ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.

Normothermic machine perfusion (NMP) is currently a research hotspot of organ preservation in the field of transplantation. Its safety and effectiveness of organ preservation have been clinically validated especially for preserving marginal donor organs. Various unique advantages of NMP are offered for in vitro organ function assessments, maintenance and organ injury repairing. Within the field of organ medicine, precise clinical interventions based upon in vivo or in vitro researches are implemented through an in vitro organ support system. With an aid of extracorporeal organ support system, an independent extracorporeal circulation system could be established for single or multiple organs more efficiently and safely. And physiological supports and other interventions for target organs are performed. Organ gene editing therapy, organ cell therapy, organ chemotherapy, organolytic virus therapy and organ physiological support therapy are all disciplines of organ quarantine therapy. This emerging theory provides a novel treatment for clinical organ diseases. This review summarized the use of NMP technology based upon the concepts and applications of organ medicine. Also the applications of organ isolation and protection therapy were discussed for organ transplantation and other research fields.

Objective:To investigate the effectiveness, safety, and advantages of modified radical neck dissection by gasless unilateral axillary approach (GUA-MRND) in the surgical management of selected patients with papillary thyroid cancer.Methods:We retrospectively analyzed patients with papillary thyroid cancer who underwent GUA-MRND (endoscopic group, n=16) versus unilateral open modified radical neck dissection (MRND) (open group, n=32) during the period from Jan. 2019 to Jun. 2021, including the differences in surgical efficiency, complication rate, and incisional satisfaction.Results:Compared MRND with GUA-MRND, the patients were younger ( P<0.05) , operative time and postoperative drainage anterior ( P<0.01) were slightly inferior in the latter, but it had obvious advantages in cervical swallowing discomfort and incision satisfaction evaluation ( P<0.05) . There was no significant difference in the incidence of temporary recurrent laryngeal nerve injury, intraoperative and postoperative bleeding, hematoma, infection, lymphatic or chylous leakage and supraclavicular numbness after surgery ( P>0.05) . The number of dissected lymph nodes in area II in the GUA-MRND was lower ( P<0.05) , but it was significantly higher ( P<0.01) in area III. And the average regional cleaning efficiency in the GUA-MRND was level Ⅲ (35.5%) , level Ⅵ (28.59%) , level Ⅳ (23.21%) , level Ⅱ (7.18%) and level Ⅴ (7.12%) , suggested that GUA-MRND had higher efficacy for level III, level Ⅵ and Level IV. Conclusion:GUA-MRND is safe, effective, and has high cosmetic satisfaction in the treatment of selected patients with lateral cervical lymph node metastases from papillary thyroid cancer.

Objective:To conduct a retrospective analysis of efficacy and safety of different conversion schemes of tacrolimus to slow-release dosage forms for recipients in stable phase after renal transplantation to provide rationales for the conversion strategy of tacrolimus.Methods:From January 2020 to June 2020, clinical data were reviewed for 101 kidney transplant recipients converting from common tacrolimus dosage form to tacrolimus sustained-release dosage form during postoperative stable period.There were 62 males and 49 females with an age range of 19 to 69 years.They were divided into two groups according to iso-dose and incremental-dose switching schemes.The common dosage form of tacrolimus was converted into a sustained-release dosage form with different conversion doses, They were divided into two groups of 1∶1 conversion( n=55)and >1∶1 conversion( n=46). The clinical parameters of serum creatinine(Scr), blood urea nitrogen(BUN), alanine aminotransferase(ALT)and aspartate aminotransferase(AST), alkaline phosphatase(ALP), serum albumin(ALB), white blood cell count(WBC), urinary white blood cell(UWBC), hemoglobin(Hb)and fasting blood glucose(Glu)were compared between two groups after conversion. Results:Regarding numerical change trend after switching to tacrolimus sustained-release dosage form, drug dose/variation trend was smaller and blood drug concentration more stabilized.In two subgroups converted by 1∶1 and 1>1 initial dose, change trend of dose/blood concentration in 1∶1 conversion group appeared to be more stable.However, no inter-group difference existed in long-term parameters.Scr was lower at 1 week and 3 months after switching to extended-release dosage form( P<0.05)and BUN was lower at 2 weeks( P<0.05). In addition, at 5 months after conversion, ALT and AST significantly improved as compared with common dosage form( P<0.05). Significant differences existed in urinary WBC(UWBC)at 2/3 weeks( P<0.05). After switching for 2 weeks, hemoglobin significantly improved compared with common dosage form( P<0.05). No significant differences existed in ALP, ALB or Glu at other timepoints and pre-conversion( P>0.05). In 1∶1 switch group, renal function tended to improve.At 2 weeks, BUN was lower than pre-conversion; at 1/3 weeks, Scr was lower than pre-conversion( P<0.05). In addition, there was also a trend of improvement in liver function in 1∶1 conversion group.At 1 week and 5 months, ALT was lower than pre-conversion( P<0.05). However, no significant differences existed in AST, ALB, ALP, Glu, UWBC and serum WBC count at each timepoint between two different dose conversion groups( P>0.05). After conversion, intra-individual variability of tacrolimus trough concentration significantly improved( P<0.05). Conclusions:With the same safety and efficacy as common dosage form, sustained-release dosage form of tacrolimus may improve drug variability of individuals.When converting common dosage form into sustained-release dosage form, individual differences should be considered.While monitoring trough concentrations, proper doses should be adjusted on the basis of various clinical parameters.

Objective:To explore the long-term preservation value and repair effect of normothermic machine perfusion (NMP) on clinically discarded kidneys.Methods:A case of clinical discarded donor kidney was collected, and NMP was carried out in vitro for 9 hours with recovered blood. The dynamic changes of renal appearance, blood gas and biochemistry analysis of perfusate and renal pathology were recorded. Results:In the second to fifth hour of NMP, the appearance of renal was pink and ex vivo normothermic perfusion assessment score (EVNP) was grade Ⅰ. While, the sixth hour and beyond of NMP, the appearance of kidney turned to dark red and EVNP was grade Ⅲ. The renal perfusion blood flow maintained above 150 ml/min in the first 6 hours and decreased significantly after that, and at the end, was only 50 ml/min. During the whole process of perfusion, urine output was maintained at about 100 ml/h. PO 2 remained above 100 mmHg in the first 5 hours of perfusion and from the 6th hour, was lower than 80 mmHg and continued to decline, and was close to 0 at the end of perfusion. The results showed that although the K + concentration changes in blood and urine in the first 5 hours of NMP had a good consistency, the lactic acid level had been rising. In addition, there was no significant change in the histopathology at the fourth hour of perfusion compared with that before zero-point puncture, and the fibrinous thrombus in glomeruli was improved compared with that before perfusion. However, at the sixth hour after perfusion and before the end of perfusion, the pathological changes of renal tissue were significantly worse. There were a large of thrombosis in glomerular blood vessels, renal tubular atrophy and acute tubular necrosis. Conclusions:NMP can realize the evaluation of extended criteria donors before transplantation, and it proves the feasibility and repair potential of NMP in kidney to a certain extent. At the same time, NMP also provides a new way to expand the source of donor kidney and to pre-treat organ in vitro.

Objective:To evaluate the value and efficacy of microscope-assisted minimally invasive anterior lumbar discectomy and zero-profile fusion (ALDF) for lumbar degenerative diseases.Methods:Anterior lumbar distractors were designed to maintain the distraction of intervertebral space and expose the posterior edge of the intervertebral space. From June 2018 to December 2020, 41 cases of lumbar degenerative diseases were treated with this operation, including 19 men and 22 women, aged 29-71 years old (average 42.1 years old). All patients had intractable low back pain. Imaging examination showed lumbar disc degeneration with narrow intervertebral space, including disc herniation with Modic changes in 7 cases, spinal stenosis with instability in 16 cases and spondylolisthesis in 18 cases. The involved levels included L 2,3 in 1 case, L 3,4 in 3 cases, L 2-L 4 in 1 case, L 4,5 in 17 cases and L 5S 1 in 19 cases. An incision was taken that was pararectus for L 2-L 4 and transverse for L 4-S 1, with the intervertebral disc exposed via extraperitoneal approach. The intervertebral space was released and distracted after discectomy in intervertebral space, and self-made distractors were used to maintain the space. Under microscope, the herniation, posterior annulus and osteophyte were removed for sufficient decompression, with a suitable self-anchoring cage implanted into the intervertebral space. The visual analogue score (VAS), Oswestry dysfunction index (ODI), intervertebral space height, lordosis angle and spondylolisthesis rate were evaluated. Results:Operations were performed successfully in all the patients. The operation time was 70-120 min with an average of 90 min, and the intraoperative blood loss was 15-70 ml with an average of 30 ml. No severe complication such as nerve or blood vessel injury occurred. The patients were followed up for 12 to 36 months, with an average of 18 months. At the last follow-up, VAS decreased from 6.4±2.3 to 1.1±0.9, and ODI decreased from 44.9%±16.9% to 5.8%±4.7%. Intervertebral space height recovered from 7.2±2.8 mm to 12.1±2.1 mm and lordosis angle recovered from 6.9°±4.8° to 10.1°±4.6°. X-ray showed significant recovery of intervertebral space height, lordosis angle and spondylolisthesis rate, with obvious interbody fusion and no displacement of cage. For 18 patients of spondylolisthesis, the slippage recovered from 16.6%±9.3% to 7.6%±5.3%, with an average improvement of 54.2%.Conclusion:Microscope-assisted minimally invasive ALDF can provide sufficient decompression and zero-profile fusion for lumbar degenerative diseases with satisfactory results during short-term follow-up.

Objective:To investigate the feasibility and clinical effects of thoracic endoscopic-assisted anterior-lateral decompression and fusion for thoracolumbar or upper lumbar disc herniation (LDH) associated with vertebral osteochondrosis (VO).Methods:From December 2017 to December 2019, 10 patients of thoracolumbar or upper LDH associated with VO were treated with thoracic endoscopic-assisted anterior-lateral decompression and fusion, including 6 men and 4 women, with an average 49.2 years old (range, 37 to 65 years old). The involved levels included T 12L 1 in 5 cases, L 1, 2 in 2 cases and L 2, 3 in 3 cases. There were 4 cases of simple thoracolumbar or upper LDH associated with VO and 6 cases of thoracolumbar or upper LDH associated with VO combined with ligamentum flavum hyperplasia and ossification or kyphosis (combined with posterior decompression and internal fixation or posterior correction surgery). The visual analogue scale (VAS), Oswestry disability index (ODI) and anterior and posterior height of intervertebral space were evaluated at follow-up. The clinical effects were evaluated according to the modified MacNab criteria. Results:The operation was performed successfully in all the patients. During the operation, the herniated disc and ossification were clearly exposed and completely removed, with the sufficient decompression of spinal cord, nerve root and dural sac. The operation duration was 115.4±23.8 minutes (range, 70 to 180 mins). Intraoperative bleed loss was 122.6±21.3 ml (range, 40 to 310 ml). The patients were followed up for averagely 21.6 months (range, 12 to 36 months). At the final follow-up, VAS score decreased from preoperative 7.2±1.9 to 1.8±1.1, and ODI decreased from preoperative 64.3%±13.9% to 16.3%±5.1% ( P<0.05). The anterior height of intervertebral space recovered from preoperative 7.8±1.5 mm to 11.9±2.3 mm, and the posterior height of intervertebral space recovered from preoperative 4.5±1.1 mm to 7.4±1.6 mm ( P<0.05). According to modified MacNab criteria, the results were excellent in 9 cases and good in 1 case. Conclusion:For thoracolumbar or upper LDH associated with VO, thoracic endoscopic-assisted anterior-lateral decompression and fusion provided clear vision of the surgical field, fully exposed and completely removed the herniated disc and ossification, which achieved satisfactory short-term results.

Objective:To evaluate the efficacy of self-anchored lateral lumbar interbody fusion (SA-LLIF) for lumbar degenerative diseases.Methods:During January to December in 2019, a total of 41 patients with lumbar degenerative disease were treated with SA-LLIF, included 18 males and 23 females, aged 59.6±11.3 (range 49-77) years. There were lumbar stenosis and instability in 17 cases, disc degenerative disease in 8 cases, degenerative spondylolisthesis in 8 cases, degenerative scoliosis in 5 cases, postoperative revision in 3 cases. And osteoporosis was diagnosed in 5 of them. The index level included L 2, 3 in 2 cases, L 3, 4 in 11 cases, L 4, 5 in 20 cases, L 2-L 4 in 3 cases and L 3-L 5 in 5 cases. After general anesthesia, the patient was placed in decubitus position. The anterior edge of psoas major muscle was exposed through 6 cm incision and extraperitoneal approach. Further, the psoas major muscle was properly retracted to expose the disc. After discectomy, the intervertebral space was prepared and moderately distracted. A suitable fusion cage filled with auto iliac graft was implanted. Two anchoring plates were inserted into the cage. Then, the caudal and cephalic vertebral body and the fusion cage were locked. Results:The operation was performed successfully in all the patients. The operation duration was 79.0±19.5 (range 60-100) min. Intraoperative bleed loss was 38.0±28.2 (range 15-70) ml. The patients were followed up for averagely 10.6±4.6 (range 4-15) months. The visual analogue scale decreased from preoperative 6.2±2.1 to 1.6±1.1 and Oswestry disability index decreased from 47.8%±15.1% to 11.0%±7.3%. X-ray showed that the spine alignment recovered satisfactorily. No cage displacement was found. Sinking (2-3 mm) of cage was found in 7 patients without obvious symptom despite transient lumbar pain in an obesity woman. The lumbar lordosis recovered from 36.4°±10.2° to 48.0°±10.7°, and intervertebral height recovered from 8.3±2.5 mm to 11.3±3.3 mm. The rate of spondylolisthesis recovered from 19.7%±4.4% to 9.3%±5.3%.Conclusion:SA-LLIF can provide immediate stability and good results for lumbar degenerative diseases with stand-alone anchoring cage without posterior internal fixation.

Objective:To evaluate the value and efficacy of self-anchored anterior lumbar discectomy and fusion (SA-ALDF) for L 5 isthmic spondylolisthesis. Methods:From June 2018 to December 2019, a total of 11 cases of L 5 isthmic spondylolisthesis were treated with SA-ALDF, including 4 men and 7 women, aged 43.2±12.6 (range 29-63) years. All patients had intractable low back pain aggravating during standing activities and alleviating during rest, without lower extremity radicular symptoms. Imaging examination showed bilateral isthmus cleft of L 5 with spondylolisthesis of 1 degree in 10 cases and 2 degree in 1 case according to Meyerding grading system. Under general anesthesia and supine French position, transverse 6 cm incision was made. Then, the L 5S 1 intervertebral disc was exposed via extraperitoneal approach between the bifurcation of abdominal aorta and vena cava. The intervertebral disc was sufficiently removed. The intervertebral space was released and distracted followed by canal ventral decompression and sequential mold testing. Suitable self-anchoring cage filled with auto iliac cancellous bone was implanted to restore intervertebral height and lordosis as well as reduction of spondylolisthesis. Under fluoroscopic guidance, the distal anchoring plate was knocked into the sacrum followed by direct reduction and proximal anchoring plate locking in the L 5 vertebral body. The patients were followed up for 12.1±4.7 (range 6-18) months. The visual analogue score (VAS) and Oswestry dysfunction index (ODI) were evaluated. The reduction and fusion were evaluated on the X-ray films. Furthermore, the rate of spondylolisthesis, the height and the lordosis of intervertebral space were measured. Results:The operation was performed successfully in all the patients with operation duration 90±18 (range 70-120) min, intraoperative blood loss 30±16 (range 10-60) ml. No severe complication such as nerve and blood vessel injury occurred. All patients experienced alleviation of symptom during follow-up. X-rays confirmed that the spondylolisthesis and alignment were recovered obviously without obvious cage displacement. However, the loss of reduction was 63.2% for the grade 2 spondylolisthesis. At the final follow-up, VAS decreased from 6.1±2.1 to 0.9±0.5, ODI decreased from 43.6%±14.2% to 6.0%±3.4%. The spondylolisthesis recovered from 17.7%±10.3% to 8.0%±7.2% with reduction rate of 54.8%±21.6%. The interverbral height recovered from 6.4±2.1 mm to 9.8±3.9 mm and intervertebral lordosis recovered from 4.8°±2.9° to 9.6°±4.7°.Conclusion:SA-ALDF can provide satisfactory outcomes for selected L 5 isthmic spondylolisthesis of degree 1 without neurological compromise. However, its mechanical stability may be insufficient for isthmic spondylolisthesis of degree 2.