Research advances in new technologies in targeted protein degradation / 药学学报

In recent years, the targeted protein degradation technology has developed quickly, with proteolysis-targeting chimera (PROTAC) as the best-known strategy through exploring the ubiquitin-proteasome system. A number of new targeted protein degradation strategies have been emerging to expand the scope of protein degradation technology, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs) and chimeras based on chaperone-mediated autophagy (CMA). The emerging methodologies have explored another important protein degradation system in eukaryotes-lysosomal systems, such as the endosome-lysosome pathway and the autophagy-lysosome pathway. This review summaries the mechanisms and features of different strategies for targeted protein degradation, with a special emphasis on the new targeted protein degradation technologies, such as their current status, advantages and limitations.

Chemical constituents from Xanthii Fructus / 中国中药杂志

This study was carried out to investigate the chemical constituents from Xanthii Fructus(the fruits of Xanthium sibiricum). The compounds were separated and purified by silica gel column chromatography, Sephadex LH-20 and ODS chromatography and semi-preparative HPLC. Base on HR-ESI-MS, NMR and other spectral data, their structures were identified. The anti-inflammatory activity of the isolated compounds was evaluated by lipopolysaccharide(LPS)-induced macrophage RAW264.7 as a screening model. A total of twenty-one compounds were isolated from the EtOAc fraction of 95% ethanol extract and identified as uracil(1), thymine(2), uridine(3), indole-3-carbaldehyde(4), indole-3-carboxylic acid(5), 2'-O-methyluridine(6), guanosine(7), 2,4(1H,3H)-quinazolinedione(8), 3-hydroxy-3-(2-hydroxyethyl)indolin-2-one(9), nicotinamide(10), N-acetyl-L-phenylalaninol(11), heliolactam(12), terresoxazine(13), caudatin(14), qingyangshengenin(15), caudatin-3-O-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside(16), caudatin-3-O-β-D-cymaropyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside(17), caudatin-3-O-α-L-cymaropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-α-L-cymaropyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranoside(18), qinyangshengenin-3-O-β-D-oleandropyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranoside(19), qinyangshengenin-3-O-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-digitoxopyranoside(20), rostratamine-3-O-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside(21). Compounds 5-21 are obtained from genus Xanthium for the first time. Compounds 12 and 13 indirectly exhibited anti-inflammatory activity by suppressing LPS-induced NO production in RAW264.7 cells with IC_(50) values of(15.45±0.56) and(20.14±0.78) μmol·L~(-1), respectively.

Application of three-dimensional printing technology to design individual angle section on Chevron of hallux valgus osteotomy / 中国骨伤

<p><b>OBJECTIVE</b>To explore clinical application of three-dimensional printing technology to design individual angle section on Chevron of hallux valgus osteotomy.</p><p><b>METHODS</b>From May 2013 to May 2016, 47 patients(66 feet) with mild to moderate hallux valgus treated by Chevron osteotomy according to different preoperative design were divided into computer osteotomy group(group A) and traditional osteotomy group(group B). In group A, there were 25 patients (33 feet), including 4 males(5 feet) and 21 females(28 feet) with an average age of (47.88±6.08) years old, average weight IMA was (13.58±1.15) degree, AOFAS score was 59.00±5.86, and treated individual 3D printing technology to design operation scheme. While in group B, there were 22 patients (33 feet), including 3 males (3 feet) and 19 females (28 feet) with an average age of (48.16±6.16) years old, average weight IMA was(13.51±1.14) degree, AOFAS score was 60.67±5.85, and treated with osteotomy according to surgical experience. Operation time, blood loss, hospital stays, VAS score at 1 week after operation, wound healing and improvement of postoperative weight-bearing intermetatarsal angle(IMA) were compared between two groups, AOFAS score system was used to evaluate ankle function after surgery.</p><p><b>RESULTS</b>There was no significant difference in following-up between group A 12.41±2.32 and group B 11.73±2.76. There was 1 patient in group B were excluded. Others perform good wounds healing on the first stage after operation. There were no significant differences in operation time, blood loss, hospital stays and VAS score at 1 week after operation(<0.05); IMA in group A was (5.21±0.88)°, (6.42±0.85)° in group B, and had significant differences between two groups (=5.68, <0.05). There was obvious meaning in AOFAS score between group A 88.15±5.19 and group B 82.90±5.01(=4.14, <0.05). Fourteen feet in group A obtained excellent results and 19 feet good, while 5 feet in group B obtained excellent results and 27 feet good.</p><p><b>CONCLUSIONS</b>Compared with traditional osteotomy group, three-dimensional printing technology to design individual angle section on Chevron of hallux valgus osteotomy could better correct IMA, improve postoperative foot function, and it is a kind of individualized and digital method to design operation.</p>

Trauma care construction under the guidance of county-level trauma centers / 中华创伤杂志(英文版)

Severe trauma has the characteristics of complicated condition, multiple organs involved, limited auxiliary examinations, and difficulty in treatment. Most of the trauma patients were sent to primary hospitals to receive treatments. But the traditional mode of separate discipline management can easily lead to delayed treatment, missed or wrong diagnosis and high disability, which causes a high mortality in severe trauma patients. Therefore, if the primary hospitals, especially county-level hospitals (usually the top general hospital within the administrative region of a county), can establish a scientific and comprehensive trauma care system, the success rate of trauma rescue in this region can be greatly improved. On March 1st, 2013, Tiantai People's Hospital of Zhejiang Province, China set up a trauma care center, which integrated the pre-hospital and in-hospital trauma treatment procedures, and has achieved good economic and social benefits. Till March 1st, 2017, 1265 severe trauma patients (injury severity score >16) have been treated in this trauma center. The rescue success rate reached 95% and the delayed and/or missed diagnosis rate was less than 5%. Totally 86 severe cases of pelvic fractures with unstable hemodynamics were treated, and the success rate was 92%. The in-hospital emergency rescue response time is less than 3 min, and the time from definite diagnosis to surgery is within 35 min.

Choices of the internal fixation and approaches on unstable pelvic ring fractures / 中国骨伤

<p><b>OBJECTIVE</b>To discuss the suitable surgical approach and the internal fixation of unstable pelvic pelvic fractures.</p><p><b>METHODS</b>From May 2010 to May 2015, 45 patients with unstable pelvic fractures were treated with different approaches and fixations, including 38 males and 7 females with an average age of 45 years ranging from 21 to 61 years. The course was within 2 weeks. According to Young-Burg classification, 23 patients were lateral compression injuries, 6 patients were vertical shearing injuries, 16 patients were anterior-posterior compression injuries. All patients had hip pain and limitation of motion, the X-rays showed the pelvic ring fracture.</p><p><b>RESULTS</b>All wounds healed well without complications, 45 cases were followed up for a mean period of 13 months (ranged 9 to 21 months). Patients with hip pain had a good postoperative pain relief. The post-operative X-rays showed the reduction was satisfied and the pelvic ring shaped well. According to Majeed standards, the final follow-up score was 93.5±11.6, 35 cases got excellent results, 8 were good, 2 were fare.</p><p><b>CONCLUSIONS</b>The unstable pelvic and acetabular fractures are always with compound injury. Beside the reduction, to decrease the second surgery trauma should take into consideration as well, the intra-articular reduction and the stability of the pelvic were especially valued, so combined the different approach with minimal invasive technique can get good clinical result.</p>

Surgical treatment and construction for traumatic floating shoulder / 中国骨伤

<p><b>OBJECTIVE</b>To explore surgical therapeutic strategies and clinical effects for floating shoulder injury.</p><p><b>METHODS</b>From March 2010 to December 2013, 12 patients with floating shoulder injury were treated by open reduction and plate screw fixation,including 10 males and 2 females aged from 22 to 45 years old with an average of 31.7 years old. Preoperative X-ray and CT showed 11 cases were ipsilateral clavicle fracture with scapular neck fractures, 1 case was scapular neck fracture with ipsilateral acromioclavicular dislocation. Postoperative complications were observed and Herscvici functional scoring were used to evaluate clinical effects.</p><p><b>RESULTS</b>Twelve patients were followed up from 8 to 26 months (averaged 15 months). All patients obtained bone union, and no inflammation, loosening and breakage of plate and screw were found. According to Herscvici scoring, 9 cases got excellent results, 2 good and 1 moderate.</p><p><b>CONCLUSION</b>Reconstruction of anatomical structure and stability of floating shoulder joint injury could shorten time of shoulder joint brake and fixation, then got excellent clinical outcomes.</p>

Surgical treatment of multiple ligament injuries of knee joints / 中国骨伤

<p><b>OBJECTIVE</b>To study operative effects for the treatment of multiple ligament injuries of knee joints.</p><p><b>METHODS</b>From 2008 to 2013, 26 patients (17 males and 9 females) with multiple ligament injuries of knee joints were treated surgically. The average age was 40.7 years old, ranging from 29 to 55 years old. All the patients were treated with arthroscopic reconstruction of cruiate ligament with autogenous or allogeneic hamstrings and tendon, and at the same time received repair of medial collateral ligament and lateral collateral ligament, as well as the treatment of exterior and interior complex injuries. Nine patients received second stage operation after the initial operation for mistake or missed diagnosis, and other patients were treated at the first stage. The Lysholm scoring system was used to evaluate function and stability of knee joints before and after operation.</p><p><b>RESULTS</b>All the patients were followed up for an average duration of 1.6 years (ranged, 0.8 to 3.2 years). The mean awaiting time for operation was 1.2 months. The Lysholm score was improved from preoperative 42.5 +/- 4.5 (ranged, 33 to 48) to the latest follow-up 78.1 +/- 3.9 (ranged, 57 to 95). The function of knee joint was improved obviously in the arthroscopic reconstruction patients, with joint range of motion exceeding 900 and with Varus & Valgus tests near to normal. All the patients had negative findings in the Lachman test at 70 degrees of flexion.</p><p><b>CONCLUSION</b>Arthroscopic reconstruction should be the first choice in treating multiple ligament injuries of knee joints. If the anterior and posterior cruciate ligament injuries can't be treated simultaneously, the posterior cruciate ligament injuries should be treated preferentially at the first stage and the anterior cruciate ligament injuries should be treated at the second stage. The diagnosis of posterior cruciate ligament is easy to be missed.</p>

Curative effect analysis of surgical treatment of Lisfranc joint injuries / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical results and influence factors in surgical treatment of the Lisfranc joint injury.</p><p><b>METHODS</b>From Jan. 2009 to Nov. 2011 ,13 patients (14 feet) with Lisfranc joiat injury received open reduction and screw or wire or external fixation including 9 males and 4 females with an average age of 42 years old ranging from 18 to 61 years. According to the Myerson classification,there were 1 case of type A, 9 of type B and 4 of type C. All the patients received open reduction and internal (1 with external) fixation with screw or Kirschner wire within 22 days after injury. The postoperative function was estimated by mid-foot scoring scale of AOFAS. X-ray were used in radiography estimation.</p><p><b>RESULTS</b>All the patients were followed up for 5 to 30 months (averaged 20 months). According to mid-foot scoring scale of AOFAS,there were 8 feet with excellent results,4 with good and 2 with fair results. The anatomical reduction was observed in 12 feet and all the patients obtained bony union according to the results of X-ray.</p><p><b>CONCLUSION</b>Open reduction and internal fixation is a good choice for the treatment of Lisfranc joint injury. A preoperative estimate,proper reduction during operation and maintainence after operation may influence the clinical results.</p>

Choice of operative approaches for complex fractures of the quadrilateral area of acetabular / 中国骨伤

<p><b>OBJECTIVE</b>To compare different surgical approaches in order to obtain better surgical exposure and more reliable reset fixation according to the different types of quadrilateral area fractures of acetabular.</p><p><b>METHODS</b>From January 2006 to January 2011, 58 patients with the quadrilateral area fractures of acetabular were treated by surgical operation through the simple Kocher-Langenbeck (KL) approach, ilioinguinal approach, modified Stoppa approach, or combined surgical approach, or a combination of anterior column screw fixation percutaneously and modify Stoppa approach.</p><p><b>RESULTS</b>Forty-nine patients were followed up for an average time of 32 months ranging from 2 to 6 years. One patient with deep infection cured after treatment of effective antibiotics and drainage, 2 patients had a sciatic nerve injury, 2 cases of avascular necrosis of the femoral head. Among them, 36 cases were anatomical reducted, 8 were good and 5 were poor according to Matta's radiographic assessment system. According to the mean Merle d'Aubigne and Postel Score,32 patients got excellent result, 12 good,4 fair and 1 bad,the average score was (15.3 +/- 2.5).</p><p><b>CONCLUSION</b>Single classic surgical approach can only use for some types of the complex quadrilateral area fractures of acetabular while combination approach may need for some fractures. Modified Stoppa approach combined with ilioinguinal approach or a combination of anterior column acetabular screw fixation are the most effective surgical approaches for complex quadrilateral area fractures of acetabular.</p>

Analysis of 12 death cases of medical tangles after trauma / 法医学杂志

OBJECTIVE@#To explore the main problems and ideas in the death cases of medical tangles after trauma.@*METHODS@#Twelve death cases of medical tangles after trauma were selected from a forensic science institute during recent six years. Traumatic conditions, medical malpractices and contribute degree of malpractice were estimated and analyzed.@*RESULTS@#The reasons of trauma included accidents and intentional injury. Among these cases, there were 10 involved in malpractice, of which 7 cases played secondary role.@*CONCLUSION@#Diagnosis, symptom observation and emergency therapy are the important keys for determining the responsibility in death cases of medical tangles after trauma.

Clinical study on fludarabine combined with cytarabine regimen in the treatment of patients with refractory and relapsed acute myeloid leukemia / 中国实验血液学杂志

The aim of study was to evaluate the clinical efficacy and toxicity of fludarabine combined with cytarabine (FA) regimen in the treatment of patients with refractory and/or relapsed acute myeloid leukemia (AML). Nineteen cases with refractory/relapsed AML were treated with FA regimen in which fludarabine phosphate 25 mg/(m(2) x d), d1-5; cytarabine (Ara-C) 2 g/(m(2) x d), d1-5. Another 20 cases were treated with salvage chemotherapy (MAE regimen: mitoxantrone, Ara-C and etoposide or DAE regimen: daunorubicin, Ara-C and etoposide). All patients received at least 2 cycles chemotherapy. The results showed that 9 patients (47%) in FA regimen group achieved complete remission (CR), 8 cases (42%) obtained partial remission (PR), the clinical efficacy was superior to that of the MAE or DAE regimens (p < 0.05). Major toxicity of FA regimen was myelosuppression. Grade IV hematologic toxicity occurred in all patients received FA regimen. Nonhematologic complications consisted of gastrointestinal side effects, mucositis, liver toxicity, which were mild to moderate and could be alleviated with supportive therapy. In conclusion, FA regimen is an effective regimen for treatment of refractory and relapsed AML.

Treatment of fractures of tibia intercondylar eminence under arthroscopy using suture anchors / 中国骨伤

<p><b>OBJECTIVE</b>To explore a new technique of reduction and internal fixation for tibia intercondylar eminence fractures under arthroscopy.</p><p><b>METHODS</b>From June 2004 to February 2006, 9 patients with fresh tibia intercondylar eminence fracture (type II in 4 cases and type III in 5 cases) were treated with reduction and internal fixation using suture anchors (Depuy Mitek) under arthroscopy. All the patients, subject to regular post-operation functional exercise, were followed up for 6 to 22 months. The results were evaluated in the aspects of fracture reduction healing, knee joint relaxation and ROM, and functional restoration of overall limbs.</p><p><b>RESULTS</b>In the nine patients, the tibia intercondylar eminence fractures healed without displacement and nonunion. No knee joint relaxation or extension-restriction was found. Lysholm score indicated 93.8 +/- 2.3 at the 6th postoperative months.</p><p><b>CONCLUSION</b>The reduction and internal fixation of tibia intercondylar eminence fractures under arthroscopy using suture anchors demonstrate a reliable and easy-to-use technique. Operation under arthroscopy helps diagnose and treat other complications inside knee joint, merely resulting in slight injury. In addition,early functional exercise contributes to rapid recovery of knee joint's functions.</p>

Case-clinical studies on three different intervertebral fusion with bone graft and internal fixation in the treatment of cervical spondylotic myelopathy / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of three different intervertebral fusion with bone graft and internal fixation in the treatment of cervical spondylotic myelopathy.</p><p><b>METHODS</b>In the retrospective study, 83 patients (38 males and 45 females, with an average age of 69 years) with cervical spondylotic myelopathy were divided into three groups. The patients in three groups were treated by autogenous iliac bone grafting (Robingson grafting) with anterior cervical plate-screw fixation, Pyramesh with anterior cervical plate-screw fixation and BAK fixation respectively. JOA scores and the bony fusion time were recorded and the results were evaluated by numeric computer system.</p><p><b>RESULTS</b>The JOA scores of all the patients were higher than those before surgery (t = 1.55, P < 0.05). There were no statistical difference of JOA scores in the three groups (F = 2.51, P > 0.05).</p><p><b>CONCLUSION</b>It is concluded that internal fixation of the three types is promising to the treatment of cervical spondlotic myelopathy. Robingson grafting with anterior cervical plate-screw fixation provides good stability and bony fusion. BAK is better technically required but there was height loss in clinic. Pyramesh with anterior cervical plate-screw fixation combines the merits of both two techniques above but the cost is higher.</p>