Generation and phenotypic characterization of S100A9 gene knockout mice by CRISPR/Cas9-mediated gene targeting / 生理学报

S100 calcium binding protein A9 (S100A9) is involved in a variety of biological processes such as inflammation and tumor cell migration and invasion regulation. The purpose of this study was to construct S100A9 gene-edited mice by using CRISPR/Cas9 technology, thereby providing an animal model for exploring the biological functions of this gene. According to the S100A9 gene sequence, the single-stranded small guide RNA (sgRNA) targeting exons 2 and 3 was transcribed in vitro, and a mixture of Cas9 mRNA and candidate sgRNA was injected into mouse fertilized eggs by microinjection. Early embryos were obtained and transferred to surrogate mice, and F

Ethacrynic acid inhibits airway smooth muscle contraction in mice / 生理学报

The aim of this study was to investigate the inhibitory effect and the underlying mechanism of ethacrynic acid (EA) on the contraction in mice. BL-420S force measuring system was used to measure the tension of mouse tracheal rings. The whole cell patch clamp technique was utilized to record the channel currents of airway smooth muscle (ASM) cells. The calcium imaging system was used to determine the intracellular Ca concentration ([Ca]) in ASM cells. The results showed that EA significantly inhibited the high K (80 mmol/L) and acetylcholine (ACh, 100 µmol/L)-induced contraction of mouse tracheal rings in a dose-dependent manner. The maximal relaxation percentages were (97.02 ± 1.56)% and (85.21 ± 0.03)%, and the median effective concentrations were (40.28 ± 2.20) μmol/L and (56.22 ± 7.62) μmol/L, respectively. EA decreased the K and ACh-induced elevation of [Ca] from 0.40 ± 0.04 to 0.16 ± 0.01 and from 0.50 ± 0.01 to 0.39 ± 0.01, respectively. In addition, EA inhibited L-type voltage-dependent calcium channel (LVDCC) and store-operated calcium channel (SOCC) currents in ASM cells, and Ca influx. Moreover, EA decreased the resistance of the respiratory system (Rrs) in vivo in mice. These results indicated that EA inhibits LVDCC and SOCC, which results in termination of Ca influx and decreases of [Ca], leading to relaxation of ASM. Taken together, EA might be a potential bronchodilator.

Dental pulp stem cells in tissue engineering: application and development / 中国组织工程研究

BACKGROUND: As a special source of stem cells, dental pulp stem cells (DPSCs) make much progress in the development of tissue engineering field due to their high proliferation and self-renewal ability. In the certain conditions DPSCs can be induced to differentiate into a variety of specialized tissue cells, providing a new way for tissue engineering development. OBJECTIVE: To review the main progress in the DPSCs biological characteristics, original source, isolation method, and its related application in tissue engineering research. METHODS: "Dental pulp stem cell, differentiation, regenerative medicine, tissue engineering" in English and Chinese were termed as the keywords to search relevant articles about DPSCs and tissue engineering published from 2005 to 2017 in PubMed, Medline, WanFang, and CNKI databases. After removal of repetitive or irrelevant articles, 66 articles were finally reviewed. RESULTS AND CONCLUSION: With the development of tissue engineering and regenerative medicine, the effective combination of DPSCs and tissue engineering scaffolds have be further achieved. Recent studies on DPSCs focus on the properties of DPSCs differentiating into odontoblasts and osteocytes/osteoblasts and on the potential of nerve repair, vascular remodeling, corneal reconstruction and chondrogenic differentiation.

Observation of serum protein fingerprinting in primary liver cancer patients of different Chinese medical syndromes before and after interventional treatment / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore changes of serum protein fingerprinting in primary liver cancer (PLC) patients of different Chinese medical syndromes before and after interventional treatment detected by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS).</p><p><b>METHODS</b>Totally 154 PLC patients were assigned to 5 groups, i.e., Gan depression syndrome (GDS, 37 cases), Pi deficiency syndrome (PDS, 45 cases), dampness heat syndrome (DHS, 18 cases), blood stasis syndrome (BSS, 28 cases), yin deficiency syndrome (YDS, 26 cases). The mass spectra of serum proteins was analyzed by using SELDI-TOF-MS. Then the correlation between Chinese medical syndrome types and the mass spectra of serum proteins was explored before and after interventional treatment.</p><p><b>RESULTS</b>Compared with the healthy control group, the expression of serum proteins peak was down-regulated in GDS with M/Z being 6 589 and 4 182 Da, in DHS with M/Z being 5 710 Da, in YDS with M/ Z being 6 992 Da, while it was up-regulated in PDS with M/Z being 5 816 Da and in BSS with M/Z being 4 297 Da, showing statistical difference (P < 0.01). Compared with before intervention, the expression of serum proteins peak was down-regulated in GDS with M/Z being 6 589 and 4 182 Da, in PDS with M/Z being 5 816 Da, in DHS with M/Z being 5 710 Da in BSS with M/Z being 4 297 Da, while it was up-regulated in YDS with M/Z being 6 992 Da, showing statistical difference (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>There was statistical difference in changes of serum protein fingerprinting in PLC patients of different Chinese medical syndromes before and after interventional treatment.</p>

Inhibitory effect of quercetin preconditioning on tunicamycin-induced apoptosis in macrophages and its mechanism / 生理学报

The purposes of the present study were to investigate the inhibitory effect of quercetin (QUE) preconditioning on endoplasmic reticulum stress (ERS) inducer tunicamycin (TM)-induced apoptosis in RAW264.7 macrophages and the underlying molecular mechanisms. RAW264.7 cells were pretreated with different concentrations (20, 40, and 80 μmol/L) of QUE for 30 min and then treated with TM (5 mg/L) for 12 h. Cell viability and apoptosis were determined using MTT assay and Annexin V-FITC apoptosis detection kit, respectively. The nuclear translocation of activating transcription factor 6 (ATF6) in cells was detected by immunofluorescence analysis and Western blot. Protein and mRNA expressions of C/EBP homologous protein (CHOP) and Bcl-2 were examined by Western blot and real-time PCR, respectively. The results showed that TM reduced cell viability and induced apoptosis in RAW264.7 macrophages. The cytotoxic effects of TM were significantly inhibited by QUE pretreatment at the concentrations of 40 and 80 μmol/L. Interestingly, we found that QUE also significantly suppressed the TM-induced translocation of ATF6, an ERS sensor, from the cytoplasm to the nucleus. In addition, exposure of RAW264.7 macrophages to TM resulted in a significant increase of the expression of CHOP, a transcription factor regulated by ATF6 under conditions of ERS, as well as a decrease of Bcl-2 at transcript and protein levels. QUE blocked these effects in a dose-dependent manner. These data indicate that QUE can protect RAW264.7 cells from TM-induced apoptosis and that the mechanism at least partially involves its ability to inhibit the ATF6-CHOP signaling pathway.

Analysis of characteristics of acute poisoning caused by various poisons in Guangxi, China / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the characteristics of acute poisonings caused by various poisons in Guangxi, China.</p><p><b>METHODS</b>A retrospective investigation was performed in 5859 cases of acute poisonings who were admitted to 63 hospitals in 11 cities, as well as 531 types of poisons involved. The poisons were categorized into 6 groups; each group of cases was stratified by the rural or urban settings, frequency of poisoning, and cause of poisoning to analyze the numbers of cases and constituent ratios.</p><p><b>RESULTS</b>Most types of poisons (68.74%) belonged to drugs (217 types) and pesticides (148 types). Most cases of poisonings (61.63%) were caused by pesticides (n = 2547) and chemicals (n = 1064). Pesticides, poisons of plant origins, and poisons of animal origins were responsible for most of the cases in rural settings; 88.46%, 79.10%, and 66.74% of the cases of these poison categories happened in rural settings. Chemicals, drugs, and other poisons were responsible for most of the cases in urban settings; 70.20%, 61.74%, and 63.73% of the cases of these poison categories happened in urban settings. The numbers of cases in 5-year-poisoning groups were the highest in all categories of poisons, accounting for 85.24%, 88.57%, 55.16%, 70.79%, 68.36%, and 66.44%of cases of respective categories. Most cases of poisonings by chemicals, poisons of animal origin, and other poisons were accident-related (86.24%, 72.66%, and 46.71%of the poison categories). Most cases of poisonings by pesticides and drugs were suicide-related (59.39% and 33.52% of the poison categories). Most cases by poisons of plant origin were caused by accidental ingestion (70.36% of the poison category).</p><p><b>CONCLUSION</b>Most of the acute poisonings in Guangxi area are caused by pesticides and chemicals; the most common causes of poisoning are accidents, accidental ingestion, and suicide. There are significant differences in the causes of acute poisonings between the urban and rural settings.</p>

Cardiac inwardly rectifying potassium channel and arrhythmias / 生理学报

The cardiac inwardly rectifying potassium channel (I(K1)), which is mainly expressed in mammalian atrial and ventricular myocytes, has been considered as the primary conductance controlling the resting potential (RP) and permitting a significant repolarizing current during the terminal phase of action potential. Therefore, I(K1) is highly influential on the RP, and the modulation of I(K1) would likely have profound effects on cardiac excitability and arrhythmogenesis. This article may shed light on the fundamental properties of cardiac I(K1), the mechanisms of inward rectification and I(K1) subunits composition. Furthermore, the article discusses the role of I(K1) in ventricular excitability and arrhythmogenesis and explores the possibility of modulating I(K1) as an antiarrhythmic mechanism. In fact, both blocking and enhancing I(K1) could be antiarrhythmic, but have proarrhythmic potential at the same time. Action potential duration (APD) prolongation has been accepted as an important antiarrhythmic strategy with some evidence in animal models of arrhythmogenesis that I(K1) blockade can prolongate APD and be antiarrhythmic. However, the potential of I(K1) blockade has not resulted in the development of specific I(K1) blockers used clinically. Safety concerns are probably the main reason, and the therapeutic potential for I(K1) blockers seems somewhat small. On the contrary, the up to date reports indicate that moderately activating I(K1) and hyperpolarizing the RP which has been depolarized by pathologic injury are to be feasible and effective to alleviate some kinds of ventricular arrhythmias.

Static viscoelastic properties of bionic UHMWPE articular cartilage material / 医用生物力学

Objective To evaluate the static viscoelastic properties of the porous gradient UHMWPE material by the creep, stress relaxation and creep recovery tests. Method The porous gradient UHMWPE material was prepared by the template leaching (T-L) method. The porous structure was characterized by scanning electron microscopy(SEM) and the porosity and pore distribution of porous layer were measured by a pressure mercury analyzer. The creep, stress relaxation and creep recovery properties were tested by the experimental determination of flat indentation. Results The porous layer of T-L UHMWPE was well bonded with the substrate material. With the increase of NaCl content, the porosity and pore size distribution scope improved clearly. Creep deformation and modulus presented a nonlinear increase with time and the stress and modulus of stress relaxation showed a nonlinear decrease with time. The buffering capacity for impact loads of porous gradient UHMWPE was significantly higher than the compact UHMWPE. Experimental results showed that the creep recovery properties of the reasonable porosity of U50 and U60 samples were almost similar to the compact UHMWPE material. But the higher porosity caused the increase of the plastic deformation. Conclusions The porous structure of UHMWPE effectively increased the elastic property and strain response sensitivity, which may be beneficial to improve the lubrication of frictional contact surfaces and reduce the wear of artificial joints.

Influence of the insert design on clinical results and kinematics of the knee after total knee arthroplasty / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the influence of the insert design of knee prosthesis on clinical results and kinematics of the knee after total knee arthroplasty (TKA).</p><p><b>METHODS</b>Forty-two knees in 28 patients with knee osteoarthritis undergoing TKA using the GENESIS II from July 2007 to June 2009 were included in this study, mean follow-up of 27.7 months. The cases were divided into 2 groups according to the type of insert, one was high flexion insert group (23 knees) and the other was standard insert group (19 knees). Two groups were compared by clinical ratings of knee function. The motion of flexion and extension of the two groups was observed by cyclic fluoroscopy and the data was analyzed by mapping software. The influence of the insert design of knee prosthesis on kinematics of the knee after TKA was investigated by comparing the parameters of the two groups during the movement of knee joint, including femoral roll back and extensor mechanism arm.</p><p><b>RESULTS</b>The range of motion of standard insert group and high flexion insert group was 120° and 123° respectively with no difference between them. There was no difference of knee society clinical rating system in both groups. Feller score of high flexion insert group was higher than the standard insert group, the difference was significant statistically (P = 0.012). In the imaging measurement, the two groups had no differences in femoral rollback and extensor mechanism arm during the 0 to 120° range of movement. The two groups appeared significant statistically (P = 0.034) in the extensor mechanism arm when flexion extended to 130°.</p><p><b>CONCLUSIONS</b>The high flexion improved design may play a certain role on reducing anterior knee pain and improving knee function after TKA. However, the improved design may be reduced the extensor mechanism arm when high flexion, so that affecting the work ability of quadriceps.</p>

Activation of δ-opioid receptors inhibits L-type Ca(2+) current and transient outward K(+) current in rat ventricular myocytes / 生理学报

In the present study, whole-cell patch-clamp technique was used to observe the effects of SNC162, a selective agonist of δ-opioid receptors, on L-type Ca(2+) current (I(Ca-L)) and transient outward K(+) current (I(to)) in rat ventricular myocytes. The results showed that SNC162 significantly inhibited I(Ca-L) and I(to) in rat ventricular myocytes. The maximal inhibition rate of I(Ca-L) and I(to) reached (46.13±4.12)% and (36.53±10.57)%, respectively. SNC162 at 1×10(-4) mol/L inhibited the current density of I(Ca-L) from (8.98±0.40) pA/pF to (4.84±0.44) pA/pF (P<0.01, n=5) and inhibited that of I(to) from (18.69±2.42) pA/pF to (11.73±1.67) pA/pF (P<0.01, n=5). Furthermore, the effects of naltrindole, a highly selective antagonist of δ-opioid receptors, on I(Ca-L) and I(to) were also observed. The results showed that naltrindole alone had no effects on I(Ca-L) and I(to), while it abolished the inhibitory effects of SNC162 on I(Ca-L) and I(to). In conclusion, SNC162 concentration-dependently inhibited I(Ca-L) and I(to) in rat ventricular myocytes via activation of the δ-opioid receptors, which may be a fundamental mechanism underlying the antiarrhythmic effect of activating δ-opioid receptors.

Studies on chemical constituents in the seeds of Nigella glandulifera / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the chemical constituents in the seeds of Nigella glandulifera.</p><p><b>METHOD</b>The chemical constituents were isolated and repeatedly purified on silica gel column. They were identified and structurally elucidated by means of physio-chemical constants and spectral analysis.</p><p><b>RESULT</b>Nine compounds were identified as nigellamose (I), alpha-hederin (II), 3-O-[beta-D-xylopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinpyranosyl]-hederagenin (III), sucrose (IV), stearic acid (V), 1-O-hexadecanolenin (VI), beta-sitosterol (VII), daucosterol (VIII) and p-hydroxybenzoic acid (IX).</p><p><b>CONCLUSION</b>I, II, III, VI, VIII and IX were obtained from the plant for the first time, and I is a new compound.</p>

An outbreak of SARS in Dongcheng District, Beijing during March to June 2003 / 中国医学科学院学报

<p><b>OBJECTIVE</b>To describe epidemiological characteristics of an outbreak of severe acute respiratory syndrome (SRAS) in Dongcheng District, Beijing during March to June 2003.</p><p><b>METHODS</b>Data of SARS cases notified from Dongcheng District Center for Disease Control and Prevention (CDC) and supplemented by other channels were collected. All data were input into dataset files by Microsoft Excel-2000 software and analyzed with SPSS version 10.0 software.</p><p><b>RESULTS</b>Totally, 572 cases notified were collected during this period in Dongcheng District, Beijing, and 99 of them were excluded from SARS, because of diagnosis of common cold, pneumonia, measles, or rubella, etc. Actually, 473 SARS cases were analyzed. Attack rate of SARS in permanent residents of Dongcheng was 28.3 per 100,000. Forty-one of them died, with a case-fatality ratio of 8.7%. Outbreak of SARS in Dongcheng District started on March 14, with a peak during mid- and late April, and dropped from May 5, 2003. Persons were all susceptible to SARS, with the highest proportion at ages of 20-50 years, which accounted for 68.7% of the total cases. Average age of the patients at their onset was 40.7 years. No gender difference in SARS cases was found. Number of SARS cases in health care workers (HCWs) accounted for 18.0% and that in the retired persons accounted for 15.4% of the total cases. Cases occurred in all 10 sub-districts of Dongcheng. Totally, 230 of the 572 notified cases (40.2%) hospitalized at local hospitals under the jurisdiction of Dongcheng District. Eighteen of 85 cases of SARS occurred in health care workers of local hospitals, accounting for 4.5% of the total number of health care workers working at the wards caring for SARS patients or at fever clinics. There were 34.7% of SARS cases without any contact histories before their onset. Familial aggregation phenomena were observed in 41.8% of the cases and 18.1% of households. And, 7.4% (attack rate) in those exposed to SARS cases suffered the illness during the periods of quarantine.</p><p><b>CONCLUSIONS</b>SARS appeared outbreak in Dongcheng District, Beijing during March to June 2003. People were all susceptible to SARS, which mainly threatened the young adults and the middle-aged, as well as health care workers and the retired workers. Main mode of transmission was exposure to SARS patients in a near distance at hospitals or families. Prevention and control of SARS should be focused on early isolation of patients and quarantine for the contacts. Current available measures to prevent and control SARS proved effective.</p>