[Investigation of the immune profile of multiple myeloma patients achieving long-term survival after autologous stem cell transplantation].

Objective: To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients. Methods: In the follow-up cohort of patients with newly diagnosed MM and who received "novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy" in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results: The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions: The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

[Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma].

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

[Clinical application of flexible bronchoscopy in the treatment of airway foreign body].

Airway foreign body is the unintentional entry of objects into the larynx, trachea, or bronchi, causing airway obstruction, severe coughing, wheezing, breathing difficulties, or even asphyxiation. It is a common emergency condition in respiratory, critical care, emergency, otolaryngology, and pediatric departments, etc. With the popularization of flexible bronchoscopic techniques, endoscopic foreign body removal has been widely used in adults and children. The combined application of various instruments, such as alligator forceps, mesh baskets, balloons, and cryoprobes could safely and effectively remove foreign body. This article briefly described the treatment modalities for airway foreign body and summarized effective approaches using flexible bronchoscopy in its treatment.

Magnetically Hidden State on the Ground Floor of the Magnetic Devil's Staircase.

We investigated the low-temperature and high-field thermodynamic and ultrasonic properties of SrCu_{2}(BO_{3})_{2}, which exhibits various plateaux in its magnetization curve above 27 T, called a magnetic Devil's staircase. The results of the present study confirm that magnetic crystallization, the first step of the staircase, occurs above 27 T as a first-order transition accompanied by a sharp singularity in heat capacity C_{p} and a kink in the elastic constant. In addition, we observe a thermodynamic anomaly at lower fields around 26 T, which has not been previously detected by any magnetic probes. At low temperatures, this magnetically hidden state has a large entropy and does not exhibit Schottky-type gapped behavior, which suggests the existence of low-energy collective excitations. Based on our observations and theoretical predictions, we propose that magnetic quadrupoles form a spin-nematic state around 26 T as a hidden state on the ground floor of the magnetic Devil's staircase.

[Clinical application and progress of airway stent in subglottic stenosis].

Laryngotracheal stenosis is caused by various reasons of laryngotracheal cartilage stent malformation, collapse or defect, laryngotracheal mucosa scar formation or submucosal tissue hyperplasia, eventually resulting in dyspnea. Subglottic stenosis refers to the airway stenosis from subglottic to the lower margin of the cricoid cartilage, which is a special type of laryngotracheal stenosis. The most common cause is iatrogenic injury, such as prolonged tracheal intubation and tracheotomy. Currently, the main treatments include surgical treatment, tracheostomy, endoscope-guided stent implantation and drug therapy. As for the patients who have dyspnea not suitable for surgery or in urgent need of preoperative transitional treatment, stent implantation guided by respiratory endoscopy has become an important treatment. In this paper, we reviewed 51 literatures on stent implantation of subglottic stenosis since 1994 retrieved from PubMed, CBM, CNIT, Wan-fang and VIP databases, focusing on the comparison of the efficacy, complications and prognosis of metal stent, hourglass-shaped DUMON stent, straight-type DUMON stent and Montgomery T tube and investigated the clinical application of endoscope-guided stent implantation in subglottic airway stenosis. Literature studies have shown that compared with DUMON silicone stents and metal stents, T tube has more significant advantages, higher treatment success rate and lower complication rate. Therefore, Montgomery T tube is more suitable for long-term treatment of patients with subglottic stenosis. With the improvement and update of new technology and materials, the vigorous development of new airway stents also provides a new stent treatment mode with better histocompatibility, fewer complications and customized options for the patients with subglottic stenosis.

[Effectiveness and safety of robotic assisted-bronchoscopy system in locating and removing spring coils placed in the peripheral lung of beagle dogs: a pilot study].

Objective: To evaluate the effectiveness and safety of the robotic assisted bronchoscope system for localizing and removing the spring coils that placed in the peripheral lung of beagle dogs. Methods: The study was conducted from June 18th to June 20th, 2021. Metallic lung coils were placed as the simulated lesions to the periphery of the lungs of two adult male beagle dogs using a bronchoscope under general anesthesia. The navigation path was planned by the navigation function that built in the robotic bronchoscope system. After training, the doctors operated the robotic bronchoscope system to locate and remove the coils from the lung. The navigation success rate, sampling success rate, position of the coil, navigation time, sampling time, and operation time were evaluated. The damage to the airway mucosa during the operation and the vital signs of the beagles during and post-operation were accessed. Chest computerized tomography (CT) was performed post-operation to detect if there were complications such as pneumothorax and bleeding. Results: A total of 12 spring coils were successfully inserted into the two beagles. All the navigation paths of the simulated lesions were successfully planned. The navigation success rate was 12/12. The navigation time was (43.9±19.8) seconds. The distance between the tip of the flexible endoscope arm and the target point measured by the navigation system was (6.93±2.15) mm. The locations of the simulated lesions were distributed in the 6th-8th generation of bronchi. The sampling success rate was 12/12. The sampling time was (42.4±11.3) seconds. There was no pneumothorax or mediastinal emphysema after the placement of the coil. The vital signs of the beagle dogs were stable throughout the operation, and no operation-related or postoperative complications occurred. Conclusions: The robotic bronchoscope system can be used to locate and remove the spring coils from the peripheral lung of beagle dogs, and the procedure is simple and safe. It suggests that the robotic bronchoscopy system has great clinical significance in the sampling and diagnosis of peripheral lung lesions.

Phenotypical and potential functional characteristics of different immune cells expressing CD28H/B7-H5 and their relationship with cancer prognosis.

CD28H and B7-H5 have been identified as receptor-ligand pairs in the B7/CD28 family, and have co-stimulatory activity in immune cells. Here, we have systematically reviewed the research reports concerning the CD28H/B7-H5 pathway. It was found that CD28H is mainly expressed in T cells and natural killer (NK) cells with naive and poorly differentiated properties, and repeated antigen stimulation leads to permanent loss of CD28H. In tumors, CD28H is mainly expressed in tissue-resident memory (TRM ) lymphocyte T cells, which is associated with improved tumor prognosis. B7-H5 is a ligand for CD28H and is widely expressed in tumor cells. B7-H5 expression is closely related to the prognosis of the tumor. Studies have shown that high expression of B7-H5 in tumor is related to a worse prognosis for lung cancer, osteosarcoma, oral squamous cell carcinoma (OSCC), breast carcinoma, human clear cell renal cell carcinoma (ccRCC), intrahepatic cholangiocarcinoma (ICC), bladder urothelial carcinoma (BUC) and colorectal cancer (CRC), but is associated with a better prognosis for pancreatic ductal adenocarcinoma (PDAC) and glioma. Controversial views exist in studies on gastric cancer prognosis.

Prognostic model for identifying candidates for hepatectomy among patients with hepatocellular carcinoma and hepatic vein invasion.

BACKGROUND: Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection. METHODS: Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH-HVTT model with contour plot was developed using a non-linear model in the training cohort, and subsequently validated in internal and external cohorts. RESULTS: Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH-HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low- and high-risk groups with distinct long-term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus. CONCLUSION: The EHBH-HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.

ANTECEDENTES: La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes. MÉTODOS: Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH-HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas. RESULTADOS: De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH-HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente. CONCLUSIÓN: El modelo EHBH-HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.

Giant Isolated Attosecond Pulses from Two-Color Laser-Plasma Interactions.

A new regime in the interaction of a two-color (ω,2ω) laser with a nanometer-scale foil is identified, resulting in the emission of extremely intense, isolated attosecond pulses-even in the case of multicycle lasers. For foils irradiated by lasers exceeding the blow-out field strength (i.e., capable of fully separating electrons from the ion background), the addition of a second harmonic field results in the stabilization of the foil up to the blow-out intensity. This is then followed by a sharp transition to transparency that essentially occurs in a single optical cycle. During the transition cycle, a dense, nanometer-scale electron bunch is accelerated to relativistic velocities and emits a single, strong attosecond pulse with a peak intensity approaching that of the laser field.

A higher level of total bile acid in early mid-pregnancy is associated with an increased risk of gestational diabetes mellitus: a prospective cohort study in Wuhan, China.

PURPOSE: To assess the longitudinal associations between maternal total bile acid (TBA) levels during early mid-pregnancy and the subsequent risk of gestational diabetes mellitus (GDM). METHODS: In a prospective cohort study, pregnant women who were enrolled prior to gestational week 16 were followed until delivery. TBA levels were tested during weeks 14-18 of gestation. Using logistic regression, we analyzed the associations between quartiles of TBA and GDM based on a 75-g oral glucose tolerance test (OGTT) at 24-28 gestational weeks. RESULTS: The GDM rate was 7.9% (114/1441). The mean TBA level was higher in women with GDM than in those without GDM (2.1 ± 2.0 vs 1.5 ± 1.0 µmol/L, P = 0.000). The highest TBA level quartile (2.1-10.7 µmol/L) had a 1.78-fold (95% CI 1.01, 3.14) increased risk of GDM compared with that of the lowest quartile (0.0-0.8 µmol/L) after adjusting for pre-pregnancy body mass index (BMI), gestational, age at TBA test and other confounders. High TBA levels were involved in the fasting glucose level rather than that at 1 h and 2 h after OGTT in all participants. CONCLUSIONS: Pregnant women with higher serum TBA levels during early mid-pregnancy have a higher risk of developing GDM. TBA may be a new risk factor for GDM.

Downregulation of CDCA3 expression inhibits tumor formation in pancreatic cancer.

Downregulation of cell division cycle-associated 3 (CDCA3) markedly inhibited cell growth and induced apoptosis in tumors. However, the effect of CDCA3 in pancreatic cancer (PAC) was rarely investigated. Therefore, this study attempted to clarify the role of CDCA3 in PAC. The mRNA and protein expression of CDCA3 were examined in PAC cell lines and tumor tissues by using real-time quantitative PCR (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). The effects of CDCA3 downregulation on cell proliferation, apoptosis, and colony information were investigated through MTT assay, Annexin V-APC single staining cell apoptosis detection, and colony formation test. The microarray and ingenuity pathway analysis were employed to explore the potential regulatory relation. The tumor xenograft model was established for determining the effect of CDCA3 downregulation on the growth of PAC in vivo. The results showed that the expression of CDCA3 in tumor tissues was higher than that of normal tissues (p<0.05). In addition, the mRNA expression of CDCA3 was markedly increased in PANC-1 cells and SW 1990 cells when compared with human pancreatic duct epithelial (HPDE) cells (p<0.05). MTT assay showed that the cell proliferation of PANC-1 cells and SW 1990 cells was significantly inhibited after the lentivirus transfection of CDCA3 knockdown (p<0.05). Annexin V-APC apoptosis assays suggested that the apoptotic cell number was markedly increased in the shCDCA3 group compared to that in the shCtrl group in SW 1990 cells and PANC-1 cells (p<0.05). Meanwhile, the activity of caspase-3/7 was obviously elevated in the shCDCA3 group compared to the shCtrl group (p<0.05). The colony formation was notably inhibited in the shCDCA3 group relative to the shCtrl group in SW 1990 cells (p<0.05). Moreover, the tumor growth was evidently suppressed in the shCDCA3 group compared with the shCtrl group in vivo (p<0.05). These findings revealed that CDCA3 plays a crucial role in the progress of PCA by regulating cell apoptosis and proliferation, which may serve as a potential target for PAC treatment.

[Epidemic trend of COVID-19 in Chinese mainland].

Objective: In order to understand the epidemic trend of COVID-19 and evaluate the effect of prevention and control, this study aims to evaluate the epidemic dynamics of COVID-19 in Chinese mainland from January 16 to February 14, 2020. Methods: The daily number of new confirmed COVID-19 cases detected by nucleic acid was collected from the National Health Commission from January 16, 2020 to February 14, 2020. The analysis included the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in Chinese mainland was 50 031, including 37 930 in Hubei Province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei Province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion: The epidemic prevention and control measures taken by the state and governments at all levels have effectively curbed the spread of the COVID-19 epidemic in Chinese mainland.

[Jiangsu Province Coronary Artery Bypass Grafting Registry study: a report of 4 661 patients in 13 centers].

Objective: To examine the overall status of the Jiangsu Province Coronary Artery Bypass Grafting Registry database. Methods: The patients date of Jiangsu Province Coronary Artery Bypass Grafting Registry database from October 2017 to December 2019 was collected retrospectively.Risk factors, history, cardiac function (New York Heart Association class), extent of coronary artery lesion, European system for cardiac operative risk evaluation Ⅱ (EuroSCORE Ⅱ), cardiopulmonary bypss, arterial grafts, the numbers and flow of grafts and postoperative major adverse cardiac and cerebrovascular event(MACCE) information were analyzed. The clinical data of patients underwent on-pump CABG(ONCABG) or off-pump CABG (OPCAB) were compared by t test or χ(2) test. Results: Up till December 2019, the database enrolled 7 138 patients, in which 4 661 patients receiving primary isolated CABG. There were 3 486 males and 1 175 females with the age of (64.6±8.1) years (range:31 to 87 years). There were coronary left main disease in 960 patients, triple vessel disease in 3 934 patients, both left main and triple vessel disease in 837 patients, ejection fraction>50% in 3 841 patients, cardiac function class Ⅲ to Ⅳ in 1 664 patients. EuroSCORE Ⅱ was (2.3±0.7)% (range: 0.5% to 35.8%). There were 2 731 patients (58.59%) underwent ONCABG and 1 930 patients (41.41%) underwent OPCAB. There were 4 144 patients (88.91%) for whom the left internal thoracic artery was harvested. Seven centers (2 centers routinely) used left radial artery, 5 centers (3 centers routinely) used the transit time flow meter. The graft was 3.4±0.7 (range:1 to 7), the aortic crossclamp time was (65.0±20.4) minutes (range: 21 to 196 minutes), the cardiopulmonary bypass time was (90.0±24.2) minutes (range: 33 to 227 minutes). In-hospital death ocurred in 84 patients(1.80%), while re-operation in 93 patients (2.00%), myocardial infarction in 71 patients (1.52%), cerebral infarction in 33 patients (0.71%) and dialysis in 56 patients (1.20%). There were 2 936 patients prescribed with secondary prevention drugs(62.99%).Comparing with OPCAB group, ONCABG group had younger age, more female, more diabetes mellitus, more history of myocardial infarction and percutaneous transluminal coronary angioplasty, poorer cardiac function and coronary lesions, higher EuroSCORE Ⅱ, preoperatively (all P<0.05), and was associated with higher MACCE (135/2 731 vs. 71/1 930, χ(2)=4.280, P=0.039), and of more grafts, transfusion and intra-aortic balloon counterpulsation application (all P<0.05). Conclusions: Jiangsu Province Coronary Artery Bypass Grafting Registry database is generally in good operation, and some parameters still need to be improved. Comparing with OPCAB group, ONCABG has more severe preoperative general conditions, while the outcomes is acceptable.

The role of HLA variation in lymphoma aetiology and survival.

Epidemiologic and laboratory evidence has consistently supported a strong inflammatory and immune component for lymphoma aetiology. These studies have consistently implicated variation in the immune gene, human leucocyte antigen (HLA), to be associated with lymphoma risk. In this review, we summarize the historical and recent evidence of HLA in both lymphoma aetiology and survival. The recent momentum in uncovering HLA associations has been propelled by the conduct of genome-wide association studies (GWAS), which has permitted the evaluation of imputed HLA alleles in much larger sample sizes than historically feasible with allelotyping studies. Based on the culmination of smaller HLA typing studies and larger GWAS, we now recognize several HLA associations with Hodgkin (HL) and non-Hodgkin lymphomas (NHLs) and their subtypes. Although other genetic variants have also been implicated with lymphoma risk, it is notable that HLA associations have been reported in every NHL and HL subtype evaluated to date. Both HLA class I and class II alleles have been linked with NHL and HL risk. It is notable that the associations identified are largely specific to each lymphoma subtype. However, pleiotropic HLA associations have also been observed. For example, rs10484561, which is in linkage disequilibrium with HLA-DRB1*01:01˜DQA1*01:01˜DQB1*05:01, has been implicated in increased FL and DLBCL risk. Opposing HLA associations across subtypes have also been reported, such as for HLA-A*01:01 which is associated with increased risk of EBV-positive cHL but decreased risk of EBV-negative cHL and chronic lymphocytic leukaemia/small cell lymphoma. Due to extensive linkage disequilibrium and allele/haplotypic variation across race/ethnicities, identification of causal alleles/haplotypes remains challenging. Follow-up functional studies are needed to identify the specific immunological pathways responsible in the multifactorial aetiology of HL and NHL. Correlative studies linking HLA alleles with known molecular subtypes and HLA expression in the tumours are also needed. Finally, additional association studies investigating HLA diversity and lymphoma survival are also required to replicate initial associations reported to date.

Pulsed electromagnetic fields: promising treatment for osteoporosis.

Osteoporosis (OP) is considered to be a well-defined disease which results in high morbidity and mortality. In patients diagnosed with OP, low bone mass and fragile bone strength have been demonstrated to significantly increase risk of fragility fractures. To date, various anabolic and antiresorptive therapies have been applied to maintain healthy bone mass and strength. Pulsed electromagnetic fields (PEMFs) are employed to treat patients suffering from delayed fracture healing and nonunions. Although PEMFs stimulate osteoblastogenesis, suppress osteoclastogenesis, and influence the activity of bone marrow mesenchymal stem cells (BMSCs) and osteocytes, ultimately leading to retention of bone mass and strength. However, whether PEMFs could be taken into clinical use to treat OP is still unknown. Furthermore, the deeper signaling pathways underlying the way in which PEMFs influence OP remain unclear.

Reduced TRPC6 mRNA levels in the blood cells of patients with Alzheimer's disease and mild cognitive impairment.

Transient receptor potential canonical 6 (TRPC6) inhibits ß-amyloid (Aß) production. Hyperforin, the TRPC6 agonist, reduces Aß levels and improves cognitive performance in Alzheimer's disease (AD) models. However, it's unknown whether TRPC6 expression is changed in AD patients. In this case-control study, we measured TRPC6 expression levels in the peripheral blood cells of four independent AD sets from five hospitals and one mild cognitive impairment (MCI) set from a local community (229 AD, 70 MCI, 40 Parkinson disease and 359 controls from China, total n=698) using quantitative real-time PCR assay. We found a specific reduction of TRPC6 mRNA levels in four AD sets and one MCI set. The median TRPC6 mRNA levels were lower in the following: (1) combined AD patients than in age-matched controls (0.78 vs 1.73, P<0.001); (2) mild-to-moderate AD patients than in age-matched controls (0.81 vs 1.73, P<0.001); and (3) MCI patients than in age-matched controls (0.76 vs 1.72, P<0.001). In the receiver-operating characteristic curve analysis, the area under curve was 0.85 for combined AD, 0.84 for mild-to-moderate AD and 0.79 for MCI. In a subgroup of AD patients with brain Aß examination, TRPC6 was associated with standardized uptake value ratio of Pittsburgh Compound B (Spearman's r=-0.49, P=0.04) and cerebrospinal fluid Aß42 (Spearman's r=0.43, P=0.04). The TRPC6 reduction in AD patients was further confirmed in blood RNA samples from The Australian Imaging, Biomarkers and Lifestyle Flagship Study of Aging, in post-mortem brain tissues from The Netherlands Brain Bank and in induced pluripotent stem cells-derived neurons from Chinese donors. We conclude that TRPC6 mRNA levels in the blood cells are specifically reduced in AD and MCI patients, and TRPC6 might be a biomarker for the early diagnosis of AD.

Association of serum galectin-3 with risks of death and vascular events in acute ischaemic stroke patients: the role of hyperglycemia.

BACKGROUND AND PURPOSE: Whether the association between galectin-3 and stroke outcome is modified by fasting plasma glucose (FPG) is unknown. The aim was to evaluate the prognostic effect of galectin-3 amongst ischaemic stroke patients stratified by FPG. METHODS: In all, 3082 ischaemic stroke patients were included in this study and serum galectin-3 was tested at baseline. The primary outcome was a composite outcome of death and vascular events, and secondary outcomes were death, stroke recurrence and vascular events within 1 year after stroke. RESULTS: Increased galectin-3 was significantly associated with the primary outcome, stroke recurrence and vascular events in the patients with hyperglycemia but not in those with normoglycemia (P for interaction < 0.05 for all). The multivariate-adjusted hazard ratios (95% confidence intervals) were 1.72 (1.05-2.84), 2.64 (1.14-6.12) and 2.68 (1.33-5.38) for the primary outcome, stroke recurrence and vascular events, respectively. A linear association between galectin-3 and the primary outcome was observed in hyperglycemic patients (P for linearity = 0.007). CONCLUSION: Increased galectin-3 was associated with the primary outcome, stroke recurrence and vascular events within 1 year after stroke in the patients with hyperglycemia, suggesting that galectin-3 may be an important prognostic factor for ischaemic stroke patients with hyperglycemia.

[Anti-lung cancer effect of myeloid and plasmacytoid dendritic cell combined vaccines loaded with tumor cell lysates in vitro].

Objective: To investigate the feasibility of myeloid and plasmacytoid dendritic cell combined vaccines loaded with heat-treated Lewis lung cancer cell lysates for treatment of lung cancer in mice. Methods: Bone marrow cells were induced by the recombinant mouse fms-like tyrosine kinase receptor 3 ligand (rmFlt3-L) in vitro, myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) were separated by magnetic beads. The mDC, pDC, and mDC∶pDC=1∶1 were stimulated with heat-treated Lewis lung cancer cell lysates, respectively. The effects of each group on stimulating of lymphocyte proliferation and inducing of T cell to kill tumor cells in vitro were compared. The alternations of the immunophenotypes of CD80, CD86, CD40 and major histocompatibility complex Ⅱ (MHC-Ⅱ) were detected by flow cytometry. The secretion of cytokines including interlukin-12 (IL-12), interlukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Results: The lymphocyte proliferation in mice stimulated with mDC+ pDC group loaded with heat-treated Lewis lung cancer cell lysates was 10.80±0.66, significantly higher than 8.63±0.65 of mDC group and 7.10±0.46 pDC group under the same culture conditions, respectively (P<0.05). When the ratio of effector cells: target cells (E∶T) was 10∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 31.68%±2.93%, significantly higher than 17.44%±0.97% of mDC group and 10.29%±1.33% of pDC group, respectively (P<0.05). When the ratio of E∶T was 20∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 54.77%±3.28%, significantly higher than 35.25%±1.51% of mDC group and 15.52%±0.73% of pDC group, respectively (P<0.05). When the ratio of E∶T was 40∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 73.01%±0.91%, significantly higher than 51.36%±0.58% of mDC group and 22.65%±1.28% of pDC group, respectively (P<0.05). With the rate of E∶T increased, the killing rate also increased. The mean fluorescence intensities of surface molecules including CD80, CD86, CD40 and MHC-Ⅱ of mDC: pDC=1 group pulsed with heat-treated Lewis lung cancer cell lysates were higher than those of mDC group and pDC group. The IL-6 cytokine concentrations of mDC+ pDC group, mDC group and pDC group loaded with heat-treated Lewis lung cancer cell lysates were (586.67±52.52) pg/ml, (323.33±67.14) pg/ml and (166.67±16.07) pg/ml, respectively. The concentrations of IL-12 in each group were (2 568.75±119.24) pg/ml, (2 156.25±120.55) pg/ml and (672.92±31.46) pg/ml, respectively. The concentrations of TNF-α in each group were (789.33±48.08) pg/ml, (584.89±116.49) pg/ml and (291.56±40.73) pg/ml, respectively. The concentrations of IL-6, IL-12 and TNF-α secreted by mDC+ pDC group were much higher than those of mDC group and pDC group under the same culture conditions (P<0.05). Conclusions: The mDCs and pDCs combined vaccines pulsed with heat-treated Lewis lung cancer cell lysates have synergistic effects on inducing of T lymphocyte proliferation and killing tumor cells in vitro. This synergistic anti-tumor effect is related with up-regulation of co-stimulatory molecules and increased secretion of cytokines.