Catalytic Asymmetric Synthesis of Vicinal Quaternary Stereocenters Enabled by Alkylation of α,α-Disubstituted Aldehydes with 3-Bromooxindoles.

An organocatalytic enantioselective alkylation of α,α-disubstituted aldehydes with 3-bromooxindoles is reported. Enantioenriched oxindoles with vicinal quaternary stereocenters are accessed by an asymmetric conjugate addition process of branched aldehydes with o-azaxylylene intermediates (indol-2-ones). Key to the success of highly diastereo- and enantioselective transformations is the combined use of a triphenylsilyl-protected ß-amino alcohol catalyst derived from the spiropyrrolidine scaffold and 3,5-dinitrobenzoic acid. This study also presents a rare example of aldehyde alkylation with the formation of consecutive quaternary stereocenters.

[Correlation analysis between body mass index and clinical characteristics of rheumatoid arthritis].

OBJECTIVE: To analyze the clinical features of overweight and obese rheumatoid arthritis (RA)patients, and the relationship between body mass index (BMI) and disease characteristics. METHODS: The demographic data, extra-articular manifestations, comorbidities, and disease activity of RA patients admitted to the Rheumatology and Immunology Department of Peking University Third Hospital from January 2015 to December 2020 were collected, and the above characteristics of overweight and obese RA patients were retrospectively analyzed. According to the WHO, BMI≥30 kg/m2 referred to obese individuals, 25≤BMI < 30 kg/m2 referred to overweight individuals, 18.5≤BMI < 25 kg/m2 referred to normal individuals, BMI < 18.5 kg/m2 referred to reduced body mass individuals. t test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non-normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, Chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. Analyzing whether overweight or obesity was associated with comorbidities using Logistic regression adjusted confounding factors. RESULTS: A total of 481 RA patients were included in this study, with an average BMI value of (23.28±3.75) kg/m2.Of the patients, 31 cases (6.5%) were with BMI < 18.5 kg/m2, 309 cases (64.2%) with 18.5≤ BMI < 25 kg/m2, amounting to 340 cases (70.7%). There were 119 overweight individuals (25≤ BMI < 30 kg/m2, 24.7%) and 22 obese individuals (BMI≥30 kg/m2, 4.6%), totaling 141 (29.3%).The proportion of the overweight and obese RA patients suffering from hypertension (57.4% vs. 39.1%, P < 0.001), diabetes (25.5% vs. 15.0%, P=0.006), hyperlipidemia (22.7% vs. 10.9%, P=0.001), fatty liver (28.4% vs. 7.4%, P < 0.001), osteoarthritis (39.0% vs. 29.4%, P=0.040) was significantly higher, and the proportion of the patients with osteoporosis(59.6% vs. 70.9%, P=0.016) and anemia (36.2% vs. 55.6%, P < 0.001) was significantly lower. However, there was no difference between the two groups in coronary heart disease (5.7% vs. 7.6%, P=0.442), cerebrovascular disease (6.4% vs. 8.8%, P=0.372) and peripheral atherosclerosis (9.2% vs. 7.6%, P=0.565).The median C-reactive protein (CRP, 1.52 mg/dL vs. 2.35 mg/dL, P=0.008), median erythrocyte sedimentation rate (ESR, 34.0 mm/h vs. 50.0 mm/h, P=0.003), pain visual simulation score (VAS) (3.66±3.08 vs. 4.40±2.85, P=0.011), and 28 joint disease activity scores (DAS-28, 5.05±1.60 vs. 5.45±1.52, P=0.010) in the overweight and obese RA group were all lower than those in the normal and reduced weight groups. Multivariate regression analysis showed that overweight and obesity was an independent risk factor for hypertension, diabetes, hyperlipidemia and fatty liver, and had protective effects on osteoporosis and anemia. CONCLUSION: In RA patients, RA disease activity is lower in overweight and obesity patients. Overweight and obesity is associated with hypertension, diabetes and hyperlipidemia, but not with cardiovascular and cerebrovascular diseases.

[Dose-response relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children]. / 幼儿园儿童年龄与肺炎链球菌疫苗覆盖率间的剂量-ååº”å ³ç³».

OBJECTIVES: To investigate the potential relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children, and to provide a basis for guiding vaccination and developing new protein vaccines. METHODS: The stratified cluster random sampling method was used to select 1 830 healthy children from six kindergartens in Shunde District, Foshan City, China, and nasopharyngeal swabs were collected for the isolation and identification of Streptococcus pneumoniae. The logistic regression model based on restricted cubic spline was used to analyze the dose-response relationship between age and Streptococcus pneumoniae vaccination coverage. RESULTS: The rate of nasal Streptococcus pneumoniae carriage was 22.46% (411/1 830) among the kindergarten children, with the predominant serotypes of 6B, 19F, 15A, 23A, 34, and 23F. The coverage rates of 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were 53.0% and 57.9%, respectively, and there was a significant non-linear dose-response relationship between age and the coverage rates of PCV10 and PCV13 (P<0.05), with a higher coverage rate of PCV10 (88.0%) and PCV13 (91.1%) in the children aged 2 years. There was a significant non-linear dose-response relationship between age and the coverage rates of pilus islet 1 (PI-1) and pilus islet 2 (PI-2) (P<0.05), with a lower vaccination coverage rate for PI-1 (37.7%) and PI-2 (16.1%). The coverage rates of PI-1 (13.0%-58.5%) and PI-2 (6.0%-29.4%) were lower in all age groups. The virulence genes lytA (99.5%) and ply (99.0%) associated with candidate protein vaccines showed higher vaccination coverage rates. CONCLUSIONS: There is a significant non-linear dose-response relationship between the age of kindergarten children and the coverage rates of PCV10 and PCV13 serotypes, and kindergarten children aged 2 years have a relatively high coverage rate of PCV. The high prevalence of the virulence genes lytA and ply shows that they are expected to become candidate virulence factors for the development of a new generation of recombinant protein vaccines.

Co-carriage of Streptococcus pneumoniae and Moraxella catarrhalis among preschool children and its influencing factors. / å­¦é¾„å‰å„¿ç«¥è‚ºç‚Žé“¾çƒèŒå’Œå¡ä»–èŽ«æ‹‰èŒæºå¸¦çŠ¶æ€åŠå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the carriage status of Streptococcus pneumoniae (S.pneumoniae) and Moraxella catarrhalis (M. catarrhalis) in preschool children and the influencing factors for the carriage status. METHODS: The stratified cluster sampling method was used to select 2 031 healthy children from seven kindergartens in Shunde District of Foshan in Guangdong, China. Nasal swabs were collected from all children for the isolation and identification of S. pneumoniae and M. catarrhalis. The carriage status of S. pneumoniae and M. catarrhalis was analyzed in terms of its association with demographic features and hospital- and community-related factors. RESULTS: The carriage rates of S. pneumoniae and M. catarrhalis were 21.81% and 52.44%, respectively among the children. The co-carriage rate of S. pneumoniae and M. catarrhalis was 14.87%. The correspondence analysis showed that the factors such as lower grade, non-local registered residence, living in rural areas, small living area, history of respiratory tract infection but no history of antibiotic use, allergic skin diseases, and no hospital-related exposure history were significantly associated with the co-carriage of S. pneumoniae and M. catarrhalis among the children (P<0.05). CONCLUSIONS: Co-carriage of S. pneumoniae and M. catarrhalis can be observed in preschool children. Young age, poor living environment, a history of respiratory tract infection but no history of antibiotic use, allergic skin diseases, and no hospital-related exposure history are important risk factors for the co-carriage of S. pneumoniae and M. catarrhalis in preschool children.

Characterization of complete mitochondrial genome of the common tiger, Danaus genutia (Lepidoptera: Nymphalidae: Danainae) and phylogenetic implications within the subfamily Danainae.

Nymphalidae is the most diverse butterfly family worldwide, with more than 6000 species, whereas the mitogenomic data of nymphalid species, especially the subfamily Danainae, is still lacking for more comprehensive systematic studies. To this contribution, the complete mitogenome of Danaus genutia (Lepidoptera: Nymphalidae: Danainae) was determined via sequencing and annotating. The mitogenome in total consists of 15,255 base pairs (bp), containing 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and a 440-bp noncoding A+T-rich region. Furthermore, phylogeny of the subfamily Danainae was reconstructed applying maximum likelihood and Bayesian inference on the basis of the mitogenomic data sets. Combined with our analysis and previous studies, the genus-level phylogenetic relationships within the subfamily Danainae are ((Tirumala + Danaus) + ((Idea + Euploea) + (Ideopsis + Parantica))). This study offers molecular information and provides a new perspective for phylogenetic research within the subfamily Danainae.

SARS-CoV-2 turned positive in a discharged patient with COVID-19 arouses concern regarding the present standards for discharge.

An outbreak of coronavirus disease (COVID-19) in Wuhan, China caused by SARS-CoV-2 has led to a serious epidemic in China and other countries, resulting in worldwide concern. With active efforts of prevention and control, more and more patients are being discharged. However, how to manage these patients normatively is still challenging. This paper reports an asymptomatic discharged patient with COVID-19 who retested positive for SARS-CoV-2, which arouses concern regarding the present discharge standards of COVID-19.

Pancreatic neuroendocrine tumor: prediction of the tumor grade using magnetic resonance imaging findings and texture analysis with 3-T magnetic resonance.

PURPOSE: The purpose of this study was to evaluate the performance of magnetic resonance imaging (MRI) findings and texture parameters for prediction of the histopathologic grade of pancreatic neuroendocrine tumors (PNETs) with 3-T magnetic resonance. PATIENTS AND METHODS: PNETs are classified into Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors based on the Ki-67 proliferation index and the mitotic activity. A total of 77 patients with pathologically confirmed PNETs met the inclusion criteria. Texture analysis (TA) was applied to T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) maps. Patient demographics, MRI findings, and texture parameters were compared among three different histopathologic subtypes by using Fisher's exact tests or Kruskal-Wallis test. Then, logistic regression analysis was adopted to predict tumor grades. ROC curves and AUCs were calculated to assess the diagnostic performance of MRI findings and texture parameters in prediction of tumor grades. RESULTS: There were 31 G1, 29 G2, and 17 G3 patients. Compared with G1, G2/G3 tumors showed higher frequencies of an ill-defined margin, a predominantly solid tumor type, local invasion or metastases, hypo-enhancement at the arterial phase, and restriction diffusion. Four T2-based (inverse difference moment, energy, correlation, and differenceEntropy) and five DWI-based (correlation, contrast, inverse difference moment, maxintensity, and entropy) TA parameters exhibited statistical significance among PNETs (P<0.001). The AUCs of six predicting models on T2WI and DWI ranged from 0.703-0.989. CONCLUSION: Our data indicate that MRI findings, including tumor margin, texture, local invasion or metastases, tumor enhancement, and diffusion restriction, as well as texture parameters can aid the prediction of PNETs grading.

[Diffusion weighted imaging combined with dynamic contrast enhanced magnetic resonance imaging in monitoring therapeutic efficacy for hepatocellular carcinoma after transcatheter arterial chemoembolization].

OBJECTIVE: To evaluate the diagnostic value of diffusion weighted imaging (DWI) combined with dynamic contrast-enhanced (DCE) MRI in monitoring the efficacy for hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). METHODS: MRI and CT scan were performed 4-6 weeks after TACE in 31 patients.With digital signature algorithm (DSA) examination as the reference standard, the value in detection of the residue and recurrence of HCC was compared between MRI and CT results. RESULTS: Seventy-three lesions were detected in 31 patients. Fourteen lesions confirmed by DSA had no tumor staining, and 59 lesions had tumor staining. Diagnostic sensitivity and specificity of DCE-CT were 78.0% and 85.7%, respectively; while those of DWI combined with DCE-MRI were 100% and 92.9% (P<0.001). CONCLUSION: DWI combined with DCE-MRI is more effective than DCE-CT in detecting the residue and recurrence of HCC after TACE.

[Effects of baicalin on apoptosis in rats with autoimmune encephalomyelitis].

OBJECTIVE: To study the therapeutic efficacy of baicalin and its effect on apoptosis of inflammatory cells in spinal cords in Wistar rats with autoimmune encephalomyelitis (EAE). METHODS: Forty-four rats were randomly divided into four groups: normal control group (control, n=10), EAE group (n=12), and two intervention groups with dexamethasone (DXM) or baicalin. Seven days after immunization, the two intervention groups were injected intraperitoneally with DXM (1 mg/kg) and baicalin (200 mg/kg) for 1 week, respectively. The spinal cords were removed 14 days after immunization, and stained with hematoxylin and eosin. MBP expression in spinal cords was detected by immunohistochemistry. The apoptosis of inflammatory cells in spinal cords was detected by TUNEL. RESULTS: The weight gain rate in the untreated EAE and the DXM or baicalin intervention groups were significantly lower than that in the control group (P<0.05). The weight gain rate in the baicalin intervention group was significantly higher than that in the untreated EAE and the DXM intervention groups (P<0.05). The scores of neurological function in the two intervention groups were significantly higher than that in the untreated EAE group (P<0.05). DXM or baicalin treatment significantly increased the MBP expression compared with the untreated EAE group (P<0.05). The apoptosis of inflammatory cells increased more in the DXM and the baicalin intervention groups compared with the untreated EAE groups (P<0.05). CONCLUSIONS: Baicalin has protective effects against EAE in rats. It can promote the apoptosis of inflammatory cells in spinal cords.

[Magnetic resonance signal detection of superparamagnetic iron oxide nanoparticles and its biological effects on endothelial cells].

OBJECTIVE: To investigate the magnetic resonance (MR) signal changes of superparamagnetic iron oxide (SPIO) and its biological effects on endothelial cells. METHODS: The citric-acid coated SPIO was synthesized by co-precipitation method. The human umbilical vein endothelial cells (HUVECs) were incubated with SPIO for 24 h in culture medium at iron concentration of 0.01, 0.05, 0.10, 0.15 mg/ml (experimental groups), and the cells incubated without SPIO served as control groups. The uptake efficiency of intracellular iron was measured by Prussian blue staining, and the cell viability was monitored by Calcein-AM method. The cell cytoskeleton (F-actin and tubulin), adherence and migration capacity were measured by immunofluorescence staining. The iron oxide nanoparticles distribution and the cellular organelle change were monitored by transmission electron microscopy (TEM). Quantification of particle uptake was measured by atomic absorption spectrometry. The MR signal of endothelial cells after labeling was monitored by Philips 3.0 T MR scanner. RESULTS: SPIO was uptaken by HUVECs in a concentration-dependence manner. Compared with the control group, cell viability was decreased along with the increase of iron concentration. Compared with the control group, the cell cytoskeleton was markedly disorganized and the FAK spot was bigger and sparser.The nanoparticles were mainly existed in lysosomes, and the higher concentration of SPIO, the more lysosomes and vacuoles presented in the cells. The iron content per cell was (55.86 +/-9.935) pg when the SPIO concentration was 0.15 mg/ml. The MR image showed that the cells labeled with SPIO resulted in the decrease of MR signal. CONCLUSION: The cells labeled with SPIO can be detected by MR. The cell viability, cytoskeleton, adherence and migration capacity of HUVECs are affected by citric-acid coated SPIO in a concentration-dependent manner.

[Magnetic resonance signal features of superparamagnetic iron oxide with different particle size and concentration].

OBJECTIVE: To investigate the magnetic resonance (MR) signal features of superparamagnetic iron oxide (SPIO) with different particle size and concentration. METHODS: The superparamagnetic iron oxide with different concentration and particle size was scanned by magnetic resonance; T1, T2 and T2(*) values of each group were recorded to evaluate the features of MR signals. RESULTS: The T1 value of SPIO with different particle size had negative linear relationship with concentration. In low concentration the T2 and T2(*) values were elevated markedly with the particle size decreased; while in high concentration the T2 and T2(*)values were elevated gently with particle size decreased. lg(T2), particle size and concentration of SPIO had linear relationship. CONCLUSIONS: SPIO affects magnetic resonance signal mainly with effect on T1 and T2. T2 value can be regarded as the major detection index in the magnetic resonance scan of SPIO. There is a linear relationship among particle size, SPIO concentration and lg(T2) value.

[Expression of odorant receptor genes on the olfactory epithelium following olfactory nerve disconnection].

OBJECTIVE: To constitute the animal model of unilateral olfactory nerve transection and observe the expression level and distribution of odorant receptors. METHODS: Thirty-two rats were divided into two groups: the olfactory nerve transection group (20) and the control group (12). The former group received the operation to transect the left olfactory nerve following the left olfactory bulb was exposed under microscope and the latter group did not give any disposal. At every stage of five days, two weeks, four weeks and six weeks after the operation, five rats from the nerve transection group and three from the control group were anaesthetized simultaneously, and olfactory epithelium were taken out after transcardial perfusion, then paraffin imbedding. Coronal sections were sliced for HE staining to observe the thickness changes of the olfactory epithelium, and for in situ hybridization (ISHs) to investigate the expression of olfactory receptor genes (Olr287, Olr226, Olr1493 and Olr1654) in the epithelium, also to evaluate the changes of the expression level and location of the selected receptors during the regeneration of olfactory epithelium. RESULTS: HE staining showed that 5 days after the operation cell quantity and thickness of the olfactory epithelium decreased obviously, which increased gradually 2 or 4 weeks after operation. After 6 weeks' recovery, the thickness of the epithelium could reach the control level. The pattern of cell staining by ISH showed a specific spatial distribution along the anteroposterior (AP) and dorsoventral (DV) axis. Evidence suggested that odorant receptors were distributed in continuous and multiple overlapping bands in the normal or nerve transected-recovered epithelium rather than in the conventionally accepted three or four zones. The data also demonstrated that the distribution of sensory neuron types, as identified and defined by odorant receptor expression, was restored to normal or nearly so by 6 weeks after operation. Likewise, the numbers of probe-labeled neurons in the nerve transected-recovered had an obvious decrease 5 days after olfactory nerve transection. Reactive cells (x(-) +/- s) of Olr1493 in the operated side was (53.9 +/- 19.9), compared with (419.0 +/- 21.2) in the unoperated side, there was statistic significance between them (t = 63.960, P < 0.01). Reactive cells increased gradually according to the regeneration of the epithelium, and were nearly equivalent to the normal side 6 weeks later without significant differentiation (t = 2.600, P > 0.05), according to the absolute positive cells in the operated and unoperated side of (417.8 +/- 32.4) and (445.3 +/- 10.0) respectively. CONCLUSION: The regeneration of the sensory neurons and receptors, both the number and the distribution, can recover to normal after olfactory nerve transection.

[Experimental study of hippocampal neuronic lesion in ischemic rat by magnetic resonance spectroscopy].

AIM: To evaluate N-acetylaspartate reflecting the neuronal lesion in middle cerebral artery occlusion and reperfusion rat by magnetic resonance spectroscopy (MRS). METHODS: Sixteen adult Wistar rats with MCAO reperfusion and ten pseudooperation rats were performed MRS in vivo at the sixth weeks, then pathologic examination of HE staining and immunohistochemical staining were made. We compared hippocampus modality, cell density and immunohistochemical results with N-acetylaspartate, creatine changes and ration of NAA/Cr. RESULTS: The values of NAA, Cr and NAA/Cr of ipsilateral hippocampus lesion in MCAO reperfusion rats (2.05 +/- 0.33, 2.42 +/- 0.41 and 0.86 +/- 0.10) were visiblly decreased than contralateral hippocampus (3.45 +/- 0.58, 3.10 +/- 0.93, 1.18 +/- 0.32) and control group (3.42 +/- 0.43, 3.57 +/- 0.47, 0.98 +/- 0.14). But the level of decreased NAA is not corresponding to the degree of neuronal death in ipsilateral region of hippocampus in histochemistry. CONCLUSION: MRS has perfect explanation of cell metabolic changes in CA1 region. Decrease of NAA represented neuron delayed injury. But the decreased level of NAA is not perfectly corresponded to the degree of neuron lost. This change has closed correlation with reactive astrocytes proliferation.

[Observation on therapeutic effect of herbs-partitioned moxibustion on Parkinson disease of 54 cases].

OBJECTIVE: To observe clinical therapeutic effect of herbs-partitioned moxibustion at Shenque (CV 8) on Parkinson disease. METHODS: Ninety cases of Parkinson disease were randomly divided into a treatment group (n=4) and a control group (n=36) in order of visiting. The two groups were treated with routine western medicine for treatment of Parkinson disease, and herbs-partitioned moxibustion at Shenque (CV 8) was added to the treatment group. Their comprehensive therapeutic effects were observed and modified UPDRS cumulative scores were compared. RESULTS: The total effective rate was 83.3% in the treatment group, significantly better than 58.3% in the control group (P < 0.01); the modified UPDRS cumulative score was reduced by 74.1% in the treatment group, significantly better than 16.7% in the control group (P < 0.01). CONCLUSION: Herbs-partitioned moxibustion at Shenque (CV 8) has a certain therapeutic effect on Parkinson disease.

[Preliminary study on Professor SUN Liu-he's academic thought].

Professor SUN Liu-he has been engaged in scientific research, clinical and teaching works for tens years and he is a meticulous scholar with great learning, rich clinical experience and great theoretical attainments. In clinical practice of many years, he summarizes and develops Kangai Plaster, Kangai Fushui Plaster, Ai tong Ling Plaster, and so on for acupoint sticking to treat tumors, and establishes Nu-needle hot-reinforcing method and Ti-Yun reducing method, enriching contents of needling methods, and he is good at application of specific points, established points and channel acupoints to treat refractory diseases with good results.