Progress for targeting adenosine A2A receptors in cancer immunotherapy / 药学学报

Immunotherapy has completely changed the paradigm of clinical tumor treatment, but immune checkpoint inhibitors still have low objective response rates and are prone to drug resistance for most solid tumors. The immune suppression tumor microenvironment and complicated tumor immune escape mechanisms are key factors that affect the clinical outcome and response rates. Therefore, it is critical to reverse the obstacle of the tumor microenvironment to improve immunotherapy efficacy. The immune suppression caused by the increased level of adenosine in the tumor microenvironment raises the attention of people. Targeting adenosine receptors, especially A2AR, will be an effective strategy to improve immunotherapy efficacy. Targeting the adenosine-A2A pathway can increase immune infiltration, enhance immune cell function, and partially reverse immunotherapy-insensitive "cold tumors" to "hot tumors" to enhance treatment response rates and improve the efficacy of current immunotherapy. At present, many adenosine receptor inhibitors have shown good results in clinical trials, especially in combination with immune checkpoint inhibitors, chemotherapy, and adoptive cell transfer therapeutic drugs, which are expected to be used for tumor immunotherapy to bring new breakthroughs. This article reviews the accumulation mode of adenosine in the tumor microenvironment, the role of A2AR and their regulatory mechanism in immune response, the progress of A2AR inhibitors in clinical trials, potential risks to target A2AR, and the prospects for therapeutic targeting A2AR.

Experimental study of proteasome inhibitor MG132 up-regulates Wnt/β-catenin signaling pathway to improve osteoporosis / 中国骨伤

OBJECTIVE@#To explore the mechanism of proteasome inhibitor MG132 in improving osteoporosis.@*METHODS@#Total of 32 female SD rats, weighing 220 to 250 g and 8 weeks old, were selected. They were randomly divided into 4 groups(n=8). Rats of group A and group B were cut off ovaris on both sides to make model of osteoporosis, and then they were given proteasome inhibitors MG132 and dimethyl sufoxide (DMSO) respectively. Group C was a sham group and rats were given MG132. Group D was a normal group and rats were given MG132 too. The rats were killed in batches at 6 and 12 weeks after administration, and the femoral neck tissues were obtained. Relevant data were analyzed, such as pathomorphological observation, micro-CT analysis, detection of 20S proteasome activity in tissues, and expression of Wnt and β-catenin.@*RESULTS@#Morphological observation showed that the trabecular were slightly thinner, reticulated, and occasionally interrupted in group A, while the trabecular were obviously thinner and discontinuous in group B. And the trabecular were intact and arranged reticulated in group C and D. The analysis results of bone mineral density(BMD), bone surface(BS), bone volume/total volume(BV/TV) and trabecular thickness(Tb.Th) showed that group B was worse than other groups in all parameters at different time points(P<0.05), and group A was worse than group C and group D in BS(P<0.05), there was no significant difference in all parameters between group C and group D. RFU value of 20S proteasome in group B was significantly higher than that in other groups(P<0.05). According to the results of Western blot, the gray values of Wnt protein and β-catenin protein in group A were significantly higher than those in other groups (P<0.05).@*CONCLUSION@#MG-132, a ubiquitin proteasome inhibitor, can regulate Wnt/β-catenin signaling pathway by inhibiting the degradation of β-catenin protein, and delaying the occurrence and development of osteoporosis.

Effect of Bushen Shugan Prescription on Oxidative Stress and TGF-β1/Smad Signaling Pathway in Hippocampus of Senile Depressed Mice / 中国实验方剂学杂志

Objective:To observe the changes in oxidative stress and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）/Smad signaling pathway in hippocampal tissue of senile depressed mice after chronic unpredictable mild stress and to explore the possible anti-depression mechanism of Bushen Shugan prescription. Method:Ninety five-month-old mice were randomly divided into six groups， namely the normal group， senile depression model group， high-， medium-， and low-dose Bushen Shugan prescription groups， and fluoxetine group， with 15 in each group. Mice in all groups， except for the normal group， were exposed to chronic unpredictable mild stress （CUMS） for inducing the senile depression. Since the first day of modeling， the mice in the high-， medium- and low-dose Bushen Shugan prescription groups were gavaged with 19.5， 9.75， 4.87 g·kg^-1 Bushen Shugan prescription， the ones in the fluoxetine group with 0.033 g·kg^-1fluoxetine， and those in the normal and senile depression model groups with an equal volume of normal saline for 21 successive days. The behavioral responses of mice in each group were evaluated in the open field test （OFT）， and the hippocampal tissues of mice were collected for testing the relevant indexes. The superoxide dismutase （SOD） content was determined by WST-1 method， malondialdehyde （MDA） content by TBA method， glutathione （GSH） content by micro enzyme-linked immunosorbent assay （ELISA）， and mRNA expression of TGF-<italic>β</italic>₁， Smad2， Smad3， and Smad7 by Real-time polymerase chain reaction （Real-time PCR）. Result:Compared with the normal group， the senile depression model group exhibited significantly lowered horizontal and vertical scores in OFT， decreased SOD and GSH contents in hippocampal tissues， elevated MDA （<italic>P</italic><0.05）， up-regulated TGF-<italic>β</italic>₁， Smad2， and Smad3 mRNA expression， and down-regulated Smad7 （<italic>P</italic><0.05）. Compared with the senile depression model group， Bushen Shugan prescription at the high， medium， and low doses and fluoxetine all increased SOD and GSH contents in mouse hippocampal tissues， decreased the MDA content （<italic>P</italic><0.05）， down-regulated the mRNA expression of TGF-<italic>β</italic>₁， Smad2， and Smad3 in hippocampal tissues， and up-regulated the Smad7 mRNA expression （<italic>P</italic><0.05）. The comparison with the high-dose Bushen Shugan prescription group showed that the SOD and GSH contents in hippocampal tissues of mice in the medium- and low-dose Bushen Shugan prescription groups declined significantly， while the MDA contents rose significantly （<italic>P</italic><0.05）. Besides， the mRNA expression levels of TGF-<italic>β</italic>₁， Smad2 and Smad3 in the hippocampal tissues of mice in the medium- and low-dose Bushen Shugan prescription groups were significantly up-regulated， and those of Smad7 were significantly down-regulated （<italic>P</italic><0.05）. Conclusion:Bushen Shugan prescription alleviates the depression symptoms in aged SAPM8 mice possibly by regulating the hippocampal oxidative stress and TGF-<italic>β</italic>₁/Smad signaling pathway.

Clinical effects of suture anchor with V-Y tenoplasty in treating old Achilles tendon rupture / 中国骨伤

OBJECTIVE@#To explore clinical effects of suture anchor with V-Y tenoplasty for the treatment of old Achilles tendon rupture.@*METHODS@#From May 2014 to March 2018, 26 patients with old Achilles tendon rupture treated by suture anchor with V-Y tenoplasty, including 18 males and 8 females aged from 19 to 56 years old with an average of (36.0±11.7) years old, the courses of disease ranged from 42 to 62 days with an average of (49.0±5.3) days; the distances of Achilles tendon-shortening ranged from 2 to 7 cm with an average of (4.0±1.6) cm. Postoperative complications were observed, preoperative and postoperative American Orthopaedic Foot and Ankle Soviety(AOFAS) score were used to evaluate clinical effects.@*RESULTS@#All patients were followed up from 8 to 18 months with an average of(12.0±2.5) months. No Achilles tendon rupture occurred again. Postoperative AOFAS score at 3 months(93.37 ±3.48) was higher than before operation(57.26±5.06)(t=9.564, <0.05), and 14 patients got excellent results, 11 moderate and 1 poor.@*CONCLUSIONS@#Suture anchor with V-Y tenoplasty for old Achilles tendon rupture could achieve stable fixation, relieve pain, improve walking ability and quality of life, and also recover good function of ankle joint.

A comparative study between on-endcaps and non-endcaps titanium mesh cage for the treatment of elderly cervical spondylotic myelopathy complicated with osteoporosis approach for anterior cervical spine surgery / 中国骨伤

<p><b>OBJECTIVE</b>To compare radiographic results and clinical effects of titanium mesh cage with two endcaps(on-endcaps titanium mesh cage) and without endcaps(non-endcaps titanium mesh cage) in anterior cervical corpectomy and fusion(ACCF) for elderly cervical spondylotic myelopathy.</p><p><b>METHODS</b>The clinical data of 60 patients with cervical spondylotic myelopathy underwent ACCF from January 2011 to January 2016 were retrospectively analyzed. There were 26 males and 34 females, aged from 68 to 79 years old with a mean 75.8 years old. The patients were divided into two groups according to the different titanium mesh cage, using on-endcaps titanium mesh cage(group A, 32 cases) or non-endcaps titanium mesh cage (group B, 28 cases). The nerve function was evaluated by JOA score system; the height of intervertebral fusion segments and fusion segmental lordosis angle (Cobb angle) were measured by cervical lateral X-ray films, the bone graft fusion rate of titanium mesh was evaluated by CT.</p><p><b>RESULTS</b>All the patients were followed up from 1 to 2 years with an average of 1.5 years. The preoperative JOA scores of group A were 9.3±1.7, postoperative at 1 week, 3 months, 1 year were 14.2±1.8, 15.7±1.2, 15.4±1.5, respectively; and the preoperative JOA scores of group B were 9.1±1.8, postoperative at 1 week, 3 months, 1 year were 14.5±1.3, 14.9±1.7, 15.2±1.6, respectively. The postoperative JOA scores between two groups were obviously improved than that of preoperative (<0.05). There was no significant difference in JOA scores of 3 time-point after operation between two groups (>0.05). In the group A, preoperative intervertebral height were(42.1±2.4) mm, postoperative at 1 week, 3 months, 1 year were (45.3±3.2) mm, (44.7±2.9) mm, (44.5±3.0) mm, respectively; preoperative Cobb angle of fusion segments were (5.3±1.2)°, postoperative at 1 week, 3 months, 1 year were (10.3±1.9) °, (10.1±1.7) °, (9.9±1.3) °, respectively. And in group B, preoperative intervertebral height were (43.4±2.3)mm, postoperative at 1 week, 3 months, 1 year were (45.7±2.8) mm, (44.2±2.7) mm, (41.5±2.1) mm, respectively; preoperative Cobb angle of fusion segments were (5.4±1.0) °, postoperative at 1 week, 3 months, 1 year were (11.2±1.8)°, (10.8±1.6)°, (7.2±1.4) °, respectively. The postoperative intervertebral height, Cobb angle of fusion segments between two groups were obviously improved than that of preoperative (<0.05). There was no significant difference in intervertebral height and Cobb angle at 1 week, 3 months after operation between two groups(>0.05). One year after operation, intervertebral height and Cobb angle in group A was better than that of group B(<0.05).</p><p><b>CONCLUSIONS</b>On-endcaps titanium mesh cage is superior to non-endcaps titanium mesh cage in the maintenance of cervical intervebral height and segmental lordosis angle postoperatively at elderly spondylotic myelopathy complicated with osteoporosis. The usage of on-endcaps titanium mesh cage can effectively reduce postoperative subsidence rate.</p>

Unilateral pedicle screw fixation and transforaminal lumbar interbody fusion through paraspinal muscle approach for recurrent lumbar disc herniation combined with lumbar instability / 中国骨伤

<p><b>OBJECTIVE</b>To explore the clinical effects of unilateral pedicle screw fixation and transforaminal lumbar interbody fusion (TLIF) through paraspinal muscle approach for recurrent lumbar disc herniation combined with lumbar instability.</p><p><b>METHODS</b>A total of 35 patients with recurrent lumbar disc herniation combined with lumbar instability were treated between March 2008 and May 2010, including 15 patients managed by the paraspinal muscle approach with unilateral pedicle screw fixation and transforaminal lumbar interbody fusion (TLIF) (unilateral fixation group) and 20 patients by the posterior midline approach with bilateral pedicle screw fixation and posterior lumbar interbody fusion (bilateral fixation group). Operation time and intraoperative blood loss were observed, preoperative and postoperative JOA score and VAS score in low back pain and legs pain, the interbody fusion condition were compared between two groups.</p><p><b>RESULTS</b>All patients were followed up from 6 to 30 months with an average 16.8 months. All clinical symptoms had obviously improved postoperatively. X-rays showed good interbody fusion (only 1 case did not obtain fusion in bilateral fixation group) without cage displacement or settlement and implant loosening or breakage. There was significant difference in operation time and the intraoperative blood loss between two groups (P < 0.05). Postoperative JOA score had obviously decreased than preoperative one (P < 0.05). At 1 week after surgery, there was significant difference in VAS score of low back pain between two groups and there was no significant difference in VAS score of legs pain between two groups (P > 0.05); at final follow-up, there was no significant difference in VAS score of low back pain and legs pain between two groups (P > 0.05).</p><p><b>CONCLUSION</b>Two methods both can obtain satisfactory effect in treating recurrent lumbar disc herniation combined with lumbar instability. Through the paraspinal muscle approach with unilateral pedicle screw fixation and TLIF has advantages of smaller surgical incision, shorter operation time, less intraoperative blood loss, faster relief in low back pain after operation, etc.</p>

Clinical analysis of an interspinous stabilization system (wallis) in treating lumbar degenerative disease / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate clinical results of an interspinous stabilization system (Wallis) in treating lumbar degenerative disease in the short-term.</p><p><b>METHODS</b>From August 2007 to June 2010,48 patients with lumbar degenerative disease who were treated with interspinous stabilization system, the data of patients were analyzed retrospectively. In all of the 48 cases, there were 30 males and 18 females with an average age of 54.2 years (ranged, 40 to 68 years). Forty-four cases were with single segment and 4 cases with two segments. Of them, 4 cases were in L3, 4, 40 cases were in L4, 5, 4 cases were in L3, 4 and L4, 5. The radiographic data of patients were analyzed. Clinical effects were evaluated by Japanese Orthopedic Association (JOA) score system and low back pain disability questionnaire (Oswestry) and Odom method.</p><p><b>RESULTS</b>All the patients were followed up from 1 to 2 years with an average of 18 months. According to Odom's criteria, 20 cases obtained excellent results, 24 good, 4 fair. JOA score increased from 12.4 +/- 2.7 preoperatively to 26.1 +/- 2.0 postoperatively (P < 0.01). Oswestry score decreased from 14.1 +/- 2.9 preoperatively to 5.5 +/- 1.8 postoperatively (P < 0.01). The posterior height of intervertebral space and height of nerve root canal increased compared with that of preperative height.</p><p><b>CONCLUSION</b>The treatment of lumbar degenerative disease with interspinous stabilization system can obtain satisfactory effects in the near future. It can retain dynamic stable of corresponding segments, expand volume of vertebral canal, and is safe and feasible.</p>

On the in vitro diagnostic medical equipment industry standard YY 0648-2008 / 中国医疗器械杂志

The paper introduces the scope of application of standard and basic contents of YY0648-2008. It shows part of the standard terms of understanding, especially in the original use of the GB 4793.1-2007 standard provisions based on new knowledge and understanding.