Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Combining biofeedback based on virtual reality technology with transcranial magnetic stimulation aids the recovery of dysphagic stroke survivors / 中华物理医学与康复杂志

Objective:To observe the effect of combining biofeedback therapy (BFT) based on virtual reality technology with repeated transcranial magnetic stimulation (rTMS) on dysphagia among stroke survivors.Methods:Eighty patients were randomly divided into a control group, an rTMS group, a BFT group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the rTMS and BFT groups were given those treatments, while the combined treatment group was given both for 4 weeks. Swallowing function was evaluated before and after the treatment using the standardized swallowing assessment (SSA) and the functional oral intake scale (FOIS). Videofluoroscopy was used to quantify the subjects′ oral and pharyngeal phases and their aspiration status.Results:Significant improvement was observed in the average FOIS and SSA scores, as well as in the average oral and pharyngeal phases and in aspiration. The combined treatment group′s results were significantly better in all those aspects than those of the other 3 groups.Conclusion:The combined application of biofeedback therapy based on virtual reality technology and repeated transcranial magnetic stimulation can improve the swallowing function of stroke survivors with dysphagia. It is worthy of clinical promotion.

Electroacupuncture enhances the effectiveness of electrical stimulation in treating spastic foot drop / 中华物理医学与康复杂志

Objective:To observe the clinical effect of combining four-channel electrical stimulation with electroacupuncture of the antagonistic muscles in treating post-stroke spastic foot drop.Methods:Ninety stroke survivors with spastic foot drop were randomly divided into a control group, an electrical stimulation group and an observation group, each of 30. In addition to routine rehabilitation training, the electrical stimulation group was given four-channel electrical stimulation for 4 weeks, the electrical stimulation was delivered with a pulse duration of 200μs and an intensity of motor threshold at 30Hz, while the observation group also received electroacupuncture of the antagonistic muscle. Before and after the treatment, the three groups were evaluated using the clinical spasticity index (CSI). Stride frequency, stride length, and the supporting and swing phases on the affected side were also measured. Electromyography (EMG) was also conducted.Results:After the treatment, the average CSI scores of all groups had decreased significantly, with that of the observation group significantly lower than the electrical stimulation group and control group′s averages. The average gait descriptors of the three groups had also improved significantly, with significantly greater improvement in the observation group than in the other two. The average H reflex latency was significantly longer and Hmax/Mmax was significantly smaller in all three groups, but the observation group′s average values were again significantly better than those of the electrical stimulation group.Conclusion:Electroacupuncture of the antagonistic muscle enhances the effectiveness of four-channel electrical stimulation in relieving foot drop symptoms and improving gait after a stroke.

Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis

Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and the confronting "Warburg effect" compromise the efficacy of hypoxia alleviation. Herein, we construct a cascade enzyme-powered nanomotor (NM-si), which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy. Catalase (Cat) and glucose oxidase (GOx) are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor (NM), with hexokinase-2 (HK-2) siRNA further condensed (NM-si). The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H

Parameters optimization in Heparin affinity chromatography purification of human coagulation factor Ⅸ / 中国输血杂志

【Objective】 To optimize the purification conditions of heparin affinity chromatography in the purification of human coagulation factor Ⅸ by response surface method and establish the optimal chromatography process parameters. 【Methods】 The effect of sample loading temperature on purification efficiency was analyzed through single factor test. Three-factor three-level response surface method was used to optimize the chromatographic elution conditions. The Folin phenol method and the automatic hemagglutination analyzer were used to determine the total protein content and human coagulation factor Ⅸ titer, respectively. The purification effect was evaluated by activity index and process recovery rate. 【Results】 The optimized optimal chromatographic conditions were loading at 5 ℃, washing 4 CV, eluent formulation of sodium citrate 20 mmol/L, arginine hydrochloride 18.7 mmol/L, NaCl 611.6 mmol/L and pH 7.5; under this optimal setting, the recovery rate of the chromatographic process was (46.6±2.9) %, titer of factor Ⅸ rated to (68.4±4.7) IU/mL and specific activity was (62.8±3.3) IU/mg. 【Conclusion】 The optimized parameters of heparin affinity chromatography process by response surface method can produce better purification effect on human coagulation factor Ⅸ.

The construction of nasal cavity-mimic M-cell model, design of M cell-targeting nanoparticles and evaluation of mucosal vaccination by nasal administration

In order to better evaluate the transport effect of nanoparticles through the nasal mucosa, an nasal cavity-mimic model was designed based on M cells. The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model. The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability. The differentiation of M cells was observed by up-regulated expression of Sialyl Lewis A antigen (SLAA) and integrin 1, and down-regulated activity of alkaline phosphatase. After targeting M cells with iRGD peptide (cRGDKGPDC), the transport of nanoparticles increased. , the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration. In the evaluation of immune effect , the nasal administration of OVA-PLGA/iRGD led to more release of IgG, IFN-, IL-2 and secretory IgA (sIgA) compared with OVA@PLGA group. Collectively, the study constructed M cell model, and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.

The progress and perspective of nanoparticle-enabled tumor metastasis treatment

As one of the most serious threats to human being, cancer is hard to be treated when metastasis happens. What's worse, there are few identified targets of metastasis for drug development. Therefore, it is important to develop strategies to prevent metastasis or treat existed metastasis. This review focuses on the procedure of metastasis, and first summarizes the targeting delivery strategies, including primary tumor targeting drug delivery, tumor metastasis targeting drug delivery and hijacking circulation cells. Then, as a promising treatment, the application of immunotherapy in tumor metastasis treatment is introduced, and strategies that stimulating immune response are reviewed, including chemotherapy, photothermal therapy, photodynamic therapy, ferroptosis, sonodynamic therapy, and nanovaccines. Finally, the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are discussed.

Microecology research: a new target for the prevention of asthma / 中华医学杂志(英文版)

The incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of "when and how" to regulate microbiome is still needed.

Advances in tumor microenvironment responsive and regulatory drug delivery system / 药学学报

The complexity of tumor microenvironment brings both challenges and opportunities for targeted drug delivery. On the one hand, using the special characteristic as stimuli, we can construct a variety of responsive drug delivery systems for tumor targeting. On the other hand, the abnormal vasculature and dense extracellular matrix in solid tumor become formidable barriers to the nanoparticles delivery, which greatly reduces the drug delivery efficiency. Lots of researches focus on regulating the tumor microenvironment to make it more conducive to drug delivery. In this review, we will highlight the recent advances both in tumor microenvironment responsive nano-drug delivery systems design and tumor microenvironment regulation to improve tumor targeted delivery efficiency, and discuss the existing problems and future development.

Theranostic nanoparticles with tumor-specific enzyme-triggered size reduction and drug release to perform photothermal therapy for breast cancer treatment

Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency, nanoparticles need to change size so as to fully utilize the enhanced permeability and retention (EPR) effect of solid tumor, which is the golden principle of nanoparticles used for cancer treatment. Herein, we employed cationic small-sized red emission bovine serum albumin (BSA) protected gold nanocluster (AuNC@CBSA, 21.06 nm) to both load indocyanine green (ICG) and act as imaging probe to realize theranostic. Then AuNC@CBSA-ICG was fabricated with negatively charged hyaluronic acid (HA) to form AuNC@CBSA-ICG@HA, which was about 200 nm to easily retain at tumor site and could be degraded by tumor-specific hyaluronidase into small nanoparticles for deep tumor penetration. The HA shell also endowed AuNC@CBSA-ICG@HA with actively targeting ability and hyaluronidase-dependent drug release. Furthermore, the quenching and recovery of fluorescence revealed the interaction between ICG and carrier, which was essential for the investigation of pharmacokinetic profiles. No matter or , AuNC@CBSA-ICG@HA showed markedly anti-tumor effect, and could suppress 95.0% of tumor growth on mice breast cancer model. All results demonstrated AuNC@CBSA-ICG@HA was potential for breast cancer therapy.

Effect of Sling Exercise Therapy on Chronic Nonspecific Low Back Pain / 中国康复理论与实践

Objective:To observe the effect of sling exercise therapy on chronic nonspecific low back pain. Methods:From February, 2017 to February, 2018, 84 patients with chronic nonspecific low back pain were randomly divided into control group and observation group, with 42 cases in each group. The observation group was treated with the combination of the sling exercise therapy and acupuncture, and the control group only received acupuncture. They were assessed with Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) before treatment, one month after treatment and at three-month follow-up. Results:Before treatment, there was no statistically significant difference in the scores of VAS and ODI between two groups (t < 1.638, P > 0.05). One month after treatment and at three-month follow-up, the scores of VAS and ODI decreased in both groups (P < 0.01). Compared with one month after treatment, the scores of VAS and ODI increased in the control group at three-month follow-up (t > 2.219, P < 0.05), however, no difference was found in the observation group (t < 1.738, P > 0.05). One month after treatment, the scores of VAS and ODI were lower in the observation group than in the control group (t > 3.535, P < 0.001). Conclusion:Sling exercise therapy combined with acupuncture is superior to simple acupuncture in treating chronic nonspecific low back pain, and the curative effect is persistent.

Expression of Notch signaling pathway in cultured human osteoarthritic articular chondrocytes / 局解手术学杂志

Objective To explore the role of Notch signaling pathway in the matrix synthesis of osteoarthritis cartilage cell and its possi -ble mechanism.Methods Selected the femoral condylar cartilage of 8 patients who were admitted into our hospital and treated with knee joint replacement as the observation group,while the normal femoral condyle cartilage of one patient with above-knee amputation was selected as the control group.The specimens were given histological examination or cell isolation culture and detection.The cultured cells were divided into 4 groups,namely the normal cartilage cells,OA cartilage cells,OA cartilage cells with γ-secretase inhibitor DAPT,OA cartilage cells with recombinant human proteins Delta4.Then immunohistochemistry and Western blot were used for detecting the expression of Notch -1,Notch-3, Jagged-1,Jagged-2 and HES5 in chondrocytes in vitro.Results The expression of Notch signaling pathway and the phenotype of cartilage cells changed in the osteoarthritis.The expression of Notch-1,Jagged-1,Jagged-2 and HES5 were activated.γ-secretase inhibitor DAPT (20 μmol/L)could inhibit the expression of Notch-1,HES5,Jagged-1,and Notch-3,while it had no obvious effect on the expreesion of Jag-ged-2.Recombinant human proteins Delta 4(100 ng/μL)could promote the expression of Notch-1,Jagged-2,and HES5,and it had no obvi-ous effect on the expreesion of Jagged-1 and Notch-3.Conclusion The expression of Notch signaling pathway of cartilage cells changed in the osteoarthritis.DLL4 can activate the Notch signaling pathway and DAPT can inhibit the Notch signaling pathway.

Regulatory factors and modulation mechanisms of functions of ovarian germline stem cell niche / 上海交通大学学报（医学版）

With increasing age in women, the ovarian function declines, which leads to decreased follicle generation, declined female fertility and age-related diseases ultimately. Female germline stem cells are epithelial cells existing on the ovarian surface, which can divide into new stem cells symmetrically and differentiate into germ cells and granulosa cells asymmetrically. The discovery of female germline stem cells brings much hope for the post-natal renewal of oocytes and solving female infertility problems. Ovarian germline stem cell niche in which female germline stem cells live is the surrounding microenvironment which plays an essential role in maintaining the function of female germline stem cells. Many factors including nutrition supply, protein, cytokines and signaling pathways can control the biological characters of female germline stem cells, and also influence their proliferation and differentiation. This paper reviewed the knowledge about the influencing factors and regulatory mechanisms of the function of ovarian germline stem cell niche.

Manipulative reduction and small splint fixation combined with micromovement exercise for treatment of humeral shaft fractures / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the therapeutic efficacy of bone-setting manipulative reduction and small splint fixation combined with micro-movement theory exercise for treatment of humeral shaft fractures.</p><p><b>METHODS</b>From March 2011 to February 2014, 64 cases of humeral shaft fractures were treated by bone-setting manipulative reduction and small splint fixation including 28 males and 36 females with an average age of 38.1 years old ranging from 22 to 67 years old. According to the classification of AO/OTA, there were 10 cases of type A1, 12 cases of type A2,11 cases of type A3,10 cases of type B1,12 cases of type B2, 7 cases of type B3, 2 cases of type C1, 1 case of type C2, 1 case of type C3. After close reduction early functional exercise performed according to micro-movement theory. All patients had no other parts of the fractures, neurovascular injury, and serious medical problems. Patients were followed up for fracture healing, shoulder and elbow joint function recovery, and curative effect.</p><p><b>RESULTS</b>All patients were followed up from 10 to 12 months with an average of 10.3 months. Of them, 2 cases had a small amount of callus growth at 3 months after close reduction, so instead of operation; 2 cases appeared radial nerve symptoms after close reduction ,so instead of operation. Other patients were osseous healing, the time was 8 to 12 weeks with an average of 10.2 weeks. After osseous healing, according to Constant-Murley score system ,the average score was (93.5 ± 3.2) points, the result was excellent in 29 cases, good in 29 cases, fair in 6 cases, excellent and good rate was 90.3%; according to the Mayo score system, the average score was (93.7 ± 4.2) points, the result was excellent in 35 cases, good in 23 cases, fair in 6 cases, excellent and good rate was 91.9%.</p><p><b>CONCLUSION</b>Bone-setting manipulative reduction and small splint fixation combined with micromovement theory exercise for treatment of humeral shaft fractures has advantage of positive effect, easy and inexpensive method, the treatment has relevant scientific basis and practical value, it can effectively reduce complications, promote patients early recovery.</p>

2-Methylthio-adenosine-5'-triphosphate inhibits ventricular arrhythmogenesis in rabbits with chronic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects and related mechanisms of 2-methylthio-adenosine-5'-triphosphate (2-MeSATP), an important extracellular agonist that activates receptors for purine nucleotides (P2XR), on ventricular arrhythmias in rabbits with chronic heart failure (CHF).</p><p><b>METHODS</b>The male New Zealand rabbits were divide into control (n=12), CHF (n=12) and CHF+2-MeSATP groups (2-MeSATP, n=12). CHF was induced by isoproterenol injection (0.3 mg·kg⁻¹·d⁻¹ for 3 weeks) and rabbits were observed 6 months later. The main cardioelectrophysiological parameters and ventricular arrhythmias were tested by recording monophasic action potential (MAP) with burst-pacing (BCL) in rabbits in vivo. The transient outward potassium current (Ito) was recorded via whole-cell patch clamp technique and the fluorescence intensity of intracellular free Ca²⁺ was detected with Flup-3/AM loading by the laser scanning confocal microscope in enzymatically dissociated single rabbet ventricular myocytes.</p><p><b>RESULTS</b>CHF rabbits developed severely clinical CHF signs and symptoms, reduced left ventricular ejection fraction and fractional shortening as well as enlarged end-diastolic dimension. Compared with CHF group, APA and MaxdV/dt were significantly increased, while APD20, APD50 and APD90 were significantly reduced in 2-MeSATP group (all P<0.01). Moreover, 2-MeSATP could obviously shorten BCL induced ventricular arrhythmias, and decrease deducibility and persistence time of ventricular arrhythmias with burst-pacing in 2-MeSATP group in vivo (all P<0.05). With voltage clamp model, 2-MeSATP could significantly increase the current density of Ito in different command potential in CHF ventricular myocytes (all P<0.01). When holding potential was set at -50 mV and command potential was set at +50 mV, the current densities of Ito increase was more significant in 2-MeSATP group than that in CHF group ((11.79 ± 4.51) pA/pF vs. (7.94 ± 3.53) pA/pF, P<0.01). 2-MeSATP could completely change the I-V curve upward without changing the I-V curve direction in CHF ventricular myocytes. The fluorescence intensities of intracellular free Ca²⁺ increase was more significant in 2-MeSATP group compared to CHF group ((1 291.98 ± 123.31) µmol/L vs. (793.59 ± 114.65) µmol/L, P<0.01).</p><p><b>CONCLUSION</b>2-MeSATP as a potent agonist acting on P2XR could significantly shorten APD, increase heart rate and improve cardiac performance as well as decrease the susceptibility of ventricular arrhythmias in this rabbit CHF model. Our results suggest that Ito increase and sarcoplasmic reticulum uptake Ca²⁺ enhancement as well as dynamic balance of intracellular Ca²⁺ cycling sustenance might linked to the beneficial effects of 2-MeSATP in this CHF model.</p>

Cannulated screw combined with buttress plate for the treatment of transarticular shear fractures of the distal humerus / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical outcomes of cannulated screw combined with buttress plate in treating transarticular shear fractures of the distal humerus.</p><p><b>METHODS</b>From July 2008 to December 2011, 17 patients with shear fractures of the distal humerus were treated with cannulated screw combined with buttress plate. Among them, included 10 males and 7 females aged from 20 to 59 years old (mean 36.5). All the fractures were classified into type I (8 cases), type II (1 case), type III (3 cases) and type IV (5 cases) according to Bryan-Morrey and McKee classification. According to AO/ASIF classification, 10 cases were type 13B3.1, 7 cases were type 13B3.3; according to Dubberley classification, 5 cases with type 1A, 2 cases with type 1B, 2 cases with type 2A, 2 cases with type 2B, 4 cases with type 3A, 2 cases with type 3B. There were 12 cases with fresh injuries, 4 cases with old injuries. All fractures were closed injuries. Complications and range of motion of elbow were observed, and clinical efficacy were evaluated by Broberg-Morrey standard.</p><p><b>RESULTS</b>All patients were followed up with a mean time of 21.3 months (ranged, 18 to 24). All fractures obtained bone healing from 10 to 15 weeks with a mean of 12.5 weeks. No malunion or delayed healing occurred. Two cases occurred ossification in lateral collateral ligament attachment. 2 cases occurred heterotopic ossification in the capitellum in front of capsule joint. The range of elbow extension was (16 +/- 7) degrees, flexion was (115 +/- 9) degrees, the average are of pronation and supination was (65 +/- 5) degrees and (60 +/- 5) degrees respectively. According to Broberg-Morrey standard, there were excellent in 7 cases, good in 8 cases, fair in 2 cases, and average score was 92.44 +/- 4.64.</p><p><b>CONCLUSION</b>For transarticular shear fractures of the distal humerus, classification should be performed according to preoperative X-ray and CT, cannulated screw and buttress plate combined and early function rehabilitation could recover elbow function.</p>

Arthroscopic surgery for the treatment of stiff elbow / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical results of arthroscopic surgery for the treatment of stiff elbow.</p><p><b>METHODS</b>From October 2010 to December 2012, 27 patients with stiff elbow were treated with arthroscopic debridement and joint capsular releasing. There were 18 males and 9 females, ranging in age from 24 to 54 years old, with an average of 35.7 years old. Analgesia and rehabilitation were necessary after operation. Mayo criteria system was used to evaluate therapeutic effects.</p><p><b>RESULTS</b>All the patients were followed up, and the duration ranged from 12 to 18 months, with a mean of 13.5 months. The mean maximum flexion angle of patients improved from preoperative (61.5 ± 30.1) degrees to postoperative (102.5 ± 20.1) degrees; and the mean maximum extension angle improved from preoperative (34.8 ± 12.1) degrees to postoperative (16.3 ± 16.1) degrees; the average total range of motion improved from preoperative (34.2 ± 21.0) degrees to postoperative (84.9 ± 9.2) degrees. According to the Mayo criteria system, the average score increased from preoperative 60.5 ± 13.4 to postoperative 88.7 ± 6.3; ten patients got an excellent result, 13 good and 4 fair.</p><p><b>CONCLUSION</b>Arthroscopic surgery to treat elbow stiffness has such advantages as minimal invasion, less blood loss, fast recovery, and clear visualization, which is effective to improve elbow joint functions with less complications.</p>

Role of mitochondrial damage during cardiac apoptosis in septic rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats.</p><p><b>METHODS</b>Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity.</p><p><b>RESULTS</b>Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection (P < 0.05). The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge.</p><p><b>CONCLUSIONS</b>Septic challenge induced myocardial apoptosis and mitochondrial damage. Furthermore, mitochondrial damage via alteration of defenses against reactive oxygen species might play an important role in myocardial apoptosis during sepsis.</p>

No association between 3 polymorphisms of transforming growth factor beta3 gene and essential hypertension in Chinese / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate possible association between the single nucleotide polymorphisms (SNPs) of transforming growth factor beta3 (TGF-beta3) gene and essential hypertension (EH) in Chinese.</p><p><b>METHODS</b>The promoter region, exons, as well as part of the introns of TGF-beta3 gene were sequenced by a fluorescent labeling automatic sequencing method to detect and characterize the SNPs in 24 DNA samples from a Chinese population. Then we conducted a case-control study using 396 patients with hypertension (case) and 214 nomortensive subjects (control). The three SNPs including Thr63Asn, SS5608219 and SS5608220 were genotyped by PCR-RFLP or real-time allele-specific PCR in subjects studied.</p><p><b>RESULTS</b>Seven SNPs in the exons, introns and 3'untranslated region (3'UTR) of TGF-beta3 gene were identified. Among them, 2 SNPs were found to be novel genetic variants and one of the two located in the exon 1 and produced substitution of amino acid. However, no differences were found between hypertensives and nomortensives in genotype distribution and allele frequency of SS5608219, Thr63Asn or SS5608220 polymorphisms.</p><p><b>CONCLUSIONS</b>Two novel SNPs of TGF-beta3 gene were identified in Chinese. One of them produces a threonine to asparagines substitution in codon 63 (Thr63Asn). But no association was found between TGF-beta3 gene polymorphisms and EH in Chinese.</p>

Clinical significance of the anticardiolipin antibodies in patients with hemorrhagic fever with renal syn-drome / 中华传染病杂志

Objective To investigate the clinical significance of anticardiolipin antibodies (ACA)in patients with hemorrhagic fever with renal syndrome(HFRS).Methods The serum ACA- IgM and ACA-IgG in 175 cases of renal diseases and 50 healthy cases were detected by enzyme-linked immunosorbent assay(ELISA). The positive rates of ACA were calculated and compared among different groups.Results The positive rates of ACA-IgM and ACA-IgG in control group were both 0 (0/50),while they were 85.2%(46/54)and 24.1%(13/54)respectively in patients with HERS. 25.0%(13/52)and 21.2%(11/52)respectively in patients with lupus nephritis and 13.0%(9/69) and 8.7%(6/69)respectively in patients with nephrotic syndrome.The poshive rate of ACA lgM in patients with HFRS was higher than that in control group,lupus nephritis group and nephritic syn- drome group(P