Research Progress of Adverse Events Related to PD-1/PD-L1 Inhibitors Based Combination Therapy / 中国肺癌杂志

The development of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of cancer patients, but a large population of patients are still ineffective to ICIs treatment or develop aquired drug resistance. In order to improve the clinical benefits, a number of studies on ICIs based combination therapy have been actively explored, and have achieved satisfactory results. With the application of ICIs based combination therapy in clinical practice, increasing attention has been paid to the safety of combination therapy and the management of treatment-related adverse events. In this review, the characteristics of adverse events related to ICIs based combination therapies, especially programmed cell death protein 1/protein ligand 1 (PD-1/PD-L1) inhibitors are discussed, in order to provide profound thoughts for toxicity evaluation and individualized treatment decision in future clinical practice.
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Growth factors promote the therapeutical effects of autologous bone marrow mesenchymal stem cell transplantation on acute myocardial infarction / 中国组织工程研究

BACKGROUND:The growth factor is a potent mobilization agent for stem cels, which can increase adhesion and proliferation of injected cels, induce stem cels to migrate to the infarct zone, proliferate, differentiate, as wel as participate in myocardiac repair. OBJECTIVE: To investigate the effect of hepatocyte growth factor (HGF) and insulin-like growth factor (IGF) on transplantation of bone marrow mesenchymal stem cels (BMSCs) after acute myocardial infarction. METHODS: Primary rabbit BMSCs were culturedin vitro and labeled by red fluorescence dye CM-Dil for transplantation. After the mid third of left anterior descending was ligated, model rabbits were grouped into four groups: control group, BMSCs group, HGF+IGF group, and HGF+IGF+BMSCs group (n=6 in each group). Different interventional agents were injected into the myocardium at four sites within the ischemic region. Masson trichrome staining was performed to determine viable myocardium, and immunofluorescence staining was used to identify BMSCs differentiation. The cardiac function was assessed with Doppler echocardiography. RESULTS AND CONCLUSION:Four weeks after treatment, CM-Dil/cTNT+ cels significantly increased in the HGF+IGF+BMSCs group, compared with BMSCs group. Consequently, viable myocardial tissues significantly increased, left ventricular ejection fraction was significantly improved, and left ventricular end-diatolic volume significantly decreased in the HGF+IGF+BMSCs group, relative to the other three groups. Combination of HGF and IGF that promotes differentiation of transplanted autologous BMSCs into cardiomyocytes, thus increasing viable myocardium, improving left ventricular function, and inhibiting left ventricular remodeling, may be a new method for the celltreatment of acute myocardial infarction.

Two-way concentration-dependent effect of H2O2 on I(Kur) and I(Ca,L) in human atrial myocytes / 生理学报

It has been shown that oxidative stress correlates with atrial fibrillation (AF). The purpose of the present study was to investigate the effects of reactive oxygen species (ROS) on the electrophysiological activity of human atrial myocytes. Right atrial appendages were obtained from patients with AF (AF group, n=12) and without AF (non-AF group, n=12). Single human atrial myocytes were isolated through enzymatic dissociation with type XXIV protease and type V collagenase, then divided into three subgroups: control group (n=12), H2O2 group (0.1, 0.2, 0.5, 0.75, 1, 2, 5, 10 mumol/L, n=7 at each concentration) and vitamin C (antioxidant) group (1 mumol/L, n=7). Ultrarapid delayed rectifier K(+) current (I(Kur)), L-type calcium current (I(Ca,L)) and action potential duration (APD) were recorded by whole-cell patch clamp. In AF control group, the maximum current densities of I(Kur) and I(Ca,L) were significantly lower than that in non-AF control group (both P<0.05) and APD(90) was significantly shorter as well (P<0.05). In both non-AF and AF groups, H2O2 showed two-way concentration-dependent effect on I(Kur) and I(Ca,L). The maximum current densities of I(Kur) and I(Ca,L) was significantly increased at lower H2O2 concentration, but was decreased at higher H2O2 concentration. In non-AF group, 0.2 mumol/L H2O2 caused a peak increase in the maximum current identities of I(Kur) [(8.92+/-0.51) pA/pF, P<0.05] and I(Ca,L) [(9.32+/-0.67) pA/pF, P<0.05]. H2O2 at a concentration higher than 0.75 mumol/L decreased I(Kur) and I(Ca,L). When the H2O2 concentrations were 0.2, 1, 2, 5 and 10 mumol/L, APD(90) was significantly shorter compared with that in non-AF control group (P<0.05), meanwhile it had no significant difference from that in AF control group. In AF group, the peak effective concentration of H2O2 was 0.5 mumol/L, and the turning concentration was 1 mumol/L. The H2O2 concentration-current density curve in AF group was similar to that in non-AF group, but the turning point shifted to the right, indicating that the way that H2O2 acted on ion channels in AF was the same as that in non-AF, however, the sensitivity of ion channels to H2O2 was decreased in AF. Vitamin C reversed these changes induced by H2O2, and did not affect the characteristics of ion channels. H2O2-induced electrophysiological changes in human atrial myocytes were similar to atrial electrical remodeling (AER) in AF, suggesting that ROS might induce AF. Meanwhile, H2O2 also could aggravate AER in AF, contributing to the maintenance of AF. The results suggest that antioxidants might play a significant role in the prevention and treatment of AF.

Genetic damages in somatic and germ cells from patients of benzene poisoning, asbestosis and gas poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To compare the extent of genetic damages in somatic and germ cells from patients of benzene poisoning, silicosis and gas poisoning, which may provide clues for protection and reproductive healthcare.</p><p><b>METHODS</b>174 patients with three types of occupational disease (including 48 with benzene poisoning, 71 with silicosis and 55 with gas poisoning) and 80 healthy controls had their aberrant chromosome and micronuclei rates measured with routine methods. Male patients also had their sperm samples measured for sperm abnormities and de novo mutations.</p><p><b>RESULTS</b>The aberrant chromosome rate, micro-nuclei rate and sperm abnormity were as followed: benzene poisoning 0.4%, 1.52 per thousand, (62 +/- 14%), silicosis 0.51%, 2.31 per thousand, (41 +/- 7%), harmful gas poisoning 0.42%, 1.55 per thousand, (48 +/- 8%), all being significantly higher than those of the controls [0.20%, 0.34 per thousand, (27 +/- 5)%]. The aberrant chromosome and micro-nuclei rates of silicosis group were higher than other two groups, but without statistical significance. Sperm abnormity of benzene poisoning group was significantly higher than that of other groups. In addition, de novo mutations in sperm of benzene poisoning group were detected.</p><p><b>CONCLUSION</b>Patients with the studied occupational diseases not only have genetic damage in their somatic cells, but also acquire de novo mutations in germ cells.</p>

Palindromic sequence-mediated de novo chromosome translocation in sperm samples derived from normal and oligospermic males / 中华男科学杂志

<p><b>OBJECTIVE</b>To systematically explore the occurrence of a novel type of chromosome translocation in human sperm samples.</p><p><b>METHODS</b>Specific translocation junction fragments were quantified using nested and/or multi-nested PCR in sperm DNA derived from 28 oligospermic patients and 32 normal controls.</p><p><b>RESULTS</b>t(11;22) was detected in 49 samples. At least 4 samples were found to have t(1;22) (p21.2;q11.2), t(17;22) (q11;q11) or t(X;22) (q27;q11). The mutation rate seemed to be associated not with age or semen volume, but with sperm concentration (r = -0.389, P < 0.05) and motility (r = -0.397, P < 0.05). Correlation was not found between homology of palindromic sequences and mutation rate.</p><p><b>CONCLUSION</b>Palindromic sequence mediated chromosome translocation is common in human sperm, and associated with sperm concentration and motility. Measurement of such mutations may provide a molecular-level reference for assessing sperm quality.</p>