximum distance between V(Gd) and V(CHO) margins was 1.8 cm. (4) The gross tumor volumes (GTVs) and the ensuing treatment regimens were changed for 31.3% (5/16) of patients based on the CHO-PET high-affinity uptake and metabolism, in which the change rate was 80% (4/5), 14.3 % (1/7) and 0% (0/4) for patients with WHO Grade II III, and IV gliomas, respectively. CONCLUSION: Our data demonstrate that difference exists between CHO PET and MRI by which to judge and identify residual tumor for patients with brain gliomas. CHO PET is considered to be a supplementary diagnostic approach for MRI. Biological tumor target volume (BTV) displayed in the CHO PET images is useful in determining or delineating the radiotherapy target volume and making decisions in selecting treatment regimens. Tumor target volume may be defined more accurately and rationally when the CHO PET is combined with MRI.

[Sparing normal oral tissues with individual dental stent in radiotherapy for primary nasopharyngeal carcinoma patients].

BACKGROUND & OBJECTIVE: With the progression of radiotherapy techniques, the 5-year overall survival rate of nasopharyngeal carcinoma (NPC) patients has increased obviously. As the survival time prolonged, more and more attention was paid to various radiation sequelae and the quality of life of the patients. This study was to explore the role of individual dental stent in sparing normal oral tissues for primary NPC patients in radiotherapy by pushing the tongue and a part of oral mucous membrane away from the radiation fields. METHODS: Irradiation dose and volume of the tongue of a NPC patient before and after wearing dental stent was evaluated. A total of 43 patients were randomized into 2 groups: 19 in trial group and 24 in control group. Trial group wore dental stent during radiotherapy, while control group did not. Patients' weight, taste, oral mucous reaction, and tongue mucous reaction before radiotherapy and every week during radiotherapy were examined. RESULTS: Dosimetric analysis proved that the irradiation dose and volume of the tongue decreased obviously in trial group. The occurrence rate of grade 1-2 mucositis of the oral cavity was higher in trial group than in control group (73.68% vs. 62.50%), but the occurrence rate of grade 3-4 mucositis was lower in trial group than in control group (26.32% vs. 37.50%, P=0.470). By the completion of radiotherapy, 4 (21.05%) patients in trial group and 19 (79.17%) in control group suffered from taste dysfunction (P<0.001). CONCLUSION: Individual dental stent is useful in sparing the oral mucous membrane and preserving taste for primary NPC patients in radiotherapy.

[Dosimetric analysis of radiotherapy with middle shielding blocks of different widths at the lower cervical supraclavicular field for stage N2-3 nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Anterior tangential field irradiation with middle shielding block at the lower cervical and supraclavicular region is needed in the conventional radiotherapy for stage N2-3 nasopharyngeal carcinoma (NPC), but there are still some disagreements on block width. This study was to explore a reasonable block width by dosimetric analysis of anterior tangential field irradiation with middle shielding blocks of different widths designed by the 3-dimensional treatment planning system (3D-TPS) at the lower cervical supraclavicular region for stage N2-3 NPC. METHODS: Ten untreated patients with stage N2-3 NPC received 3D-TPS-designed irradiation plan. For every patient, a gradual shrinking field technique was adopted. Single anterior tangential fields were set at the lower cervical and supraclavicular region and irradiated with middle shielding blocks of different widths: 0 cm (Plan A), 2.1 cm (Plan B), 2.5 cm (Plan C), and 3 cm (Plan D) for the first 40 Gy, then 3 cm for residual dose for all 4 plans. The prescribed doses were the same for 4 plans for every patient. The irradiated volumes and doses of target volumes and organs at risk among the 4 plans were compared. RESULTS: The high dose coverage (V95 and V90) of plan target volume (PTV) for the subclinical lesion region at the lower cervical supraclavicular region (PTV50a) was significantly higher in Plan A than in Plans B, C, and D (82.44% vs. 78.21%, 77.10% and 73.80% for V95, 87.89% vs. 84.03%, 82.68% and 77.50% for V90, P<0.05), and significantly higher in Plans B and C than in Plan D (P<0.05), but there was no difference between Plans B and C (P>0.05). There was no significant difference in high dose coverage (V95 and V90) of PTV for the primary gross tumor region (PTVnx), PTV for the cervical metastatic nodes (PTVnd), PTV for the high risk region around primary gross tumor (PTVnx60), PTV for the high risk region around metastatic nodes (PTVnd60), and subclinical lesion region above cricoid cartilage (PTV50b) among the 4 plans. There was no difference in the doses for the spinal cord and larynx among the 4 plans. The maximal doses for 50% volumes of target organs (D50) were significantly higher in Plan A than in Plans B, C, and D (49.47 Gy vs. 41.95 Gy, 38.73 Gy, and 26.82 Gy for the thyroid gland, 44.52 Gy vs. 8.41 Gy, 7.03 Gy, and 5.63 Gy for the esophagus, 44.18 Gy vs. 10.16 Gy, 8.55 Gy, and 7.60 Gy for the trachea, P<0.05), and higher in Plans B and C than in Plan D (P<0.05), but there was no difference between Plans B and C (P>0.05). The normal tissue complication probability (NTCP) of the thyroid gland was significantly higher in Plan A than in Plans B, C, and D (7.9% vs. 4.8%, 4.3%, and 3.0%, P<0.05), and higher in Plans B and C than in Plan D, but there was no difference between Plans B and C (P>0.05). There were no difference in the doses for the spinal cord and larynx among the 4 plans. The maximal doses for 50% volumes of target organs (D50) were significantly higher in Plan A than in Plans B, C, and D (49.47 Gy vs. 41.95 Gy, 38.73 Gy, and 26.82 Gy for the thyroid gland, 44.52 Gy vs. 8.41 Gy, 7.03 Gy, and 5.63 Gy for the esophagus, 44.18 Gy vs. 10.16 Gy, 8.55 Gy, and 7.60 Gy for the trachea, P<0.05), and higher in Plans B and C than in Plan D (P<0.05), but there was no difference between Plans B and C (P>0.05). The normal tissue complication probability (NTCP) of the thyroid gland was significantly higher in Plan A than in Plans B, C, and D (7.9% vs. 4.8%, 4.3%, and 3.0%, P<0.05), and higher in Plans B and C than in Plan D, but there was no difference between Plans B and C (P>0.05). There were no difference in the NTCP of other organs at risk among the 4 plans (P>0.05). CONCLUSIONS: Not obviously increasing the irradiation doses for critical organs at risk, Plan A has the best high dose coverage at the subclinical lesion region of the lower cervical and supraclavicular region, while Plan D the worst. We recommend to use no middle shielding block in the anterior tangential field for the first 40 Gy, then use individual middle shielding blocks of 2.1-2.5 cm in the institutes at where set up error is small.

Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in patients with lymph node-negative breast carcinoma.

Twenty-five to thirty percent of patients with node-negative breast cancer are expected to relapse following surgery, therefore great efforts have been made to identify new prognostic markers that could be useful in defining patients for additional therapy. The expression of MMP-2 and MMP-9 has been associated with high potential of metastasis in several human carcinomas including breast cancer. In the present study we examined the prognostic value of immunoreactive MMP-2/MMP-9 protein in 270 consecutive lymph node negative cases who received radical mastectomy or modified radical mastectomy. Among the patients, 211 cases received adjuvant endocrine therapy and/or adjuvant chemotherapy. Using immunohistochemical assay, we found that 56.7% of the resected tumors were positive for MMP-2 whereas 59.6% of the samples were positive for MMP-9. Chi2 test demonstrated a significant direct association between MMP-2 and MMP-9 (p < 0.001); positive immunostaining of MMP-2 was significantly related to higher tumor grade (p < 0.001) and larger tumor size (p = 0.012); positive immunostaining of MMP-9 was significantly related to higher tumor grade (p = 0.002). In univariate analysis, using Cox-proportional hazard model we found MMP-2, MMP-9 and the co-expression of MMPs (MMP2/MMP9) were significantly associated with patients' relapse free survival (p = 0.016, 0.015 and 0.013 respectively) but not overall survival (p = 0.122, 0.320 and 0.091 respectively). Log-rank test also showed that MMP-2, MMP-9 or the co-expression of MMP2/MMP9 was unfavorable prognostic factor for relapse free survival but not overall survival. In subgroup analysis, we found MMPs were more prognostic for patients with no adjuvant treatment than for patients with adjuvant therapy. In multivariate analysis, using Cox-proportional hazard model we found co-expression of MMPs, larger tumor size and higher tumor grade were unfavorable for relapse free survival (p = 0.038, 0.007 and 0.015 for each). We concluded that MMP-2 and MMP-2 are unfavorable prognostic factors in breast cancer patients. They might be potential predictive factor for adjuvant systemic therapy. The co-expression of MMP-2 and MMP-9 has significantly prognostic value in node-negative patients.