Tongxie Yaofang Regulates Expression of NKG2DL to Enhance Anti-tumor Effect of NK Cells in Colon Cancer under Chronic Stress / 中国实验方剂学杂志

ObjectiveTo observe the effect of Tongxie Yaofang on the function of tumor-related natural killer （NK） cells under chronic stress and explore the possible molecular mechanism. MethodFifty SPF-grade BABL/C male mice were randomized into normal， model， and low-， medium-， and high-dose （6.825， 13.65， and 27.3 g·kg-1， respectively） Tongxie Yaofang groups， with 10 mice in each group. Other groups except the blank group were subjected to 7 days of chronic restraint stress， and then forced swimming and tail suspension tests were carried out to evaluate the modeling performance. After the successful modeling， rats in Tongxie Yaofang groups were administrated with low-， medium-， and high-doses of Tongxie Yaofang by gavage， while those in the other groups were administrated with normal saline by gavage. After 14 days， each group of mice was inoculated with subcutaneous colon cancer to establish the model of colon cancer under chronic stress. The pathological changes of the tumor tissue in each group of mice were observed using hematoxylin-eosin （HE） staining. The content of CD49b-positive cells in the peripheral blood and tumor tissue of mice was measured by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the content of molecules associated with NK cell activation in the peripheral blood. Western blot was employed to determine the protein levels of major histocompatibility complex class Ⅰ polypeptide-related sequences A and B （MICA+MICB） and UL-16-binding protein 1 （ULBP1） in the tumor tissue. ResultCompared with the normal group， the model group showed a decrease in 5-hydroxytryptamine （5-HT） content and an increase in corticosterone （CORT） content in the serum （P<0.05）. Compared with the model group， Tongxie Yaofang increased the 5-HT content and decreased the CORT content （P<0.05， P<0.01）. Compared with the normal group， the modeling increased the tumor volume and weight （P<0.05）， while Tongxie Yaofang inhibited such increases with no statistical significance. The tumor cells in the model group presented neat arrangement， irregular shape， uneven size， obvious atypia， common nuclear division， and small necrotic area， and blood vessels were abundant surrounding the tumor cells. Compared with the model group， Tongxie Yaofang groups showed sparse arrangement of tumor cells， different degrees of patchy necrosis areas in the tumor， and karyorrhexis， dissolution， and nuclear debris in the necrotic part. Compared with the normal group， the model group showed reduced CD49b-positive cells in the peripheral blood and tumor tissue （P<0.01）. Compared with the model group， Tongxie Yaofang increased CD49b-positive cells （medium dose P<0.01， high dose P<0.05， P<0.01）. Compared with the normal group， the modeling lowered the serum levels of granzymes-B （Gzms-B）， perforin （PF）， interferon （IFN）-γ， and tumor necrosis factor （TNF）-α （P<0.05， P<0.01）. Compared with the model group， low-dose Tongxie Yaofang elevated the serum levels of PF， Gzms-B， and TNF-α （P<0.05， P<0.01）， and medium-dose Tongxie Yaofang elevated the serum levels of Gzms-B， PF， IFN-γ， and TNF-α （P<0.05， P<0.01）. In addition， high-dose Tongxie Yaofang elevated the serum levels of PF， IFN-γ， and TNF-α （P<0.01）. Compared with the normal group， the model group presented down-regulated protein level of ULBP1 （P<0.05）. Compared with the model group， low-， medium-， and high-dose Tongxie Yaofang up-regulated the protein level of ULBP1 （P<0.05， P<0.01）， and medium- and high-dose Tongxie Yaofang up-regulated the protein level of MICA+MICB （P<0.05， P<0.01）. ConclusionTongxie Yaofang may promote NK cell activation by up-regulating the expression of MICA+MICB and ULBP1， thereby delaying the progression of colon cancer under chronic stress.

Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Distal tibiofibular syndesmosis fibular notch typing and its clinical significance based on CT / 解剖学报

Objective To investigate the morphological typing and clinical significance of the distal tibiofibular syndesmosis fibular notch based on CT images. Methods According to the inclusion and exclusion ceiteria‚ the imaging data of patients undergoing ankle joint CT examination were analyzed‚ and the inferior tibiofibular joint fibula notch was classified according to the morphological characteristics. The measurements included 8 distances. There were 123 males and 102 females‚ all of whom were Han nationality‚ aged 18-60 years old. Results Retrospectively analyzed the result of 225 patients from December 2013 to December 2022. The distal tibiofibular syndesmosis fibular notch was divided into four types according to morphological characteristics‚ C-shaped (50. 67%)‚ V-shaped (26. 67%)‚ flat-shaped (15. 11%) and L-shaped (7. 56%). The angle between the anterior and posterior facets of the flat shape (145. 56 ± 9. 25)° was the largest and the angle between the anterior and posterior facets of the L shape (125. 07 ± 13. 54)° was the smallest(P< 0. 05); the depth of the notch in the flat shape (3. 11 ± 0. 83) mm was the smallest and in the L shape (4. 47±1. 11) mm was the largest(P<0. 05);The posterior facet length (13. 06 ± 3. 56) mm and anterior tibiofibular gap (3. 83±1. 49) mm on left were larger than on the right side (P<0. 05); The posterior facet length (13. 36 ± 3. 46) mm‚ fibular notch depth (3. 93 ± 1. 10) mm and vertical distance of tibiofibular overlap (9. 10 ± 2. 55) mm larger in men than in women (P<0. 05). Conclusion In this study‚ the data related to the inferior tibiofibular syndesmosis notch were measured and divided into four types according to the shape. The flat inferior tibiofibular syndesmosis notch is more likely to have chronic ankle instability‚ and the fibula is more likely to move forward during anatomical reduction. The inferior tibiofibular syndesmosis of L-shaped and C-shaped notches is more prone to posterior displacement of fibula or poor rotation reduction during anatomical reduction.

Association between index finger and ring finger length ratios and polymorphism of homeobox A11 gene locus among Ningxia college students / 解剖学报

Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.

Multisensory Conflict Impairs Cortico-Muscular Network Connectivity and Postural Stability: Insights from Partial Directed Coherence Analysis / 神经科学通报·英文版

Sensory conflict impacts postural control, yet its effect on cortico-muscular interaction remains underexplored. We aimed to investigate sensory conflict's influence on the cortico-muscular network and postural stability. We used a rotating platform and virtual reality to present subjects with congruent and incongruent sensory input, recorded EEG (electroencephalogram) and EMG (electromyogram) data, and constructed a directed connectivity network. The results suggest that, compared to sensory congruence, during sensory conflict: (1) connectivity among the sensorimotor, visual, and posterior parietal cortex generally decreases, (2) cortical control over the muscles is weakened, (3) feedback from muscles to the cortex is strengthened, and (4) the range of body sway increases and its complexity decreases. These results underline the intricate effects of sensory conflict on cortico-muscular networks. During the sensory conflict, the brain adaptively decreases the integration of conflicting information. Without this integrated information, cortical control over muscles may be lessened, whereas the muscle feedback may be enhanced in compensation.

The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells / 中华创伤杂志(英文版)

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Cancer genomics and precision medicine / 药学学报

It has been noted for decades that cancer is essentially a genomic disease. Benefiting from the latest development of high-throughput sequencing and bioinformatics technologies, a variety of genetic alterations have been identified for their roles in cancer occurrence and development, giving rise to new opportunities for anti-cancer drug discovery. In particular, the rapid advancement of cancer genomics has paved the way for the precision medicine that has gained compelling achievement in the past years and significantly benefited cancer patients. In this review, we summarize the main types of genomic abnormalities in cancer, the application of functional genomics research in cancer research, and in particular the translational application of cancer genomics in clinical diagnosis, drug discovery and cancer precision medicine. With this review, we hope to better understand cancer genomics research and provide future perspectives for its application in precision medicine.

Network Meta-analysis of Qi-supplementing and Yin-nourishing Chinese patent medicines in treatment of early diabetic nephropathy / 中国中药杂志

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.

Decursin affects proliferation, apoptosis, and migration of colorectal cancer cells through PI3K/Akt signaling pathway / 中国中药杂志

We investigated the effects of decursin on the proliferation, apoptosis, and migration of colorectal cancer HT29 and HCT116 cells through the phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway. Decursin(10, 30, 60, and 90 μmol·L~(-1)) was used to treat HT29 and HCT116 cells. The survival, colony formation ability, proliferation, apoptosis, wound hea-ling area, and migration of the HT29 and HCT116 cells exposed to decursin were examined by cell counting kit-8(CCK8), cloning formation experiments, Ki67 immunofluorescence staining, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blot was employed to determine the expression levels of epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2-associated X protein(Bax), tumor suppressor protein p53, PI3K, and Akt. Compared with the control group, decursin significantly inhibited the proliferation and colony number and promoted the apoptosis of HT29 and HCT116 cells, and it significantly down-regulated the expression of Bcl-2 and up-regulated the expression of Bax. Decursin inhibited the wound healing and migration of the cells, significantly down-regulated the expression of N-cadherin and vimentin, and up-regulated the expression of E-cadherin. In addition, it significantly down-regulated the expression of PI3K and Akt and up-regulated that of p53. In summary, decursin may regulate epithelial-mesenchymal transition(EMT) via the PI3K/Akt signaling pathway, thereby affecting the proliferation, apoptosis, and migration of colorectal cancer cells.

Progress in clinical studies in cardiovascular surgery 2022 / 中国胸心血管外科临床杂志

@#In 2022, many excellent clinical studies emerged in the field of cardiovascular surgery. Selecting papers published in The New England Journal of Medicine and other top medicine and cardiology journals, this review focused on the research progress on 7 topics in the field of cardiovascular surgery: coronary artery surgery, vascular surgery, valvular surgery, structural heart disease, congenital heart disease, heart transplantation, perioperative management, and special population.

Analysis of typical experiences of public hospital salary system reform in Sichuan province / 中华医院管理杂志

Objective:To analyze the experiences and practice in the reform of public hospital salary system in Sichuan province, summarize the typical modes of such reform in the province, and provide references for further reform.Methods:As of October 29, 2021, the research group received 77 sets of typical experience materials submitted by the health commissions and public hospitals in Sichuan province on enforcing the reform of the public hospital salary system. The analysis framework was based on the five main elements proposed in the Guidance to Deepening the Reform of the Salary System of Public Hospitals for the purpose of furthering the reform. These five elements refer to " reasonably determining the level of salary in public hospitals" " fully implementing the autonomy of internal distribution in public hospitals " " establishing and improving the incentive and restraint mechanism for the remuneration of public hospital leaders" " improving the assessment and evaluation mechanism oriented to public welfare" and " funding sources ". A quantitative analysis was made on the typical experience materials using the social network analysis method, while a qualitative analysis was made on the typical experience materials using the content analysis method. Results:The results of social network analysis showed that the network density was 0.272; the highest point centrality was " fully implement the autonomy of internal distribution in public hospitals" (0.935), and the highest intermediary centrality was " improving the assessment and evaluation mechanism oriented to public welfare" (0.870), while the closeness to centrality of " establishing and improving the incentive and constraint mechanism for the salary of public hospital leaders" (0.434) and " funding sources" (0.421) were relatively low. The results of content analysis showed that the ones with higher frequency among all the typical experience materials were " fully implementing the autonomy of internal distribution of hospitals" (72 times) and " improving the assessment and evaluation mechanism oriented to public welfare" (67 times), while the ones with lower frequency were " establishing and improving the salary incentive and constraint mechanism for public hospital leaders" (17 times) and " funding sources" (14 times). In terms of unity and synergy, the typical models of public hospital salary system reform in the province could be categorized as the fine standard mode, the fair value mode, the autonomous synergy mode and the circular symbiosis mode.Conclusions:Deepening the reform of the salary system of public hospitals should unify the standards and improve the fair and refined assessment and evaluation mechanism; explore various forms of distribution and build an internal autonomous and synergistic incentive mechanism; pay attention to the weak remuneration incentive mechanism for hospital leaders and the problem of a relatively single source of funding.

The influence of COVID-19 infection on treatments of patients with acute type A aortic dissection / 中华胸心血管外科杂志

Objective:To investigate the differences in outcomes of surgical strategies and prognosis of patients with acute type A aortic dissection(ATAAD) during the period of COVID-19 Omicron variant epidemic compared with the non-epidemic period.Methods:Clinical data were retrospectively collected from ATAAD patients during the COVID-19 Omicron variant epidemic(December 7, 2022 to January 10, 2023) and during the non-epidemic period(December 7, 2019 to January 10, 2020) to compare the differences in surgical strategies, perioperative mortality, and perioperative complication rates in ATAAD patients during the two different periods.Results:There were 14 patients in the COVID-19 infected group and 43 patients in the control group. Patients in the infected group had a shorter mean aortic clamp time[(89.71±16.27)min vs.(110.09±28.99)min, P<0.01], a significantly higher postoperative mortality rate relative to the control group(21.43% vs. 2.33%, P=0.02), a significantly longer length of stay in the ICU(3 days vs. 2 days, P=0.04) and the duration of intubation time(34 h vs. 14 h, P<0.01), and the incidence of adverse events, mainly cerebral infarction, was higher in infected group(28.57% vs. 6.98%, P=0.03). Conclusion:During the COVID-19 Omicron variant strain epidemic, our center preferred a more conservative surgical strategy in COVID-19 infected patients. Although the COVID-19 infection increased the postoperative mortality and complication rate of ATAAD, patients still achieve a more satisfactory outcome. Therefore, surgical treatment should be timely performed for ATAAD patients.

Advances in the establishment and evaluation of animal models of secondary lymphedema / 中华显微外科杂志

Secondary lymphedema is a chronic progressive disease caused by the obstruction of lymphatic reflux, which leads to a series of secondary affection. There is no cure at present. Exploring the pathogenesis and treatment of lymphedema is based on animal models that mimic the pathophysiology of chronic lymphedema in humans. Currently, there are many known animal models of lymphedema, such as the limb lymphedema model of mice, dogs and other animals, and the rabbit ear lymphedema model. But most of them cannot induce the persistent and stable lymphedema temporarily, which lead to a deadlock in the related research progress. Therefore, it is necessary to improve and even create new animal models of lymphedema. This paper summarises the progress of relevant literature and provides references for further improving the establishment of a lymphedema animal model. It also summarise existing methods for evaluating lymphedema or lymphatic vessel function to provide an evaluation tool for modified or new animal models.

Analysis of clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease stage 3-4 / 中华肾脏病杂志

Objective:To explore the clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease (CKD) stage 3-4.Methods:It was a single-center, retrospective observational study. CKD stage 3-4 patients aged ≥60 years old from March 2019 to March 2022 in the Geriatrics Department of the First Affiliated Hospital of Zhengzhou University were enrolled in the study. General data of the patients were collected, and laboratory indicators, muscle strength, physical function and appendicular muscle mass index (ASMI) were measured. According to the diagnostic criteria of sarcopenia, the patients were divided into no sarcopenia CKD group and sarcopenia CKD group. Baseline data between these two groups were compared. Logistic regression analysis was used to analyze the related factors of sarcopenia in elderly CKD stage 3-4 patients.Results:A total of 162 CKD stage 3-4 patients were enrolled in this study, with 89 males (54.9%) and a median age of 75 (69, 82) years. Sarcopenia was diagnosed in 40 cases, and the prevalence was 24.7% (95% CI 18.1%-31.3%). Compared with no sarcopenia CKD group, age, proportion of dementia, cystatin C, urea nitrogen, C-reactive protein (CRP) and ratio of urine protein to creatinine were higher (all P<0.05), while body mass index (BMI), hemoglobin, carbon dioxide combining power, estimated glomerular filtration rate (eGFR), serum albumin and the proportion of regular exercise and using α-ketones were lower in sarcopenia CKD group (all P<0.05). Meanwhile, grip strength, walking speed, short physical performance battery score and ASMI were lower in sarcopenia CKD group (all P<0.05). Multivariable logistic regression analysis results showed that low eGFR ( OR=0.824, 95% CI 0.687-0.987, P=0.036), low BMI ( OR=0.463, 95% CI 0.304-0.704, P<0.001), low serum albumin ( OR=0.459, 95% CI 0.263-0.802, P=0.006) and high CRP ( OR=2.754, 95% CI 1.708-4.439, P<0.001) were the independent related factors of sarcopenia in elderly CKD patients. Conclusions:The prevalence of sarcopenia in elderly CKD stage 3-4 patients is high. Low eGFR, low BMI, low serum albumin and high CRP are the independent risk factors for sarcopenia in elderly CKD stage 3-4 patients.

Research progress on involvement of pedunculopontine tegmental nucleus in dystonia / 中华神经科杂志

As the major part of mesencephalic locomotion region, pedunculopontine tegmental nucleus (PPN) participates in motor initiation, rhythmic and speed regulation. In addition, PPN is regarded as a novel deep brain stimulation target for patients with Parkinson′s disease due to its dramatic effect on the gait disturbance and postural instability. However, PPN also has an important role in muscle tone control and dystonia. This review is aimed at summarizing the involvement of PPN in dystonia, providing fundamental for targeting PPN for treatment of dystonia in the future.

The 499th case: Roux-en-Y gastric bypass, limb weakness, and ostealgia / 中华内科杂志

A 36-year-old woman was admitted to the Peking Union Medical College Hospital with a history of fractures for 2 years, limb weakness for 1 year, and ostealgia for 2 months. The patient's examination identified iron deficiency anemia, significantly decreased serum calcium and 25-hydroxyvitamin D3 levels, and increased alkaline phosphatase and parathyroid hormone levels. Imaging showed several typical signs of osteomalacia. Considering the history of Roux-en-Y gastric bypass surgery, the diagnosis was considered to be osteomalacia caused by a postoperative nutritional absorption disorder. The patient was supplemented with calcitriol, calcium, and vitamin D and gradually returned to normal physical activity. The bone metabolism indicators and bone density were significantly improved.

Effect of Edaravone and dexborneol on oxidative stress pathway in peripheral blood of elderly patients with acute ischemic stroke / 中华老年医学杂志

Objective:To investigate the effect of Edaravone and dexborneol(Eda.B)on oxidative stress pathway in peripheral blood of elderly patients with acute ischemic stroke.Methods:A total of 87 elderly patients with acute ischemic stroke in the Department of Neurology, Qinghai University Affiliated Hospital from July 2021 to January 2022 were selected as the study subjects.According to the random number table, they were divided into control group(44 cases)and edaravone dexborneol group(43 cases). Each group was divided into <12 h group, 12-24 h group and 24-48 h group according to the time of onset.Peripheral blood was collected in each group at admission and discharge, respectively.The serum levels of reactive oxygen species(ROS), Kelch-like epichlorohydrin-associated protein 1(Keap1), nuclear factor-E2-associated factor 2(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6), as well as superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were detected.Results:Elderly patients with acute ischemic stroke receving Eda.B treatment after admission could reduce the serum concentration of ROS, TNF-α and IL-6, as well as MDA content, and increase the concentration of Keap1, Nrf2, HO-1 and NQO1 and SOD activity.Except for ROS concentration in <12 h group and SOD activity in <12 h and 12 h-24 h groups, the differences between the other groups were statistically significant( P<0.05 for all). Compared with the control group, the serum concentration of TNF-α and IL-6 of patients in the Eda.B group at discharge decreased, while the concentration of Nrf2(24-48 h group)and HO-1(24-48 h group), and SOD activity increased, the differences were statistically significant( P<0.05 for all). In the control group at discharge, the concentrations of ROS(24-48 h group), TNF-α(<12 h group, 24-48 h group)and IL-6, as well as MDA content decreased, while the concentrations of Keap1, Nrf2(<12 h group, 12-24 h group)and HO-1(<12 h group, 12-24 h group)increased, the differences were also statistically significant( P<0.05 for all). Compared with admission, the concentration of Keap1(24-48 h group)and HO-1(24-48 h group), the activity of SOD(<12 h group, 12-24 h group)increased and the content of MDA(12-24 h group)in the Eda.B group decreased at discharge( P<0.05 for all). Conclusions:Eda.B can reduce oxidative stress and inflammatory response in peripheral blood of elderly patients with acute ischemic stroke by acting on the Keap1/Nrf2 pathway.

Application of three-dimensional printed endoprosthesis for reconstruction after metaphysis-involved intercalary tumor resection / 中华骨科杂志

Objective:To describe the design, manufacture and use of three-dimensional (3D)-printed endoprosthesis for reconstruction after metaphysis-involved intercalary tumor resection and to evaluate its outcome.Methods:Forty-three patients who received metaphysis-involved intercalary tumor resection followed by 3D-printed endoprosthetic reconstruction in Musculoskeletal Tumor Center, Peking University People's Hospital between January 2018 and December 2021 were retrospectively reviewed. There were 25 males and 18 males with an average age of 20.1±15.2 years (range, 4-58 years). The pathological diagnosis included 24 cases of osteosarcomas, 6 cases of Ewing sarcomas, 5 cases of chondrosarcomas, 2 cases of pleomorphic undifferentiated sarcomas, 3 cases of soft-tissue sarcomas (liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor for each) and 3 others (adamantinoma, recurrent aneurysmal bone cyst and recurrent osteofibrous dysplasia for each). The tumors located at femur in 25 patients (58%), including 14 lesions involving distal femoral metaphysis and 11 lesions involving both proximal and distal metaphysis; the tumors located at tibia in 11 patients (26%), including 4 lesions involving distal tibial metaphysis, 5 lesions involving proximal tibial metaphysis and 2 lesions involving both proximal and distal tibial metaphysis; the tumors located at humerus in 7 patients (16%), including 1 lesion involving distal humeral metaphysis, 3 lesions involving proximal humeral metaphysis and 3 lesions involving both proximal and distal humeral metaphysis. The endoprosthesis was designed in a semi-modular fashion and consisted of three parts: a diaphysis-fixing component, a semi-modular lap joint component, and a custom-made 3D-printed metaphysis-fixing component which was designed as two types with 3D-printed porous bone-contacting surfaces according to the osteotomy plane (Type I on meta-diaphyseal region, Type II on meta-epiphyseal region). The functional outcome was assessed using Musculoskeletal Tumor Society (MSTS) 93 system.Results:All surgeries were accomplished sucessfully. The median resection length and the distance from osteotomy plane to adjacent joint was 16.0 (13.0, 22.0) cm and 4.5 (3.5, 6.0) cm, respectively. 59 metaphysis-fixing components were installed in 43 patients. Type I components were used in single and dual ends of endoprosthesis in 12 and 6 cases respectively. Type II components were used in single and dual ends in 15 and 5 cases respectively. Hybrid endoprosthesis with Type I and II components were used in 5 cases. The mean follow-up time was 26.0 (17, 37) months (range, 12-54 months). The mean MSTS 93 score was 29.0 (28.0, 30.0) points (range, 21-30 points). Implant failures were found in 5 patients, including 2 cases of aseptic loosening (loosening was observed in the cementing diaphysis-fixing stems while no evidence of loosening in metaphysis-fixing components) and 3 cases of local tumor progression. The 2-year implant survival rate was 90.3% (95% CI: 0.81, 0.99). Conclusion:Using 3D-printed intercalary endoprosthesis for reconstruction after intercalary resection of metaphysis-involved bone tumor shows satisfactory functional outcome and implant survival. Moreover, by assembling endoprosthetic components according to the different osteotomy plane, the semi-modularized endoprosthesis also provids a comprehensive and individualized reconstruction for patients with metaphysis-involved intercalary tumor.

Application of newly designed modular hinged ankle prosthesis in the reconstruction of defect after surgical treatment of malignant tumor at the distal tibia / 中华骨科杂志

Objective:To investigate the outcome of surgical treatment of malignant tumor at the distal tibial after reconstruction with modular hinged ankle prosthesis.Methods:The data of 9 patients with malignant tumor at the distal tibia at Musculoskeletal Tumor Center of PKUPH from June 2020 to November 2021 were analyzed retrospectively. They were male patients with age of 17 (14, 24) years (range 11-56 years). There were five tumors at the left sides and four at the right sides. There were eight patients with osteosarcoma who received the neo-chemotherapy. Among eight osteosarcomas, one was Enneking IIA and seven Enneking IIB. Furthermore, there was only one patient with renal carcinama and with solitary metastatic lesion at the distal tibia. After the resection of tumor at the distal tibia, talus cartilage was removed and talus component was fixed by lag screws. The proper tibia component was used to restore the defect of tibia and the reduction of tibia and talus components were performed. The following clinical data were collected: baseline demographic features, surgical and follow-up data. The baseline demographic features included gender, age, side, lung or/and other metastasis at initial diagnosis, Enneking stage or systematic progression for renal carcinama, histological type. The surgical data included: surgery time, blood loss, length of bone involved by the tumor, prosthesis type. Monitoring data was also recorded: complications (ankle pain when loading, talar collapse, component loosing, infection and wound dehiscence), local recurrence, pulmonary and systematic metastasis, radiological image and the function at the last follow-up (MSTS and VAS evaluation).Results:Among these nine patients, the average blood loss was 245.6±103.9 ml (range 100-400 ml) and the mean surgery time was 178.9±56.9 mins (range 120-300 min). No patient was lost during the follow-up period and the average follow-up was 21.4±5.6 months (range 12.5-27.2 months). The excision length of tibia was 14 (11, 17) cm (range 11-28 cm). There were one case with 2# prosthetic base, three cases with 3# and five cases with 4#. Five had cement fixation of prosthetic stem and four had the pressing fixation. No pulmonary and other organ metastasis occurred among eight patients with osteosarcoma and one patient with distal tibia matastasis of renal carcinama. One patient with OShad the local recurrence and received the resection. One sustained the deep infection after four months and received the removal of prosthesis and spacer implant. At the final follow-up, except one with deep infection and receiving the removal of prosthesis and spacer implant, eight patients were assessed for the function. The average MSTS was 97.1%±3.3% (range 93%-100%). The VAS of all patients was 0. One patient with prosthesis removal had no functional evaluation. At the final follow-up, all patients walked without crutch. No breakage and loosening of prosthetic stem, talar collapse, prosthetic sinking and ankle pain occurred at the final follow-up.Conclusion:The early satisfactory outcome can be obtained for patients with segmental defect after resection of malignant tumor at the distal tibia, who received the newly designed modular hinged ankle prosthesis. Meanwhile, it's worth promoting in the reconstruction of large segmental defect at the distal tibia.

Physeal-sparing distal femur megaprothesis for skeletally immature patients with osteosarcoma / 中华骨科杂志

Objective:To evaluate the clinical outcome of a special physeal sparing knee prosthesis for pediatric distal femoral osteosarcoma regarding the functional outcome, retention of the growth potential of the proximal tibia, and postoperative complications.Methods:A retrospective study was conducted to review 37 pediatric patients with osteosarcoma of distal femur who were treated in a single musculuskeletal tumor center between August 2015 and January 2019. Among them, 21 were boys and 16 were girls, aged from 5 to 12 years at the time of operation, with an average age of 9.1±2.1 years and the height of 115 to 160 cm, with an average of 140±10 cm. Tumor resection of distal femur was performed and the bone defect was reconstructed by a special hinged knee prosthesis which can preserve the proximal tibial epiphyseal plate. Demographic data was recorded. Overall leg length and tibial length was assessed by full-length standing anteroposterior radiographs of bilateral lower extremity with the patella pointing anteriorly preoperativelly and postoperativelly at each follow up. And the growth potential of the affected proximal tibia was calculated by comparing with the preoperative length of tibia. Meanwhile, the functional outcome was assessed by using the Musculoskeletal Tumor Society (MSTS) system, and the postoperative complications were analysed.Results:All patients underwent the tumor resection and reconstruction operation successfully. The average operation duration was 143±41 minutes, ranging 90 to 250 minutes. The average intraoperative blood loss was 314±397 ml, ranging 30 to 2 200 ml. The patients were followed up for 24 to 64 months, averaging 42.3±12.1 months. The postoperative knee range of motion was 100-130 degrees, with an average of 115.6±7.2 degrees. The postoperative MSTS score was 23-30, with an average of 26.7±1.6. To the last follow-up, the limb length discrepancy of the lower limb was 1.3 to 10 cm, and the length of the tibia was shortened from 0 to 3.8 cm compared with the opposite side, with an average of 1.3±1.0 cm. The growth percentage of the proximal tibial epiphysis on the affected side was 30% to 100%, with an average of 70%±17%. Totally, 13 patients suffered postoperative complication, the overall incidence of complications was 35% (13/37), and prosthesis-related complications were 16% (6/37). Three patients with wound dehiscence were managed by debridement and antibiotics. Radiographs revealed femoral stem loosening in a single patient 3 years after the initial operation and then the prosthesis was converted to an adult tumor knee endoprosthesis. Two cases experienced breakage of the femoral stem at 30 and 33 months, respectively, due to an accidental injury. They received revision surgery, and a new femoral prosthesis component was replaced. One patient developed femoral stem breakage at 10 months after surgery due to fatigue fracture, which treated with revision surgery. Tumor recurrence occurred in 6 patients. Among them, tumor recurrence in soft tissue occurred in 4 patients, and treated with regional resection without further recurrence. The other 2 patients experienced tumor recurrence at the distal femoral site, and treated with resection and prosthetic revision.Conclusion:The physeal sparing pediatric knee prosthesis can preserve the growth potential of the proximal tibial epiphyseal plate with good postoperative function and low incidence of prosthesis complications. Therefore, it can be an alternativeespecially for skeletally immature patients with distal femur osteosarcoma.