Gestational valproic acid exposure enhances facial stimulation-evoked cerebellar mossy fiber-granule cell transmission via GluN2A subunit-containing NMDA receptor in offspring mice.

Valproic acid (VPA) is one of the most effective antiepileptic drugs, and exposing animals to VPA during gestation has been used as a model for autism spectrum disorder (ASD). Numerous studies have shown that impaired synaptic transmission in the cerebellar cortical circuits is one of the reasons for the social deficits and repetitive behavior seen in ASD. In this study, we investigated the effect of VPA exposure during pregnancy on tactile stimulation-evoked cerebellar mossy fiber-granule cell (MF-GC) synaptic transmission in mice anesthetized with urethane. Three-chamber testing showed that mice exposed to VPA mice exhibited a significant reduction in social interaction compared with the control group. In vivo electrophysiological recordings revealed that a pair of air-puff stimulation on ipsilateral whisker pad evoked MF-GC synaptic transmission, N1, and N2. The evoked MF-GC synaptic responses in VPA-exposed mice exhibited a significant increase in the area under the curve (AUC) of N1 and the amplitude and AUC of N2 compared with untreated mice. Cerebellar surface application of the selective N-methyl-D-aspartate (NMDA) receptor blocker D-APV significantly inhibited facial stimulation-evoked MF-GC synaptic transmission. In the presence of D-APV, there were no significant differences between the AUC of N1 and the amplitude and AUC of N2 in the VPA-exposed mice and those of the untreated mice. Notably, blockade of the GluN2A subunit-containing, but not the GluN2B subunit-containing, NMDA receptor, significantly inhibited MF-GC synaptic transmission and decreased the AUC of N1 and the amplitude and AUC of N2 in VPA-exposed mice to levels similar to those seen in untreated mice. In addition, the GluN2A subunit-containing NMDA receptor was expressed at higher levels in the GC layer of VPA-treated mice than in control mice. These results indicate that gestational VPA exposure in mice produces ASD-like behaviors, accompanied by increased cerebellar MF-GC synaptic transmission and an increase in GluN2A subunit-containing NMDA receptor expression in the offspring.

Etomidate enhances cerebellar CF-PC synaptic plasticity through CB1 receptor/PKA cascade in vitro in mice.

Etomidate (ET) is a widely used intravenous imidazole general anesthetic, which depresses the cerebellar neuronal activity by modulating various receptors activity and synaptic transmission. In this study, we investigated the effects of ET on the cerebellar climbing fiber-Purkinje cells (CF-PC) plasticity in vitro in mice using whole-cell recording technique and pharmacological methods. Our results demonstrated that CF tetanic stimulation produced a mGluR1-dependent long-term depression (LTD) of CF-PC excitatory postsynaptic currents (EPSCs), which was enhanced by bath application of ET (10 µM). Blockade of mGluR1 receptor with JNJ16259685, ET triggered the tetanic stimulation to induce a CF-PC LTD accompanied with an increase in paired-pulse ratio (PPR). The ET-triggered CF-PC LTD was abolished by extracellular administration of an N-methyl-(D)-aspartate (NMDA) receptor antagonist, D-APV, as well as by intracellular blockade of NMDA receptors activity with MK801. Furthermore, blocking cannabinoids 1 (CB1) receptor with AM251 or chelating intracellular Ca2+ with BAPTA, ET failed to trigger the CF-PC LTD. Moreover, the ET-triggered CF-PC LTD was abolished by inhibition of protein kinase A (PKA), but not by inhibition of protein kinase C inhibiter. The present results suggest that ET acts on postsynaptic NMDA receptor resulting in an enhancement of the cerebellar CF-PC LTD through CB1 receptor/PKA cascade in vitro in mice. These results provide new evidence and possible mechanism for ET anesthesia to affect motor learning and motor coordination by regulating cerebellar CF-PC LTD.

Clinical and functional analyses of the novel STAR c.558C>A in a patient with classic lipoid congenital adrenal hyperplasia.

Objective: Congenital lipid adrenal hyperplasia (LCAH) is the most serious type of congenital adrenal hyperplasia and is caused by steroid-based acute regulatory (STAR) protein mutations. Herein, we report compound heterozygous mutations c.558C>A (p.S186 R) and c.772C>T (p.Q258*) in a newborn 46 XY patient diagnosed with classic LCAH and explore their clinical and functional characteristics. Methods: Peripheral blood samples were collected from LCAH patient and their families. The pathogenic variant identified by whole-exome sequencing was further confirmed by Sanger sequencing and pedigree verification. The functional consequence and ability to convert cholesterol into progesterone of the identified STAR Q258* and S186 R mutations were analyzed by cell transfection and in vitro assays. Results: The proband was presented with severe glucocorticoid and mineralocorticoid deficiency, high adrenocorticotropic hormone, and enlarged adrenals. Heterozygous mutations p. S186 R and p. Q258* in the STAR gene were identified in the patient, and her parents were carriers, which is consistent with an autosomal recessive disorder. The STAR p. Q258* mutation has been reported and generates a truncated protein. The p. S186 R mutation is a novel variant that disrupts STAR. The residual STAR activities of p. S186R, p. Q258*, and p. S186R/p.Q258* were 13.9%, 7.3%, and 11.2%, respectively, of the wild-type, proving the main negative effects of the mutant proteins. Conclusion: Our findings reveal the molecular mechanisms underlying LCAH pathogenesis, further expanding the genotype and clinical spectrum of LCAH.

Opposing actions of CRF-R1 and CB1 receptor on facial stimulation-induced MLI-PC plasticity in mouse cerebellar cortex.

BACKGROUND: Corticotropin-releasing factor (CRF) is the major neuromodulator orchestrating the stress response, and is secreted by neurons in various regions of the brain. Cerebellar CRF is released by afferents from inferior olivary neurons and other brainstem nuclei in response to stressful challenges, and contributes to modulation of synaptic plasticity and motor learning behavior via its receptors. We recently found that CRF modulates facial stimulation-evoked molecular layer interneuron-Purkinje cell (MLI-PC) synaptic transmission via CRF type 1 receptor (CRF-R1) in vivo in mice, suggesting that CRF modulates sensory stimulation-evoked MLI-PC synaptic plasticity. However, the mechanism of how CRF modulates MLI-PC synaptic plasticity is unclear. We investigated the effect of CRF on facial stimulation-evoked MLI-PC long-term depression (LTD) in urethane-anesthetized mice by cell-attached recording technique and pharmacological methods. RESULTS: Facial stimulation at 1 Hz induced LTD of MLI-PC synaptic transmission under control conditions, but not in the presence of CRF (100 nM). The CRF-abolished MLI-PC LTD was restored by application of a selective CRF-R1 antagonist, BMS-763,534 (200 nM), but it was not restored by application of a selective CRF-R2 antagonist, antisauvagine-30 (200 nM). Blocking cannabinoid type 1 (CB1) receptor abolished the facial stimulation-induced MLI-PC LTD, and revealed a CRF-triggered MLI-PC long-term potentiation (LTP) via CRF-R1. Notably, either inhibition of protein kinase C (PKC) with chelerythrine (5 µM) or depletion of intracellular Ca2+ with cyclopiazonic acid (100 µM), completely prevented CRF-triggered MLI-PC LTP in mouse cerebellar cortex in vivo. CONCLUSIONS: The present results indicated that CRF blocked sensory stimulation-induced opioid-dependent MLI-PC LTD by triggering MLI-PC LTP through CRF-R1/PKC and intracellular Ca2+ signaling pathway in mouse cerebellar cortex. These results suggest that activation of CRF-R1 opposes opioid-mediated cerebellar MLI-PC plasticity in vivo in mice.

Cs2 CO3 -Promoted C-O Coupling Protocol Enables Solventless (Hetero)aryl Ether Synthesis under Air Atmosphere.

In this work, a Cs2 CO3 -promoted synthetic approach was identified for (hetero)aryl ether synthesis via the C-O coupling of various (hetero)aryl chlorides and alcohols/phenol. To our delight, the reactions could be carried out under transition-metal-free and solvent-free conditions. Moreover, analytical-grade reagents and air atmosphere were readily tolerated. To showcase the practical usefulness of the present protocol, the assembly of a bioactive molecule was facilely realized and the gram-scale production of selected ether products was also efficiently accomplished. In addition, density functional theory (DFT) studies, along with a few mechanistic experiments, were conducted to elucidate a proposed reaction pathway and rationalize the pivotal role of Cs2 CO3 in promoting this process. Hopefully, this work could provide useful information for researchers who are engaging in C-O cross-coupling reactions.

Metal-Free Synthesis of Heteroaryl Amines or Their Hydrochlorides via an External-Base-Free and Solvent-Free C-N Coupling Protocol.

Herein, a metal-free and solvent-free protocol was developed for the C-N coupling of heteroaryl halides and amines, which afforded numerous heteroaryl amines or their hydrochlorides without any external base. Further investigations elucidated that the basicity of amines and specific interactions derived from the X-ray crystallography analysis of 3j'·HCl played pivotal roles in the reactions. Moreover, this protocol was scalable to gram scales and applicable to drug molecules, which demonstrated its practical value for further applications.

A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice

The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced against emerging variants of concern (VOCs) 1,2. Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs 3,4. Attractive pharmacological targets to impede viral entry include type-II transmembrane serine proteases (TTSPs), such as TMPRSS2, whose essential role in the virus lifecycle is responsible for the cleavage and priming of the viral spike protein 5-7. Here, we identify and characterize a small-molecule compound, N-0385, as the most potent inhibitor of TMPRSS2 reported to date. N-0385 exhibited low nanomolar potency and a selectivity index of >106 at inhibiting SARS-CoV-2 infection in human lung cells and in donor-derived colonoids 8. Importantly, N-0385 acted as a broad-spectrum coronavirus inhibitor of two SARS-CoV-2 VOCs, B.1.1.7 and B.1.351. Strikingly, single daily intranasal administration of N-0385 early in infection significantly improved weight loss and clinical outcomes, and yielded 100% survival in the severe K18-human ACE2 transgenic mouse model of SARS-CoV-2 disease. This demonstrates that TTSP-mediated proteolytic maturation of spike is critical for SARS-CoV-2 infection in vivo and suggests that N-0385 provides a novel effective early treatment option against COVID-19 and emerging SARS-CoV-2 VOCs.

Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates

The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in less than 20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19. HighlightsO_LICHO-expressed S1-Fc protein is very immunogenic in various animals and can rapidly induce strong antibody production C_LIO_LIS1-Fc protein solicits strong neutralizing activities against live virus C_LIO_LIStable CHO cell line expressing 50 mg/L of S1-Fc and a 3,000 L Bioreactor can produce 3 million doses of human COVID-19 vaccine every 10 days, making it an accessible and affordable option for worldwide vaccination C_LI

Unraveling the sources and fluorescence compositions of dissolved and particulate organic matter (DOM and POM) in Lake Taihu, China.

Organic matter (OM), a complex entity with diverse functional groups and molecular sizes, has important effects on aquatic systems. We studied the optical compositions and sources of dissolved organic matter (DOM) and particulate organic matter (POM) in Lake Taihu, a large, shallow and eutrophic lake in China. Significant differences in optical compositions and sources occurred between the POM and DOM. The temporal-spatial distribution of the fluorescence indices suggested that the POM in Lake Taihu was mainly from autochthonous sources, but more exogenous characteristics were shown in POM in the river mouths compared with other regions. The chromophoric DOM in Lake Taihu mainly displayed autochthonous characteristics. The POM-DOM PARAFAC model was used to examine OM optical composition and five components were identified, which contained three protein-like components (C1, C2, and C5), a microbial humic-like component (C3), and a terrestrial humic-like component (C4). The POM was dominated by C5 in summer and autumn and C3 in winter and spring, and the DOM was dominated by protein-like components (C1, C2, and C5) through the entire year. The algae-dominated region had a relative higher contribution of tryptophan-like components of POM compared with the macrophyte-dominated region. A conceptual model based on the theory of "four phases of cyanobacteria bloom development" was proposed to fully describe the relationship between POM-DOM exchanges and cyanobacteria bloom development.

Correlation between osteopontin and caveolin-1 in the pathogenesis and progression of osteoarthritis.

Previous studies have produced contradictory results with regard to the role of osteopontin (OPN) and caveolin-1 in the pathology of osteoarthritis (OA). Thus, the aim of the present study was to investigate the correlation between OPN and caveolin-1 in the pathogenesis and progression of OA. Cartilage tissue samples were obtained from 50 individuals, of which 40 had been diagnosed with OA and 10 were normal healthy individuals. The samples were ascribed to four groups, namely the normal, minor, moderate and severe groups, on the basis of the improved Mankin grading system. Immunohistochemistry was applied to analyse the expression of OPN and caveolin-1. OPN and caveolin-1 were detected in the tissues of all four groups. The mutual comparisons of OPN expression levels among the groups revealed statistically significant differences (P<0.05). In addition, the mutual comparisons of caveolin-1 expression levels among the four groups demonstrated statistically significant differences (P<0.05), with the exception of that between the moderate and severe groups (P>0.05). Improved Mankin grading system scores were shown to correlate with the average grey level of OPN expression in each group (r=-0.824, P<0.01) and the average grey level of caveolin-1 expression (r=0.725, P<0.01). Furthermore, a statistically significant negative correlation was observed between the average grey levels of OPN and caveolin-1 expression (r=-0.676, P﹤0.05). Therefore, the results of the present study indicated that the correlation between OPN and caveolin-1 may play a significant role in the pathogenesis and progression of OA.

Green and sustainable City will become the development objective of China's Low Carbon City in future.

Environmental pollution and greenhouse gas emissions are becoming significant environmental issues in China, thus the sustainable development and revival of the country is impossible using the conventional path of encouraging economic growth at the expense of the environment. In response to the global warming, the prices of the traditional energy rise considerably, and a series of environmental problems, China must improve its own mode of economic development. Hundreds of Chinese cities have billions of square meters of buildings and most industry and the annual energy demand is an astronomical figure. China's government is facing increasing pressure in the low carbon international backdrop, and the low carbon city becomes the inevitable developmental direction of Chinese city in the foreseeable future. The description is first centered on energy structure/energy consumption per unit/urbanized status, and urban energy consumption status, and then concerned with the efforts and measures of Chinese government, to realize the energy saving. Finally, we present the developmental prospect and barriers and the promotion measures related to the low carbon city under the government policy, financial incentives and funding supports, etc.

The acute effect of mouth only breathing on time to completion, heart rate, rate of perceived exertion, blood lactate, and ventilatory measures during a high-intensity shuttle run sequence.

This study investigated the effect of restricting nasal breathing during a series of 20-m shuttle runs. Ten male participants (mean age = 21.7 ± 2.4 years, height = 1.80 ± 0.62 m, mass = 79.2 ± 10.4 kg, sum of 4 skinfolds = 54.5 ± 7.8 mm) were required to either (a) dive on the ground and complete a rolling sequence (condition = GRD) or (b) complete the shuttles while staying on their feet and tagging the line with 1 foot, at the end of each 20-m segment (condition = STD). The shuttle runs were completed with and without a nose clip (no clip = nc; with a clip = clip) under 4 different trial conditions in a randomized order (GRDnc; GRDclip; STDnc; and STDclip), requiring the participants to return on 4 separate occasions separated by 5-7 days. Heart rate was recorded throughout each trial, and the rate of perceived exertion (RPE) was measured at the completion of each shuttle sequence. Pretrial and posttrial lactate and respiratory function measures were also recorded. The general linear model with repeated measures analysis indicated that there was a significant effect for Roll (GRD > STD) (p ≤ 0.05) but not for Clip (p > 0.05) on total time to completion in the trials. There was no significant interaction of the conditions (Roll × Clip) for RPE (p > 0.05). Similarly, there was no significant effect for blood lactate measured 3 minutes post the last shuttle for Roll (p > 0.05) and Clip (p > 0.05). There was a significant main effect on the HR across all 6 time points (i.e., pre, intervals 1-4 and 10 minutes post) (p ≤ 0.05) and for Roll (GRD > STD) (p ≤ 0.05), but not for Clip (p > 0.05). No significant effect of Roll or Clip was found for any of the recorded ventilation measures (p > 0.05). On the basis of these findings, the use of restricted nasal breathing, while performing a high-intensity shuttle sequence as a method of increasing the acute training effect on athletes, is questionable, so strength and conditioning coaches should carefully consider their rationale for using such a training strategy.

Adaptive evolution of the hemagglutinin genes of the H6N1 avian influenza virus in Taiwan, China / 病毒学报

In Taiwan, the first human-infecting H6N1 avian influenza virus was isolated in 2013. To better understand the origin, evolutionary relationship and pathogenesis of the H6N1 virus, we studied the adaptive evolution and evolutionary dynamics of the hemagglutinin (HA) genes of the H6N1 virus in Taiwan. We felt that such studies woud contribute to the further study and control of the virus. Datasets were gained from the Flu and Global Initiative on Sharing All Influenza Data (GISAID) databases. Then, phylogenetic trees and evolutionary dynamics were reconstructed. The evolutionary rate and characterization of adaptive evolution were analyzed by bioinformatic methods. Results indicated that the HA genes of H6N1 in Taiwan were divided into at least five types, and that the new types that the infected human H6N1 belonged to could be local advantage type at present. Evolutionary dynamics revealed the viral population expanded first at the end of 1971, reduced sharply in 2008, and then increased slightly. Three sites were identified under positive selection, suggesting that various sites might increase the adaptive ability of the virus. Eighty-nine sites were under negative selection, revealing that these sites might play an important role in the replication and epidemiology of the virus. Interestingly, site 329 upstream from the cleavage site was also under negative selection, suggesting that this site might be associated with the virulence of H6N1. These data suggest that the HA genes of the Taiwanese H6N1 virus have been undergoing adaptive evolution, and that an outbreak may occur again. Hence, more attention should be paid to the identified sites, to enable timely monitoring and control of a future epidemic.

In vivo migration of mesenchymal stem cells / 中国实验血液学杂志

Mesenchymal stem cells (MSC) have the capacities of low immunogenicity, multiple differentiation, hematopoietic supporting and immunoregulation. And due to their relative ease of availability and ex vivo expansion, the applications of MSC in the prevention and treatment of clinical disease have been rapidly expanded in the recent years. However, increasing investigations indicate that intravenously infused MSC widely distribute to various organs of the recipients. The two intended clinical goals of adoptive cellular therapy reached to the greatest efficiency. Therefore, the ideal candidate cells showed to have the capacity of site-specific relocation in vivo. In this review, the distribution characteristics of infused MSC and the recent research advances on the strategies to enhance targeted migration of MSCs are summarized.

Construction of a bicistronic recombinant adenoviral vector for human interleukin-10 and enhanced green fluorescent protein expression in bone marrow mesenchymal stem cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human interleukin-10 (hIL-10) is a cytokine synthesis inhibitory factor, which is involved in various immune responses. The purpose of this study was to construct an adenoviral vector carrying the hIL-10 gene for expression of biologically active hIL-10 in rat bone marrow mesenchymal stem cells (rMSCs).</p><p><b>METHODS</b>A pSNAV2.0-hIL10 plasmid was used as a template to obtain a hIL-10 cDNA fragment that was subcloned by restriction enzyme digestion and ligation into a pDC316-IRES-EGFP-lacZ alpha plasmid carrying an enhanced green fluorescent protein (EGFP) marker gene. The pDC316-hIL-10-IRES-EGFP plasmid was linearized by PmeI digestion and used to transfect HEK293 packaging cells using the adenovirus packaging system AdMax. Virus particles were amplified by repeatedly infecting HEK293 cells with the seed virus and then purified by ion exchange. After the number of virus particles and titer was determined, rMSCs were infected with the adenoviral vector. The infection rate was determined by fluorescence microscopy and flow cytometry, and hIL-10 protein expression in rMSCs was measured by Western blotting.</p><p><b>RESULTS</b>The virus particle concentration, OD260/280 value and virus titer of the amplified and purified recombinant adenovirus were 3.2 × 10(11) VP/ml, approximately 2.0, and 1.1 × 10(10) TCID50/ml, respectively. Bright green fluorescence was observed by fluorescence microscopy and flow cytometry in the recombinant adenovirus-infected rMSCs. GFP expression was considered the multiplicity of infection (MOI) and was time-dependent. The infection rate was 92.9% at 100 MOI.</p><p><b>CONCLUSIONS</b>A bicistronic recombinant adenoviral vector for hIL-10 and EGFP gene expression were successfully constructed. The infection rate of rMSCs by the adenovirus was high (92.9% at 100 MOI) and the target gene hIL-10 was highly expressed in cells. The present study provides an experimental basis for further research of immunosuppressive therapy using hIL-10. The expression level of hIL-10 protein as detected by Western blotting was also MOI- and time-dependent.</p>

LIGHT expression in peripheral blood of patients with multiple sclerosis / 中华神经医学杂志

[Objective]To observe the changes of level of tumor necrosis factor super-family (TNFSF) member LIGHT in the peripheral blood of patients with multiple sclerosis (MS) and explore the related mechanism.[Methods]Twenty-five patients with MS,admitted to our hospital from November 2009 to May 2011,were chosen in our study;another 22 patients with cerebral infarction (CI) and 27 healthy controls (HC) were chosen.By the use of ELISA and real-time PCR,the plasma LIGHT level and LIGHT mRNA expression in the peripheral blood mononuclear cells (PBMC) were measured;the expanded disability status scale (EDSS) was adopted to reflect the disease severity of MS patients at the time of blood sampling.[Results] MS group had a significantly increased level of plasma LIGHT (133.2 pg/mL) and mRNA expression level of PBMC LIGHT (0.75 relative unit) as compared with HC group (41.2 pg/mL and 0.3) and CI group (79.55 pg/rnL and 0.44,P＜0.05).[Conclusion] There is a dysregulated peripheral LIGHT expression in MS patients;and its abnormal immune response may play an important and complex role in MS-related CNS inflammatory process.

[Effect of acupuncture of different acupoints on immune function in rats with exhausted swimming].

OBJECTIVE: To observe the effect of acupuncture of "Zusanli" (ST 36) on immune function in progressively exhausted swimming rats so as to reveal its mechanism underlying improvement of strenuous exercise. METHODS: Thirty-two SD rats were randomly allocated into control group, strenuous exercise (model) group, acupuncture-Xuehai (SP 10) group, Acupuncture-Zusanli (ST 36) group (n = 8/group). The rats were forced to have a swimming in a water tank for 15-90 min in the first 8 days (once daily), then, a progressively exhausted load swimming 1 - 3 times everyday from day 9 to 13. Bilateral SP 10 and ST 36 were punctured with filiform needles and stimulated with uniform reinforcing and reducing manipulation, once daily, after termination of the swimming and for 13 days. Serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) contents were assayed by using enzyme linked immunosorbent assay. The rat's body weight and the spleen weight were weighted by using an electronic balance for calculating the spleen index (spleen weight /body weight x 100%) after killing the rat under deep anesthesia. RESULTS: Compared with the model group, the time of swimming-induced exhaustion appearing at the first time from day 9 to day 13 in the SP 10 and ST 36 groups was apparently lengthened (P < 0.01). No significant difference was found between SP 10 and ST 36 groups in the time of swimming-induced exhaustion appearing at the first time of the forced swimming. Compared with the control group, the spleen index, serum IFN-gamma contents and IFN-gamma/IL-4 in the model group were decreased significantly (P < 0.01, P < 0.05). In comparison with the model group, the serum IL-4 contents in the SP 10 and ST 36 groups were decreased markedly (P < 0.05, P < 0.01), and serum IFN-gamma content and IFN-gamma/IL-4 in the ST 36 group were increased significantly (P < 0.05, P < 0.01). The IFN-gamma level was significantly higher in the ST 36 group than in the SP 10 group (P < 0.05). No significant differences were found between SP 10 and ST 36 groups in the spleen index, IL-4 and IFN-gamma/IL-4 (P > 0.05). CONCLUSION: Acupuncture at "Zusanli" (ST 36) can lengthen the time of forced swimming-induced exhaustion, and upregulate serum IFN-gamma content and IFN-gamma/IL-4 in exhausted swimming rats, which may contribute to its effect in correcting Th1/Th2 imbalance after strenuous exercise. The effect of acupuncture of ST 36 is superior to that of acupuncture of SP 10.

Expressions of perforin and granzyme-B in CD8+ memory T cell subsets in patients with multiple sclerosis / 中华神经医学杂志

Objective To measure the expressions of cytotoxity-related cytokines in CD8+memory T cell subsets of peripheral blood in patients with multiple sclerosis (MS) and further analyze the relationship between the cytokine levels and MS disease severity. Methods Four-color flow cytometry was employed to detect the proportion of CD8+ memory T cell subsets expressed perforin and granzyme-B in peripheral blood of patients with MS, with other neurological disorders (OND) and of normal control (NC) group. The expanded disability status scale (EDSS) was used to reflect the disease severity at the time of blood sampling. Results Patients with MS had a decreased proportion of effector memory CD8+ T (CD8+ TEM) cells and terminal TEM cells expressed granzyme-B as compared with NC group (P＜0.05). CD8+ TEM cells expressed granzyme-B and perforin were negatively correlated to the scores of EDSS in patients with MS (r=-0.493, P=0.027; r=-0.594, P=0.009). Conclusions CD8+ TEM may be involved in the MS-related CNS inflammatory immune response. The proportion of CD8+ TEM cells expressed perforin and granzyme-B can be used to reflect the pathological severity of MS lesions to some degrees.

Efficacy observation on acupoint catgut embedding therapy combined medication for treatment of chronic urticaria induced by Helicobacter pylori infection / 中国针灸

<p><b>OBJECTIVE</b>To observe the efficacy of acupoint catgut embedding therapy combined medication on chronic urticaria induced by Helicobacter pylori (HP) infection.</p><p><b>METHODS</b>Ninety-two cases were randomly divided into 3 groups, named a medication group (group A, 31 cases), an acupoint catgut embedding group (group B, 30 cases) and a medication combined acupoint catgut embedding group (group C, 31 cases). In group A, the medication was administered orally for antihistamine and anti-HP infection. In group B, catgut embedding was applied on Quchi (LI 11), Xuehai (SP 10), Zusanli (ST 36), etc. In group C, acupoint catgut embedding therapy was applied in combination with medication (medication as group A, acupoint catgut embedding as group B). After 3-month treatment, the efficacy, recurrence rate and HP negative rate were compared among 3 groups.</p><p><b>RESULTS</b>Separately, the effective rates of group A, B, C were 61.3% (19/31), 53.3% (16/30) and 90.3% (28/31); the recurrence rates were 27.3% (3/11), 33.3% (3/9) and 5.9% (1/17); and HP negative rates were 31.3% (10/31), 26.7% (9/30) and 77.4% (24/31). The clinical efficacy and HP negative rate in group C were superior to those in group A and B (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>Acupoint catgut embedding therapy combined medication is significant in efficacy and low in recurrence rate in treatment of chronic urticaria caused by HP infection.</p>

Treatment with 89SrCl and Sodium Ibandronate for pain relief of multiple bone metastases / 中华核医学杂志

Objective To evaluate the palliative effect on pain relief in patients with multiple bone metastases treated with 89SrCl2 together with Sodium Ibandronate,Sodium Ibandronate alone and 89SrCl2 alone. Methods Eighty-four patients with bone pain secondary to bone metastases were divided into three groups. Thirty patients were treated with combined 89SrCl2 and Sodium Ibandronate,26 with 89SrCl2 alone and 28 with Sodium Ibandronate alone. The x2 test was used in data analysis. Results The overall palliative pain relief rate in the combined treatment group was 96.6 % (29/30). For the groups using Sodium Ibandronate or 89SrCl2 only,the palliative rates were 71.4% (20/28) and 73.1% (19/26),respectively. There are statistically significant differences between the combined treatment group and the other 2 groups with single treatment modalities in the overall palliative pain relief rate (x2 = 7.497 ),in terms of improvement in (1) whole body Karnofsky performance status (KPS) score (80.0% (24/30) vs 50.0% (14/28)/53.8% (14/26),x2 =35.476) and (2) focal palliative rate (47.6% (50/105) vs 11.2% (11/98)/22.2% (20/90),x2 =6. 564,all P ＜ 0. 05 ). Conclusions Combined treatment with 89 SrCl2 and Sodium Ibandronate is more effective than single treatment modalities to relieve bone pain seccondary to multiple bone metastases.