Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-β-induced epithelial-mesenchymal transition via directly targeting TGFβR1

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.

Guidelines for management of pediatric acute hyperextension spinal cord injury / 中华创伤杂志(英文版)

Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.

Regulating anaerobic metabolism and promoting myocardial ischemia-hypoxia injury by diesel particulate matter and its key component benzoapyrene via targeting oxygen sensors / 环境与职业医学

Background The exposure to diesel particulate matter (DPM) and its polycyclic aromatic hydrocarbons (PAH) is closely related to the morbidity and mortality of ischemic heart disease (IHD). However, it is unclear what key components and targets of DPM exposure involve in myocardial ischemia-hypoxia injury and associated mechanisms. Objective To identify key PAH components of DPM that act on myocardial hypoxic injury, andclarify the role of oxygen sensors-regulated anaerobic metabolism in DPM and key components-induced hypoxic injury and the targets of the key PAH components. Methods Human cardiomyocyte cell line AC16 cells were exposed to 0, 1, 5, and 10 μg·mL−1 DPM in a high glucose DMEM medium with 10% fetal bovine serum (FBS) (HGM) or low FBS (0.5%) in high glucose DMEM medium (LFM), for 12 h under 2% O2, and expression of hypoxia-inducible factor-1α (HIF-1α), Bax, and Cleaved-caspase3 was determined by Western blotting. Under normal condition, the cell viability was detected after PAH exposure for 12 h. Under the condition of ischemia-hypoxia model, cells were exposed to 0, 0.005, 0.5, and 5 µg·mL−1 PAH for 12 h, and the protein expression of HIF-1α, Bax, and Cleaved-caspase3 was determined. After exposure to DPM or PAH for 12 h, the contents of pyruvate and lactate in cells were detected. Pretreatment with glycolysis inhibitor GSK2837808A was used to explore the role of glycolysis in DPM and benzo[a]pyrene (BaP)-induced hypoxia injury. A molecular docking technique was used to analyze the binding affinity between PAH and oxygen sensors (prolyl hydroxylase domain-containing protein 2, PHD2, and factor-inhibiting hypoxia-inducible factor 1, FIH1), and the protein levels of PHD2, FIH1, and hydroxyl-HIF-1-alpha (OH-HIF-1α) after the DPM or BaP treatment were further determined. Results Under hypoxia, DPM exposure in the LFM induced the expression of HIF-1α, Bax, and Cleaved-caspase3 (P<0.01). Therefore, hypoxia and LFM were selected as the basic ischemia and hypoxia condition. Except for anthracene (Ant) (P>0.05), other PAH decreased cell viability when the concentration was above 1 μg·mL−1 (P<0.05). All concentrations of BaP induced the expression of HIF-1α protein (P<0.05), and the protein levels of Bax and Cleaved-caspase3 were up-regulated after the 0.5 and 5 µg·mL−1 BaP exposure (P<0.01). After exposure to DPM (1, 5 and 10 μg·mL−1) or BaP (0.5 and 5 μg·mL−1), the intracellular pyruvate and lactate contents increased (P<0.05). The glycolysis inhibitor co-treatment decreased the levels of HIF-1α, Bax, and Cleaved-caspase3 proteins compared with the DPM or BaP exposure group for 12 h (P＜0.05). The binding abilities of the five PAHs to the oxygen sensors PHD2 and FIH1 were strong, and BaP was the strongest. Although the DPM or BaP exposure had no effects on the protein levels of PHD2 and FIH1 in AC16 cells (P＜0.05), the protein level of OH-HIF-1α was decreased (P＜0.01). Conclusion BaP exposure can promote hypoxia and injury of myocardial cells and is the key PAH component of DPM that induces myocardial ischemia and hypoxia injury. BaP exposure inhibits the hydroxylation function of PHD2 on HIF-1α by combining with PHD2, decreases the level of OH-HIF-1α and induces HIF-1α accumulation. And then HIF-1α promotes anaerobic metabolism and accelerates ischemia and hypoxia injury of myocardial cells.

Safety and effectiveness of proximal aortic repair versus total arch replacement for the treatment of acute type A aortic dissection: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To evaluate the effectiveness and safety of proximal aortic repair (PAR) versus total arch replacement (TAR) for treatment of acute type A aortic dissection (ATAAD). Methods     An electronic search was conducted for clinical controlled studies on PAR versus TAR for patients with ATAAD published in Medline via PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang Database and CNKI since their inception up to April 30, 2022. The quality of each study included was assessed by 2 evaluators and the necessary data were extracted. STATA 16 software was used to perform statistical analysis of the available data. Results    A total of 28 cohort studies involving 7 923 patients with ATAAD were included in this meta-analysis, of whom 5 710 patients received PAR and 2 213 patients underwent TAR, and 96.43% of the studies (27/28) were rated as high quality. The meta-analysis results showed that: (1) patients who underwent PAR had lower incidences of 30 d mortality [RR=0.62, 95%CI (0.50, 0.77), P<0.001], in-hospital mortality [RR=0.64, 95%CI (0.54, 0.77), P<0.001], and neurologic deficiency after surgery [RR=0.84, 95%CI (0.72, 0.98), P=0.032] than those who received TAR; (2) the cardiopulmonary bypass time [WMD=–52.07, 95%CI (–74.19, –29.94), P<0.001], circulatory arrest time [WMD=–10.14, 95%CI (–15.02, –5.26), P<0.001], and operation time [WMD=–101.68, 95%CI (–178.63, –24.73), P<0.001] were significantly shorter in PAR than those in TAR; (3) there was no statistical difference in mortality after discharge, rate of over 5-year survival, renal failure after surgery and re-intervention, volume of red blood cells transfusion and fresh-frozen plasma transfusion, or hospital stay between two surgical procedures. Conclusion     Compared with TAR, PAR has a shorter operation time and lower early and in-hospital mortality, but there is no difference in long-term outcomes or complications between the two procedures for patients with ATAAD.

Clinical efficacy of sequential surgery after immune and targeted therapy in downstaging initially unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.

"Accordion" technique to promote bony union at the docking site in the treatment of tibial bone defects by Ilizarov technique / 中华创伤骨科杂志

Objective:To evaluate the effect of "accordion" technique on promoting bony union at the docking site in the treatment of tibial bone defects by bone transport.Methods:A retrospective study was conducted to analyze the data of 11 patients with tibial bone infection who had been admitted to Department of Orthopedics, The Second Hospital of Shanxi Medical University from November 2017 to February 2019. There were 10 males and 1 female with an age of (47.0±9.7) years. Seven patients were infected after internal/external fixation for open fractures and 4 cases after internal fixation for closed fractures. After surgical debridement, sensitive antibiotic bone cement was implanted, and dead or infected bone segments were radically resected. In all patients, the resulting bone defects of (6.6±2.9) cm were fixated by an Ilizarov ring external fixator and filled by bone transport. The "accordion" technique was used after the bone segments touched the docking site. The closure time, "accordion" time, bony union time and complications during bone transport were recorded.Results:None of the patients underwent bone grafting. This case series was followed up for (2.7±0.5) years. The closure time was (30.8±6.8) weeks, the "accordion" time (43.1±8.4) days, and the bony union time (31.6±9.0) weeks. None of the patients had obvious pain. Ankle stiffness was observed in 3 patients and traumatic equinus deformity in 1 patient.Conclusions:The "accordion" technique based on the Illizarov technique can accelerate mineralization of the bone segments transported, promote the bony union at the docking site, and effectively solve the problem of tibial bone defects without surgical bone grafting.

Regulatory effects of bio-intensity electric field on transformation of human skin fibroblasts / 中华烧伤杂志

Objective: To investigate the regulatory effects of bio-intensity electric field on the transformation of human skin fibroblasts (HSFs). Methods: The experimental research methods were used. HSFs were collected and divided into 200 mV/mm electric field group treated with 200 mV/mm electric field for 6 h and simulated electric field group placed in the electric field device without electricity for 6 h. Changes in morphology and arrangement of cells were observed in the living cell workstation; the number of cells at 0 and 6 h of treatment was recorded, and the rate of change in cell number was calculated; the direction of cell movement, movement velocity, and trajectory velocity within 3 h were observed and calculated (the number of samples was 34 in the simulated electric field group and 30 in 200 mV/mm electric field group in the aforementioned experiments); the protein expression of α-smooth muscle actin (α-SMA) in cells after 3 h of treatment was detected by immunofluorescence method (the number of sample was 3). HSFs were collected and divided into simulated electric field group placed in the electric field device without electricity for 3 h, and 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group which were treated with electric fields of corresponding intensities for 3 h. Besides, HSFs were divided into simulated electric field group placed in the electric field device without electricity for 6 h, and electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group treated with 200 mV/mm electric field for corresponding time. The protein expressions of α-SMA and proliferating cell nuclear antigen (PCNA) were detected by Western blotting (the number of sample was 3). Data were statistically analyzed with Mann-Whitney U test, one-way analysis of variance, independent sample t test, and least significant difference test. Results: After 6 h of treatment, compared with that in simulated electric field group, the cells in 200 mV/mm electric field group were elongated in shape and locally adhered; the cells in simulated electric field group were randomly arranged, while the cells in 200 mV/mm electric field group were arranged in a regular longitudinal direction; the change rates in the number of cells in the two groups were similar (P>0.05). Within 3 h of treatment, the cells in 200 mV/mm electric field group had an obvious tendency to move toward the positive electrode, and the cells in simulated electric field group moved around the origin; compared with those in simulated electric field group, the movement velocity and trajectory velocity of the cells in 200 mV/mm electric field group were increased significantly (with Z values of -5.33 and -5.41, respectively, P<0.01), and the directionality was significantly enhanced (Z=-4.39, P<0.01). After 3 h of treatment, the protein expression of α-SMA of cells in 200 mV/mm electric field group was significantly higher than that in simulated electric field group (t=-9.81, P<0.01). After 3 h of treatment, the protein expressions of α-SMA of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group were 1.195±0.057, 1.606±0.041, and 1.616±0.039, respectively, which were significantly more than 0.649±0.028 in simulated electric field group (P<0.01). Compared with that in 100 mV/mm electric field group, the protein expressions of α-SMA of cells in 200 mV/mm electric field group and 400 mV/mm electric field group were significantly increased (P<0.01). The protein expressions of α-SMA of cells in electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group were 0.730±0.032, 1.561±0.031, and 1.553±0.045, respectively, significantly more than 0.464±0.020 in simulated electric field group (P<0.01). Compared with that in electric field treatment 1 h group, the protein expressions of α-SMA in electric field treatment 3 h group and electric field treatment 6 h group were significantly increased (P<0.01). After 3 h of treatment, compared with that in simulated electric field group, the protein expressions of PCNA of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group were significantly decreased (P<0.05 or P<0.01); compared with that in 100 mV/mm electric field group, the protein expressions of PCNA of cells in 200 mV/mm electric field group and 400 mV/mm electric field group were significantly decreased (P<0.05 or P<0.01); compared with that in 200 mV/mm electric field group, the protein expression of PCNA of cells in 400 mV/mm electric field group was significantly decreased (P<0.01). Compared with that in simulated electric field group, the protein expressions of PCNA of cells in electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group were significantly decreased (P<0.01); compared with that in electric field treatment 1 h group, the protein expressions of PCNA of cells in electric field treatment 3 h group and electric field treatment 6 h group were significantly decreased (P<0.05 or P<0.01); compared with that in electric field treatment 3 h group, the protein expression of PCNA of cells in electric field treatment 6 h group was significantly decreased (P<0.01). Conclusions: The bio-intensity electric field can induce the migration of HSFs and promote the transformation of fibroblasts to myofibroblasts, and the transformation displays certain dependence on the time and intensity of electric field.

Safety and efficacy of a treatment protocol in converting initially unresectable to resectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors (ICIs) and antiangiogenic targeted drugs (AATDs) in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma (HCC).Methods:The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed. There were 34 males and 7 females, aged (51.8±10.7) years. The clinical characteristics, conversion to resectable HCC, adverse drug reactions, surgical data and postoperative complications were analysed. Patients were followed-up by outpatients clinics or telephone calls.Results:There were 5 patients with Chinese Liver Cancer Staging (CNLC)-Ⅰb, 4 with CNLC-Ⅱ, 28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol. Among them, 28 patients had portal vein tumor thrombosis (PVTT) and 4 had retroperitoneal lymph node metastases. All patients had a mean tumor diameter of (9.16±4.43) cm before and (6.49±4.69) cm after the treatment protocol. The latter was based on the last assessment before hepatectomy. The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles (median dose cycles, 5) of protocal therapy: 15 patients achieved a complete response; 15 patients achieved a partial response; 6 patients had a stable disease, and 5 patients had a progressive disease. 21 patients (51.2%) experienced adverse reactions associated with drug treatment, which resolved with symptomatic treatment or brief discontinuation of the therapy. All patients underwent successful hepatectomy. Postoperative complications of grade Ⅱ or higher occurred in 9 patients (22.0%). The cumulative overall survival rates at 6 months, 1 year and 2 years from diagnosis were 100.0%, 92.6% and 64.7% respectively. The cumulative overall survival rates at 6 months, 1 year and 2 years after surgery were 95.1%, 74.7% and 60.8%, and the recurrence-free survival rates at 6 months, 1 year and 2 years after surgery were 87.8%, 56.7% and 48.6%, respectively.Conclusions:This study provided preliminary evidences that surgical resection after immunotherapy combined with targeted therapy in patients with initially unresectable HCC was safe and efficacious.

Analysis of the risk factors of postoperative delirium in the elderly hip fracture patients / 中华老年医学杂志

Objective:To analyze the risk factor of postoperative delirium in the elderly hip fracture patients.Methods:A total of 1051 patients with hip fracture aged 60 years and over, admitted to Beijing Hospital from January 2010 to December 2017 were retrospectively analyzed.They were divided into a postoperative delirium group(n=156)with 56 males and 100 females, 81 femoral neck fractures and 75 intertrochanteric fractures, and the control group(n=895)with no delirium, receiving the corresponding treatment in the same period.The complications, laboratory tests, fracture types, operation methods, the time from fracture to operation, operation time, intraoperative blood loss, intraoperative blood transfusion were compared between the two groups.Risk factors of postoperative delirium in the elderly hip fracture patients were screened using the binary multi-factor logistic regression analysis.Results:Of the 1 051 patients, 156 cases(14.8%)delirium occurred.There was no significant difference in fracture type and operation methods( P>0.05)between the 2 groups.The age was significantly older in the observation group(82.9±6.6)years than in the control group(79.9±7.2)years.The serum albumin before operation(37.1±2.9)g/L, creatinine clearance rate(52.4±22.2)ml·min -1·(1.73 m 2) -1in the observation group were significantly lower than in the control group[(37.8±3.8)g/L, (59.0±30.0)ml·min -1·(1.73 m 2) -1]( P<0.05). The past dementia rate was higher in delirium group[19.8%(31 cases)]than in control group[2.2%(20 cases)], with statistically significant difference( χ2=89.503, P<0.01). The proportion of patients with more than two medical diseases was higher in delirium group[51.9%(81 cases)]than in control group[40.3%(361)]( χ2=7.320, P<0.01). There were no significant differences(all P>0.05)between.the two groups in hemoglobin, white blood cell, serum K and Na, American Society of Anesthesiologists(ASA)grade, and the incidences of Parkinson's disease, pulmonary diseases and cardiovascular diseases(all P>0.05). The binary multi-factor Logistic regression analysis showed that the age, past dementia and kidney dysfunction were the risk factors for the postoperative delirium in the elderly hip fracture patients(all P>0.05). Conclusions:The incidence of postoperative delirium in the elderly hip fractures patients is high.Age, past dementia and kidney dysfunction are the risk factors for postoperative delirium in the elderly hip fracture patients, which should be prevented and improved preoperatively.

Clinical characteristics and prognostic analysis of hip fractures in patients aged 90 and over / 中华老年医学杂志

Objective:To investigate the clinical characteristics and prognosis of hip fractures in patients aged 90 and over.Methods:Clinical data of hip fracture patients aged 90 years and older admitted to Beijing Hospital from January 2016 to June 2020 were retrospectively analyzed.Patients were divided into a surgical treatment group and a conservative treatment group according to treatment received.Mortality and walking function 30 days and 1 year after injury were followed up.The mortality and walking function 1 year after injury in the two groups of patients were compared and analyzed, and related factors affecting the 1-year mortality rate of the surgical treatment group were analyzed.Results:Eventually 114 cases were included, with 18 in the conservative treatment group and 96 in the surgical treatment group.There were no significant differences in age, sex, American Society of Anesthesiologists(ASA)score, comorbidities, fracture type, hemoglobin, total protein, albumin and coagulation function at admission, walking ability before injury, and length of stay between the two groups(all P>0.05). Of the 18 conservatively treated patients, 9 died within 1 year(50.0%). Among 96 surgically treated patients, 20 died within 1 year(20.8%). The difference between the two groups was statistically significant( χ2=6.789, P=0.016). Among the 9 patients who survived 1 year after injury under conservative treatment, 1(11.1%)was able to walk independently, 2(22.2%)were able to walk with a walker, and 6(66.7%)were unable to walk; Among the 76 surviving patients 1 year after injury under surgical treatment, 16(21.1%)were able to walk independently, 50(65.8%)were able to walk with a walker, and 10(13.1%)were unable to walk.There was a statistically significant difference in walking ability between the two groups( χ2=20.030, P<0.001). Univariate analysis results showed that ASA score, walking ability before injury and total protein were correlated with 1-year mortality after injury( χ2 or t=5.803, -2.176, 29.400, all P<0.05). Multivariate logistic regression results showed that the inability to walk independently before injury was an independent risk factor for death within 1 year after injury[ HR(95% CI)=15.95(4.42-57.55), P<0.001]. Conclusions:The prognosis of surgical treatment of hip fractures in patients aged 90 and over is better than that of conservative treatment.The inability to walk independently before injury is an independent risk factor for death within 1 year after injury.

Epidemiological characteristics analysis of hip fractures in the elderly / 中华老年医学杂志

Objective:To analyze the epidemiological characteristics of geriatric hip fractures.Methods:This study retrospectively analyzed the clinical characteristics of 2 054 elderly patients with hip fracture aged 60 years and over who were admitted to Beijing Hospital from January 2011 to December 2020.The epidemiological characteristics of geriatric hip fractures were analyzed from the aspects of age, gender, fracture type, length of stay, surgical method and surgical complications.Results:The total number of hip fractures patients admitted from 2011 to 2020 showed a general upward trend in quantity.Among them, there were 1 177 femoral neck fractures(57.3%, 1 177/2 054), and 877 intertrochanteric femoral fractures(42.7%, 877/2 054)with statistical differences in the distribution of fracture types between patients at different ages( χ2=61.727, P<0.001). A total of 1 839 patients chose surgical treatment, accounting for 89.5% of the total number of patients.Artificial femoral head arthroplasty was the most common operation mode for patients with femoral neck fractures(783 cases, 75.4%).534 patients with intertrochanteric femoral fractures(66.8%)were treated with closed reduction and femoral intramedullary nailing.There was a statistically significant difference in operation modes among different fracture types( χ2=1 480.800, P<0.001). The length of hospital stay in patients with femoral neck fracture was(14.2±8.3)days, which was significantly longer than in patients with femoral neck fracture(13.2±10.9)days( t=2.417, P=0.016). There was no significant difference in the time from admission to operation between the two groups[(5.7±3.5)days vs.(5.4±3.3)days]( t=1.954, P=0.051). Among all the comorbidities of hip fracture patients, the top 5 diseases were cardiovascular system diseases(2 001 cases, 97.4%), nervous system diseases(1 105 cases, 53.8%), endocrine system diseases(814 cases, 39.6%), skeletal and muscular system diseases(623 cases, 30.3%), digestive system diseases(472 cases, 23.0%).1 485 patients(72.3%)had 3 or more comorbidities. Conclusions:Hip fractures in the elderly have some epidemiological distribution characteristics in terms of age, gender, length of hospitalization, injury mechanism and comorbidities, which is conducive to further improve the prevention and treatment strategies for hip fractures and promote the rational allocation of medical resources.

Experimental study of dopamine ameliorating the inflammatory damage of olfactory bulb in mice with allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.

Sesquiterpene lactones of Aucklandia lappa: Pharmacology, pharmacokinetics, toxicity, and structure–activity relationship / 中草药·英文版

The medicinal part of Aucklandia lappa (Asteraceae) is its dried root, which is one of the commonly used Chinese medicinal materials. Here we reviewed sesquiterpene lactones isolated from A. lappa over the past ten years in the following aspects of pharmacological activities, pharmacokinetics, toxicology, structure–activity relationship. Pharmacological activities consist of anti-cancer, anti-inflammatory activity, anti-immunity activity, anti-oxidant activity, antimicrobial activity, spasmolytic activity and so on. The extractive, showing similar pharmacokinetics parameters, may exert their various biological activities by the interaction of their α-methylene-γ-butyrolactone moiety with the thiol groups of biomacromolecules through Michael-addition. However, the poor aqueous solubility, non-selective binding as a Michael acceptor at undesired targets limited clinical translation of this class. In order to evaluate the potential effect of the extractive applied in clinical trial, the present review outlines information on pharmacological activities, pharmacokinetics, toxicology, and structure–activity relationship, as well as the future research directions of the extractive for further development and utilization of A. lappa.

The expression and significance of TRPM8 among chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To compare the expression and difference of melastatin-related transient receptor potential 8(TRPM8) among chronic rhinosinusitis, nasal polyps and normal mucosa tissues. And to explore the significant expression of TRPM8 among CRSwNP. Methods: Fifty-one patients underwent endoscopic sinus surgery in the Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from February 2019 to January 2020 were recruited, including 33 males and 18 females, aged from 14 to 65 years old (34.55±1.689).Immunohistochemistry was used to detected the expression of TRPM8 protein among CRSsNP(17),CRSwNP (17) and control tissuses(17). In addition, the correlation between the expression of TRPM8 protein in CRSwNP patients and preoperative CT Lund-Mackay scores and preoperative VAS scores and sinonasal outcome test-20 scores was analyzed, respectively. The primary human nasal epithelial cells were cultured in vitro and the expression of TRPM8 was detected by quantitative real-time PCR and western blotting . The tissue in control group, chronic rhinosinusitis without nasal polyps (CRSsNP) group and the CRSwNP group were collected and grinded into tissue homogenized. The expression of TRPM8 protein was detected by western blotting after 24 h stimulation after homogenate was added into the medium of RPMI 2650 and primary nasal epithelial cells. Results: Compared with the control, the expression of TRPM8 was significantly up-regulated in nasal polyps (t=6.852, P<0.05). TRPM8 was mainly expressed in epithelial cells. The expression of TRPM8 in the epithelial cells of CRSsNP had no difference with the control group (t=1.980, P>0.05). In addition, the expression of TRPM8 in CRSwNP patients was positively correlated with the preoperative CT Lund-Mackay scores and VAS scores and SNOT-20 scores (r=0.512, P<0.05;r=0.853, P<0.01;r=0.814, P<0.01). After cultured primary epithelial cells in vitro, the expression level of TRPM8 in epithelial cells derived from nasal polyp was significantly higher than that in control group (t=8.845, P<0.05). By adding the homogenization of control and CRSsNP and CRSwNP tissues, the expression of TRPM8 in RPMI 2650 cells and primary nasal epithelial cells was changed and that was significantly increased after adding the homogenization of the group of CRSwNP. Conclusion: TRPM8 is highly expressed in nasal polyps epithelial cells, suggesting that TRPM8 may be involved in the pathogenesis of nasal polyps regulated by nasal epithelial cells.

Stick supporting reposition used to treat irreducible intertrochanteric fractures / 中华创伤骨科杂志

Objective:To evaluate our self-designed stick supporting reposition which was used to treat irreducible intertrochanteric fractures.Methods:A retrospective study was conducted of the 138 patients with irreducible intertrochanteric fracture (an observational group) who had been treated by stick supporting reposition followed by intramedullary nailing at Department of Orthopaedics, Beijing Hospital between April 2015 and December 2019. They were 45 males and 93 females with an age of (79.9±8.2) years; by AO classification, there were 25 cases of type 31-A1, 98 cases of type 31-A2 and 15 cases of type 31-A3. The other 142 patients with irreducible intertrochanteric fracture were included as a control group who had been treated by open or limited open reduction and intramedullary nailing between January 2010 and March 2015. The 2 groups were compared in terms of reduction time, operation time, intraoperative blood loss, reduction quality, fracture union time and complications.Results:The 2 groups were comparable because there was no significant difference between them in preoperative general data or follow-up time ( P>0.05). The reduction time [(12.0±3.4) min], operation time [(64.1±6.5) min], and intraoperative blood loss [(228.0±40.0) mL] in the observational group were significantly less than those in the control group [(18.3±8.9) min, (72.3±11.2) min and (319.1±95.0) mL] ( P<0.05). The reduction quality in the observational group (82 excellent and 56 acceptable cases) was significantly better than that in the control group (63 excellent, 65 acceptable and 14 poor cases) ( P<0.05). The fracture union time for the observational group [(3.8±0.9) months] was significantly shorter than that for the control group [(4.0±0.9) months] ( P>0.05). There were 6 cases of internal fixation failure and 8 cases of hip varus deformity in the control group, but no such complications occurred in the observational group. Conclusion:In the treatment of irreducible intertrochanteric fractures, compared with open or limited open reduction, our stick supporting reposition may shorten operation time, reduce intraoperative blood loss and improve quality of fracture reduction.

Curve evolution during bracing in children with scoliosis secondary to early-onset neurofibromatosis type 1: indicators of rapid curve progression / 中华医学杂志(英文版)

BACKGROUND@#Scoliosis secondary to neurofibromatosis type 1 (NF1) in children aged 10°/year) were identified. The age at modulation and the AV before and after modulation were obtained. Patients with (n = 18) and without rapid curve progression (n = 10) were statistically compared.@*RESULTS@#Twenty-eight patients with a mean age of 6.5 ± 1.9 years at the initial visit were reviewed. The mean Cobb angle of the main curve was 41.7° ± 2.4° at the initial visit and increased to 67.1° ± 8.6° during a mean follow-up of 44.1 ± 8.5 months. The overall AV was 6.6° ± 2.4°/year for all patients. At the last follow-up, all patients presented curve progression of >5°, and 20 (71%) patients had progressed by >20°. Rapid curve progression was observed in 18 (64%) patients and was associated with younger age at the initial visit and a higher incidence of modulation change during follow-up (t = 2.868, P = 0.008 and 10°/year is associated with younger age at the initial visit, and modulation change indicated the occurrence of the rapid curve progression phase.

Advances on the combined immunotherapy for advanced unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Recently, the clinical trials of combined immunotherapy for advanced hepatocellular were completed successfully (Imbrave150, Keynote524), which have significantly increased the objective response rate and prolonged median overall survival time. The success of combined immunotherapy provides great potential and reality for subsequent surgical intervention of advanced hepatocellular carcinoma. Nowadays, the hot topics of combined immunotherapy include the choices of combined immunotherapy, the perioperative period determination, tumor immune microenvironment, and effective biomarkers of immunotherapy selection, and so on. This paper intends to summarize the above-related issues.

Ineffective treatment technique of convex epiphysiodesis for congenital scoliosis / 中国骨伤

OBJECTIVE@#To discuss the long-term outcome of convex epiphysiodesis in the treatment for congenital scoliosis (CS).@*METHODS@#The clinical data of 22 patients with hemivertebral deformity undergoing convex epiphysiodesis from the October 1998 to Febuary 2008 were respectively analyzed. There were 12 males and 10 females. The whole spine anteroposterior radiographs were taken preoperatively, at 3-month postoperatively and at the final follow-up to measure the main curve and the compensatory curve. The progression rate was calculated for each patient. Observing the correlation between the progression rate and annual progression of the scoliosis and age, gender, hemivertebral number, hemivertebral position, preoperative main curve Cobb angle and compensatory curve Cobb angle, comparing different ages, genders, hemivertebral number and position, and preoperative main curve Cobb angle on the progression of postoperative curve.@*RESULTS@#The mean Cobb angle of main curve changed from (40.5±9.8) ° before surgery to (39.5±11.1) ° at 3 months after surgery, which significantly increased to (46.8±13.9) ° in the final follow-up. Meanwhile the mean Cobb angle of compensatory curve was changed from (20.1±10.8) ° before surgery to (23.0±11.1) °, which significantly increased to (29.9±11.5) ° in the final follow-up. There were no significant differences in the Cobb angle of the main curve and the compensatory curve between postoperative 3 months and before operation (>0.05). The difference between the final follow-up and the preoperative, postoperative 3 months was statistically significant (<0.01). Twenty patients experienced progression of both main curve and compensatory curve, with a mean progression rate of (19.2±17.9)% for main curve and (39.6±37.0)% for compensatory curve. The annual progression volume was (1.5± 1.4) ° for main curve and (1.4±1.3) ° for compensatory curve. Three patients underwent lateral convex orthopedic internal fixation due to postoperative scoliosis progression. The curve progression was significantly correlated with age at the time of surgery and hemivertebral number. There was a significant correlation between the age of the operation, the main curve angle, the preoperative compensatory curve angle and the annual progression volume of the main curve (<0.05).@*CONCLUSION@#The convex epiphysiodesis technique cannot effectively prevent curve progression of CS patients in the long-term follow-up. It is not recommended to apply this technique to the treatment of patients with congenital hemivertebrae.

Establishment of electrical immunosensor for the detection of nuclear matrix protein-22 / 中华检验医学杂志

Objective@#A label-free electrochemical immunosensor was developed for the detection of nuclear matrix protein-22 (NMP22) as a biomarker of bladder cancer.@*Methods@#The study was based on the establishment and validation of the methodology. Urine samples were collected from 20 patients with bladder cancer and 20 controls in the affiliated Hongqi hospital of Mudanjiang medical university from September in 2017 to July in 2019 to validate the developed method. A screen-printed electrode (SPE) was modified with a film of a composite made from the reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) immobilized Zn-based-Metal-organic frameworks deposited with Au nanoparticles (rGO-TEPA@Au-ZIF8). Primary antibody against NMP22 was immobilized on the Au nanoparticles on the surface of the modified SPE, which then was blocked with bovine serum albumin to elimiate nonspecific binding sites. The process of the construction of the proposed sensorwas characterized by cyclic voltammetry and electrochemical impedance spectroscopy. Differential pulse voltammetry was used to evaluate the linear range, recovery, precision, selectivity and stability. The data were analyzed by Mann-Whitney U test.@*Results@#Under optimal conditions, the immunosensor exhibited a linear range of 0.01-1000 ng/mlwith a detection limit of 3.33 pg/ml (S/N=3) and a standard recovery of 97.65%-107.05%. The levels of NMP22 in urine samples from patients with bladder cancer [66.03 (4.34, 91.74)]ng/ml determined by the proposed sensor were significantly higher than those of controls 0.54(0.06, 8.84) ng/ml(P=0.001).@*Conclusion@#The immunosensor can achieve sensitive, rapid and acucurate detection of NMP22, and has potential application prospects in monitoring tumor markers.

Establishment of electrical immunosensor for the detection of nuclear matrix protein-22 / 中华检验医学杂志

Objective A label-free electrochemical immunosensor was developed for the detection of nuclear matrix protein-22 (NMP22) as a biomarker of bladder cancer. Methods The study was based on the establishment and validation of the methodology. Urine samples were collected from 20 patients with bladder cancer and 20 controls in the affiliated Hongqi hospital of Mudanjiang medical university from September in 2017 to July in 2019 to validate the developed method. A screen-printed electrode (SPE) was modified with a film of a composite made from the reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) immobilized Zn-based-Metal-organic frameworks deposited with Au nanoparticles (rGO-TEPA@Au-ZIF8). Primary antibody against NMP22 was immobilized on the Au nanoparticles on the surface of the modified SPE, which then was blocked with bovine serum albumin to elimiate nonspecific binding sites. The process of the construction of the proposed sensorwas characterized by cyclic voltammetry and electrochemical impedance spectroscopy. Differential pulse voltammetry was used to evaluate the linear range, recovery, precision, selectivity and stability. The data were analyzed by Mann-Whitney U test. Results Under optimal conditions, the immunosensor exhibited a linear range of 0.01-1000 ng/mlwith a detection limit of 3.33 pg/ml (S/N=3) and a standard recovery of 97.65％-107.05％. The levels of NMP22 in urine samples from patients with bladder cancer [66.03 (4.34, 91.74)]ng/ml determined by the proposed sensor were significantly higher than those of controls 0.54(0.06, 8.84) ng/ml(P=0.001). Conclusion The immunosensor can achieve sensitive, rapid and acucurate detection of NMP22, and has potential application prospects in monitoring tumor markers.