ical Efficacy of Early Plastic Surgery Treatment for Patients with Deep Hand Burns.

Objective: This study aims to assess the effectiveness of early plastic surgery for deep hand burns by examining variables like VAS scores, wound healing time, and excellent hand function recovery rates. Methods: A total of 130 patients with deep hand burns admitted to our hospital between January 2020 and October 2021 were enrolled in this study. They were randomly assigned to either a control group (n = 65, deferred reconstructive surgery) or an observation group (n = 65, early reconstructive surgery) using a random number table. We compared the VAS scores, wound healing time, rates of excellent hand function recovery, complications, and overall treatment efficacy between the two groups. Results: The preoperative VAS scores were comparable between the observation and control groups (P > .05). Postoperative VAS scores in the observation group were significantly lower than those in the control group at 1, 3, and 7 days following surgery (P < .05). Additionally, the observation group exhibited shorter wound healing times and higher rates of excellent hand function recovery (P < .05). The incidence of complications such as numbness, infection, and necrosis of implants was lower in the observation group compared to the control group (P < .05). The overall treatment efficacy was also significantly better in the observation group than in the control group (P < .05). Conclusions: These findings underscore the high clinical value of early surgical intervention, supporting its broader application in the treatment of deep hand burns and potentially improving patient outcomes.

The Application of Preoperative Computed Tomography Angiography and Color Ultrasound Assisted Lower Limb Perforator Flap Design in the Repair of Lower Limb Soft Tissue Defects.

Objective: The goal of this study was to explore the application effect of preoperative computed tomography (CT) angiography and color ultrasound-assisted design of lower limb perforator flaps in the repair of lower limb soft tissue defects. Repair of soft tissue defects in the lower limbs is a challenging surgical task, and accurate preoperative location of vascular structures and detailed design of the surgical plan are crucial to the success of the surgery. This study aims to improve the accuracy and effectiveness of lower limb perforator flap repair surgery by introducing CT angiography and color ultrasound technology. Methods: Sixty-four patients who underwent lower limb soft tissue defect repair with perforator flaps were enrolled at our hospital from February 2020 to February 2023. According to their admission time, they were divided into two groups: 32 patients admitted before June 31, 2022, were included in the control group, and preoperative color Doppler ultrasound was used to assist in designing the lower limb perforator flap; 32 patients admitted after June 31, 2022, were included in the study group, and preoperative CT angiography and color Doppler ultrasound were used to assist in designing the lower limb perforator flap. Specifically, we conducted detailed records and analyzes of patients' age distribution, gender ratio, and relevant medical history. This demographic information will help reveal whether there are differences in the effectiveness of preoperative CT angiography and color ultrasound-assisted lower extremity perforator flap design among different patient groups. By considering these key factors, we can more accurately assess the actual utility of new technologies in different patient groups and provide more specific guidance for clinical practice.The therapeutic effects of the two groups of patients were recorded. The differences between the preoperative CT angiography measurements and intraoperative actual measurements of the study group were compared. Clinical indicators, sensory function in the graft area, flap survival rate, flap complication rate, and donor area complication rate were compared between the two groups. The satisfaction of patients in the two groups with the recovery of the surgical area was also compared. Results: The treatment success rate of the study group was higher than that of the control group (P < .05). There was no significant difference in the preoperative CT angiography measurements (shallow branch localization, shallow branch starting diameter, shallow branch length, deep branch starting diameter) and intraoperative actual measurements of the study group (P > .05). The operation time and intraoperative blood loss of the study group were shorter than those of the control group (P < .05), and there was no significant difference in flap harvesting area and length of hospital stay between the two groups (P > .05). There was a difference in sensory function in the graft area between the two groups, with a higher proportion of S4 grade in the study group and better recovery compared to the control group (P < .05). There was no significant difference in satisfaction evaluation between the two groups (P > .05). Conclusion: Preoperative CT angiography and color ultrasound-assisted design of lower limb perforator flaps have shown significant clinical advantages in repairing lower limb soft tissue defects, improving treatment effects and surgical efficiency. In clinical practice, this technology is expected to reduce surgical complexity, shorten surgical time, reduce the risk of intraoperative bleeding, and achieve effective defect repair while maintaining or improving the patient's sensory function.However, there are some limitations to the study, such as the relatively small sample size and single-center nature. Future research can optimize the operation process of this technology, expand the scope of research, and explore its application in the repair of soft tissue defects caused by specific causes. This technology may provide more precise and effective options for personalized treatment, especially for patients who need to preserve more sensory function.

Disease duration of progression is helpful in identifying isolated bulbar palsy of amyotrophic lateral sclerosis.

BACKGROUND: Compared with typical bulbar onset amyotrophic lateral sclerosis (ALS), isolated bulbar palsy (IBP), an often under-understood variant of ALS, is characterized by symptoms confined to bulbar region for extended periods and relative preservation of limb and ventilation function. To find a cutoff value of disease duration that can distinguish IBP from typical bulbar onset ALS well, the association of survival with disease progression in bulbar onset ALS patients was analyzed. METHODS: Clinical data of bulbar onset ALS patients were collected from January 2009 to December 2013. The duration from bulbar onset to first significant limb involvement was analyzed by a cutoff point analysis with maximally selected log-rank statistics and dichotomized to categorize patient outcomes. The patients were divided into two groups, the IBP and typical bulbar onset ALS groups, according to the cutoff value. Clinical features were compared. RESULTS: 115 bulbar onset ALS patients were recruited, and the duration from bulbar onset to first significant limb involvement was associated with survival (P < 0.001). The cutoff duration was 20 months. 19 patients were identified as IBP and 96 patients as typical bulbar onset ALS using 20 months as the cutoff duration. Female was more common, limb weakness was less frequent and pure upper motor neuron (UMN) bulbar signs were more frequent in the IBP group than in the typical bulbar onset ALS group (P = 0.047; P = 0.004; P = 0.031). The median survival time of the IBP group was significantly longer than that of the typical bulbar onset ALS group (64 months and 26 months, respectively; P < 0.001). CONCLUSIONS: A cutoff duration of 20 months from bulbar onset to first significant limb involvement may be used to specifically distinguish IBP from typical bulbar onset ALS. IBP was characterized by female predominance, relative preservation of limb function, more pure UMN bulbar signs and a relatively benign prognosis.

Multinucleated polyploid cardiomyocytes undergo an enhanced adaptability to hypoxia via mitophagy.

AIMS: There is a large subpopulation of multinucleated polyploid cardiomyocytes (M*Pc CMs) in the adult mammalian heart. However, the pathophysiological significance of increased M*Pc CMs in heart disease is poorly understood. We sought to determine the pathophysiological significance of increased M*Pc CMs during hypoxia adaptation. METHODS AND RESULTS: A model of hypoxia-induced cardiomyocyte (CM) multinucleation and polyploidization was established and found to be associated with less apoptosis and less reactive oxygen species (ROS) production. Compared to mononucleated diploid CMs (1*2c CMs), tetraploid CMs (4c CMs) exhibited better mitochondria quality control via increased mitochondrial autophagy (mitophagy). RNA-seq revealed Prkaa2, the gene for AMPKα2, was the most obviously up-regulated autophagy-related gene. Knockdown of AMPKα2 increased apoptosis and ROS production and suppressed mitophagy in 4c CMs compared to 1*2c CMs. Rapamycin, an autophagy activator, alleviated the adverse effect of AMPKα2 knockdown. Furthermore, silencing PINK1 also increased apoptosis and ROS in 4c CMs and weakened the adaptive superiority of 4c CMs. Finally, AMPKα2-/- mutant mice exhibited exacerbation of apoptosis and ROS production via decreases in AMPKα2-mediated mitophagy in 4c CMs compared to 1*2c CMs during hypoxia. CONCLUSIONS: Compared to 1*2c CMs, hypoxia-induced 4c CMs exhibited enhanced mitochondria quality control and less apoptosis via AMPKα2-mediated mitophagy. These results suggest that multinucleation and polyploidization allow CM to better adapt to stress via enhanced mitophagy. In addition, activation of AMPKα2 may be a promising target for myocardial hypoxia-related diseases.

[Ventilation function disorder of flail arm syndrome].

OBJECTIVE: To study the features of ventilation function in patients with flail arm syndrome (FAS). METHODS: The clinical data of 351 patients with sporadic amyotrophic lateral sclerosis (ALS) from 2009 to 2013 were retrospectively reviewed. Among them, 329 were classical ALS and 22 were FAS. The differences of forced vital capacity (FVC) between FAS and classical ALS were analyzed. RESULTS: The percent predicted FVC (FVC% pred) values were (88.0 ± 9.5)% in FAS and (84.3 ± 16.8)% in classical ALS including 4 and 128 patients with abnormal FVC% pred (< 80%) in FAS and classical ALS, respectively. The FVC% pred levels were significantly higher in FAS subjects [(88.0 ± 9.5)%] than in classical ALS subjects of bulb [(80.0 ± 14.8)%] or those of upper limb [(80.8 ± 16.0)%] onset with duration over 12 months (All P < 0.05). The proportion of subjects with FVC% pred < 80% was statistically lower in FAS [18.2% (4/22)] than in both classical ALS of upper limb onset [42.8% (80/187); P = 0.037] and classical ALS with duration over one year [48.5% (48/99); P = 0.009]. CONCLUSIONS: Impaired ventilation function occurs less and later in FAS than that in classical ALS of upper limb onset with duration over one year, suggesting later and less requirement for non-invasive positive pressure ventilation treatment for FAS patients. Differentiation of FAS subjects from ALS helps assess prognosis and make treatment plan for these patients.

[The association between angiogenin gene variations and familial amyotrophic lateral sclerosis in Chinese Han patients].

OBJECTIVE: To investigate effect of genetic variants in angiogenin (ANG) on the susceptibility of familial amyotrophic lateral sclerosis (FALS) in Han Chinese. METHODS: Thirty-one FALS families from 2009 to 2012 were collected and ANG gene was screened in the probands using PCR and direct sequencing. RESULTS: All 31 ALS families were autosomal dominant inheritance. No mutations and single nucleotide polymorphism were detectable in ANG gene in the 31 probands. CONCLUSION: Our study suggests that ANG gene variations may be rare in Chinese Han FALS.

[Association between VAPB mutations and familial amyotrophic lateral sclerosis in Chinese patients].

OBJECTIVE: To explore the mutations of VAPB (vesicle associated membrane protein/synaptobrevin associated membrane protein B) in Chinese patients with familial amyotrophic lateral sclerosis (FALS). METHODS: The clinical data were collected from 40 FALS families from 2008 to 2011 and the mutations of VAPB gene screened in probands using polymerase chain reaction (PCR) and direct sequencing. RESULTS: All 40 ALS families were of autosomal dominant inheritance. The male-to-female ratio of probands was 1:0.7 and the average onset age (49 ± 12) years. Upper limb onset accounted for 52.5%, lower limb onset 42.5% and bulbar onset 5.0%. No mutations were detected in VAPB gene. CONCLUSION: VAPB mutations are not a common cause and ALS8 is rare in Chinese FALS.

[Association between site of onset and ventilation dysfunction in patients with amyotrophic lateral sclerosis].

OBJECTIVE: To study the association between site of onset and ventilation dysfunction in Chinese patients with amyotrophic lateral sclerosis. METHODS: The clinical data of 344 patients with sporadic amyotrophic lateral sclerosis (SALS) in Department of Neurology of Peking University Third Hospital from January 2009 to September 2013 were retrospectively reviewed. The differences of Forced Vital Capacity (FVC) between groups with distinct site of onset were analyzed. RESULTS: There were 55, 200 and 89 patients in the group with bulbar, upper limb and lower limb onset, respectively. The values of FVC were 84% ± 14%, 83% ± 17% and 88% ± 16%, and the cases of FVC < 80% were 24 (43.64%), 81 (40.50%) and 25 (28.09%) in each group. The mean value of FVC was significantly lower and the frequency of FVC< 80% statistically higher in the group with upper limb onset in comparison with the group with lower limb onset. The mean value of FVC was lower and the frequency of FVC< 80% higher in the group with bulbar onset than in the group with lower limb onset. However, the differences were not significant between the two groups. CONCLUSIONS: Compared with SALS with upper limb onset, ventilation function disorder may occur less and later in patients with lower limb onset, who may also require noninvasive positive pressure ventilation (NIPPV) less and later.

Study on the Mechanical Properties of Cast-In-Situ Phosphogypsum as Building Material for Structural Walls.

The application of cast-in-situ phosphogypsum as the wall material of building structures can greatly reduce the environmental pollution caused by phosphogypsum. Through the uniaxial compression test of cast-in-situ phosphogypsum specimens, the compressive strength of cast-in-situ phosphogypsum is determined, the constitutive relationship of the material is drawn up, and the elastic modulus and Poisson's ratio of the material are determined. The results show that when the strain of the specimen is close to the peak strain, the cast-in-situ phosphogypsum has brittle properties and rapidly fails, where the failure state is mainly splitting failure. The retarder has a great influence on the peak stress. When the content of the retarder is about 0.3%, the peak stress is 8.6 MPa and the ultimate strain is 2.54 × 10-3, while the peak stress is 2.8 MPa and the ultimate strain is 2.01 × 10-3. The three segment constitutive fitted equations reflect all the characteristics of the compression specimen. When the strength of the cast-in-situ phosphogypsum is high, the elastic modulus is also high. When the content of the retarder is about 0.3%, the elastic modulus is 5300 MPa, and when the content of retarder is far greater than 0.3%, the elastic modulus is 2000 MPa. The Poisson's ratio of material is recommended as 0.19.

Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer.

Radiation therapy (RT) is an integral part of prostate cancer treatment across all stages and risk groups. Immunotherapy using a live, attenuated, Listeria monocytogenes-based vaccines have been shown previously to be highly efficient in stimulating anti-tumor responses to impact on the growth of established tumors in different tumor models. Here, we evaluated the combination of RT and immunotherapy using Listeria monocytogenes-based vaccine (ADXS31-142) in a mouse model of prostate cancer. Mice bearing PSA-expressing TPSA23 tumor were divided to 5 groups receiving no treatment, ADXS31-142, RT (10 Gy), control Listeria vector and combination of ADXS31-142 and RT. Tumor growth curve was generated by measuring the tumor volume biweekly. Tumor tissue, spleen, and sera were harvested from each group for IFN-γ ELISpot, intracellular cytokine assay, tetramer analysis, and immunofluorescence staining. There was a significant tumor growth delay in mice that received combined ADXS31-142 and RT treatment as compared with mice of other cohorts and this combined treatment causes complete regression of their established tumors in 60 % of the mice. ELISpot and immunohistochemistry of CD8+ cytotoxic T Lymphocytes (CTL) showed a significant increase in IFN-γ production in mice with combined treatment. Tetramer analysis showed a fourfold and a greater than 16-fold increase in PSA-specific CTLs in animals receiving ADXS31-142 alone and combination treatment, respectively. A similar increase in infiltration of CTLs was observed in the tumor tissues. Combination therapy with RT and Listeria PSA vaccine causes significant tumor regression by augmenting PSA-specific immune response and it could serve as a potential treatment regimen for prostate cancer.

Differentiating Slowly Progressive Subtype of Lower Limb Onset ALS From Typical ALS Depends on the Time of Disease Progression and Phenotype.

Background: Flail leg syndrome (FLS) is a regional variant of amyotrophic lateral sclerosis (ALS) with the characteristics of slow progression and the symptoms confined to the lumbosacral region for extended periods. However, FLS may not be easily differentiated from typical ALS. Objective: The objective of the study was to determine a cutoff time of disease progression that could differentiate FLS from the typical lower limb onset ALS. Methods: A cutoff point analysis was performed with maximally selected log-rank statistics in patients with lower limb onset ALS registered from 2009 to 2013. Based on the cutoff duration from the lower limb onset to second region significantly involved (SRSI), all patients were divided into the slowly progressive subtype of lower limb onset ALS group and the typical lower limb-onset ALS group. Patients with the slowly progressive subtype of the lower limb onset ALS, who had the flail leg phenotype, were classified as patients with FLS. Differences between groups were analyzed. Results: Among the 196 patients recruited, 157 patients with a duration <14 months from lower limb onset to SRSI were classified as having typical lower limb onset ALS. Twenty-nine patients with a duration more than or equal to 14 months and the flail leg phenotype were classified as having FLS. Patients with FLS exhibited a median diagnostic delay of 25 months, a median duration of 24 months from lower limb onset to SRSI, a forced vital capacity abnormity rate of 12.5% at the first visit to our department, and a median survival time of 80 months, which were significantly different from those of patients with typical lower limb onset ALS (p < 0.001, p < 0.001, p = 0.024, p < 0.001). The 5-year survival rate of the FLS group (79.3%) was much higher than that of the other group (1.9%). Conclusions: A crucial feature in differentiating FLS from typical lower limb onset ALS in Chinese patients may be symptoms confined to the lumbosacral region for at least 14 months, which may be better than 12 or 24 months used in the previous studies. The FLS was characterized by slower progression, less and later respiratory dysfunction, and a more benign prognosis than the typical lower limb onset ALS.

The Clinical Features of In-Hospital Recurrence in Acute Ischaemic Stroke Patients over Time: A Real-World Observation at a Single Center.

Acute ischaemic stroke (AIS) has a high risk of recurrence, particularly in the early stage. Our study aimed to assess the clinical characteristics and risk factors of in-hospital ischaemic recurrence in AIS patients in different periods. This study was a retrospective, single-center analysis. The patients were divided into two stages based on their admission time. The primary endpoint was recurrent stroke during hospitalization. In total, 978 patients in Stage 1 and 1047 patients in Stage 2 were included in this study. The in-hospital recurrence rate in Stage 1 was 5.9%, while that in Stage 2 was 4.0% (p = 0.046). A recurrence rate reduction mainly occurred in the minor stroke and large-artery atherosclerosis (LAA) stroke patients. Infection was an independent risk factor despite amelioration by antiplatelet therapy (p < 0.001). Diabetes patients also had a higher risk of in-hospital ischaemic recurrence among the minor stroke and large-artery atherosclerosis patients. A positive attitude towards antiplatelet therapy failed to completely halt recurrence of the disease. In conclusion, the rate of in-hospital ischaemic recurrence in AIS patients showed a decreasing trend over time, especially in the minor stroke and large-artery atherosclerosis stroke patients. Infection and diabetes were associated with a higher risk of stroke recurrence.

Immune modulation and safety profile of adoptive immunotherapy using expanded autologous activated lymphocytes against advanced cancer.

Expanded activated autologous lymphocyte (EAAL) therapy with CD3(+)CD8(+) cytotoxic T lymphocyte and CD3(-)56(+) natural killer cell as the major effector cells is a type of adoptive cell therapy. In this study, 19 patients with metastatic tumors received EAAL therapy. Two to four weeks after the administration of EAAL cells, the subsets of CD3(+)CD8(+) T lymphocytes and CD3(-)CD56(+) natural killer cells in the peripheral blood were increased significantly in comparison with those before the therapy. The number of IFN-γ secreting cells also significantly increased after the EAAL infusion (p=0.002) and the p values for the counts of CD3(+)IFN-γ(+) lymphocytes and CD3(-)IFN-γ(+) lymphocytes were 0.006 and 0.015, respectively. Moreover, the percentage of IFN-γ producing cells of the CD3(+), CD8(+) and CD3(-) subsets after infusion were all increased significantly, which indicated that EAAL therapy was able to enrich the potentially anti-tumor cytotoxic peripheral blood lymphocytes.

Study of the Characteristics and Comprehensive Fuzzy Assessment of Indoor Air Chemical Contamination in Public Buildings.

Quality-of-life is improving daily with continuous improvements in urban modernization, which necessitates more stringent requirements for indoor air quality. Fuzzy assessment enables us to obtain the grade of the evaluation object by compound calculation with the help of membership function and weight coefficient, overcoming the limitations of traditional methods applied to develop environmental quality indices. First, this study continuously measured SO2, O3, NO2, NO, CO, CO2, PM10, PM2.5, and other chemical pollutants during the daytime operating hours of a library and a canteen. We analyzed the concentration distributions of the particles in the air were discussed based on 31 different particle diameters. Finally, the experimental data in department store and waiting hall were analyzed by fuzzy evaluation, with the following results. (1) The library and canteen PM10 concentrations peaked at 07:45 in the morning and was elevated during the afternoon (48.9 and 59 µg/m3, respectively). (2) The Pearson correlation coefficient of the PM10 and PM2.5 concentrations in the library was 0.98. PM10 and SO2 in the canteen were negatively correlated, with a correlation coefficient of -0.65. PM2.5 and PM1 were always highly positively correlated. (3) The high concentration of particles in the library was associated with the small particle size range (0.25~0.45 µm). (4) By applying the fuzzy comprehensive evaluation method, the library grade evaluation was the highest level, and the waiting hall was the lowest. This study enhances our understanding of the indoor chemical contamination relationships for public buildings and highlights the urgent need for improving indoor air quality.

The specific immune response to tumor antigen CP1 and its correlation with improved survival in colon cancer patients.

BACKGROUND & AIMS: The present study was undertaken to determine the expression of a newly identified tumor antigen cancer-placenta 1 (CP1) in colorectal carcinoma (CRC) and explore the CP1-specific immune response in CRC patients and its correlation with patient survival. METHODS: CP1 expression was determined by reverse-transcription polymerase chain reaction, immunohistochemistry, and Western blot analysis. Serum antibodies against CP1 were detected by enzyme-linked immunosorbent assay, and T-cell response was measured by interferon-gamma/granzyme-B release enzyme-linked immunospot assays. The HLA-A2-restricted epitopes in CP1 were predicted by bioinformatics and then experimentally validated by enzyme-linked immunospot assay. RESULTS: CP1 expression was detected in a significant number of CRC tissues, reaching 47.6% at the messenger RNA (mRNA) level and 28.6% at the protein level. Of patients with CP1 mRNA(+) tumors, more than 50% had CP1-responsive CD4(+) and CD8(+) T cells and 30% spontaneous-occurring antibodies against CP1. Further studies revealed 2 dominant HLA-A2-restricted epitopes in the CP1 antigen: p31-39 and p58-66. In a follow-up study up to 33 months after surgery, 9 of the 10 patients with CP1-specific CD8 T-cell response survived, whereas 6 of the 8 nonresponders died. Kaplan-Meier analysis indicated a significant correlation between T-cell response and patient survival. CONCLUSIONS: CP1 represents a new class of tumor-specific shared antigen. Its high expression in CRC tissues, prevalence of CP1-specific immune responses in CP1 mRNA(+) CRC patients, and positive correlation with survival suggest that the antigen may be a useful target for cancer immunotherapy.

The immunosuppressive tumor microenvironment in hepatocellular carcinoma.

Increasing evidence indicates the immunosuppressive nature of the local environment in tumor. The present study was focused on analyzing the immune status within hepatocellular carcinoma. In contrast to the increasing number of CD4(+) T cells, CD8(+), CD3(-)CD56(+), CD3(+)CD56(+), and gammadeltaT cells were all found to be under-represented in tumor infiltrating lymphocytes. Notably, the relative abundance of CD3(+)CD56(+) cells appeared to be correlated with patient survival. Functional analysis demonstrated that CD4(+) cells in the tumor tended to produce more IL-10 but less IFN-gamma, whereas CD8(+) cells showed impaired capacity for the production of both IFN-gamma and perforin. Consistent with previous reports, we observed a significant increase of Foxp3(+) cells in the tumor tissue. Intriguingly, although over 90% of CD4(+)CD25(high) cells were found to be Foxp3(+), the majority of Foxp3(+) cells were identified in the CD4(+)CD25(medium) and CD4(+)CD25(-) subsets. In support of its role as a negative regulator, CD4(+)CD25(high) cells suppressed the proliferation of CD4(+)CD25(-) cells isolated from the same tissues in an APC dependent manner. In conclusion, the tumor microenvironment of hepatocellular carcinoma is featured by the presence of multiple immunosuppressive factors.

[Basic and clinical researches on amyotrophic lateral sclerosis/motor neuron disease].

This study includes three aspects: (1) we have reported some novel or rare mutations of SOD1 (Cu/Zn superoxide dismutase) gene in Chinese families of ALS/MND, and found quite different features from Western patients in polymorphisms with some candidate genes such as vascular endothelial growth factor (VEGF) in sporadic ALS/MND in China. Meanwhile, we have so for established a complete clinical database with more than 1 200 cases; (2) we have established some neurophysiologic techniques of diagnosis and differential diagnosis at early-stage for ALS/MND, which include trigemino-cervical response, sternocleidomastoid and rectus electromyography, contact heat evoked potentials, and motor unit number estimate; (3) we have attempted some experimental and clinical treatments for ALS/MND, which include gene and stem cell therapies in animal models, and a pilot clinical trial of granulocyte colony stimulating factor (G-CSF) for ALS/MND patients (NCT00397423).

HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma.

Tumor-associated antigens (TAAs) have been the most actively employed targets in the clinical diagnosis and treatment of human carcinoma, such as PSA in the diagnosis of prostate cancer and NY-ESO-1 in the immunotherapy of melanoma and other cancers. However, identification of TAAs has often been hampered by the complicated and laborsome laboratory procedures. In order to accelerate the process of tumor antigen discovery, and thereby improve diagnosis and treatment of human carcinoma, we have made an effort to establish a publicly available Human Potential Tumor Associated Antigen database (HPtaa) with potential TAAs identified by in silico computing (http://www.hptaa.org). Tumor specificity was chosen as the core of tumor antigen evaluation, together with other relevant clues. Various platforms of gene expression, including microarray, expressed sequence tag and SAGE data, were processed and integrated by several penalty algorithms. A total of 3518 potential TAAs have been included in the database, which is freely available to academic users. As far as we know, this database is the first one addressing human potential TAAs, and the first one integrating various kinds of expression platforms for one purpose.

AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia.

Mitochondrial biogenesis is one of the generally accepted regulatory mechanisms in the heart under chronic hypoxia. The precise quantity and quality control of mitochondria is critical for the survival and function of cardiomyocytes. Mitochondrial autophagy, also known as mitophagy, which selectively eliminates dysfunctional and unwanted mitochondria, is the most important type of mitochondrial quality control. However, the detailed molecular mechanisms of mitophagy in cardiomyocytes have been largely undefined. The present study investigated the role of adenosine 5'­monophosphate­activated protein kinase (AMPK) in mitophagy regulation in cardiomyocytes under chronic hypoxia. H9c2 cells were cultured under hypoxic conditions (1% O2) for different time periods. Mitochondrial biogenesis was confirmed and hypoxia was found to induce the collapse of mitochondrial membrane potential (ΛΨm) and increase the number of dysfunctional mitochondria. As expected, mitochondrial autophagy was increased significantly in cardiomyocytes exposed to hypoxic conditions for 48 h. AMPK was activated under hypoxia. Notably, when the activation of AMPK was enhanced by the AMPK agonist AICAR, mitochondrial autophagy was increased accordingly. By contrast, when AMPK activation was blocked, mitochondrial autophagy was decreased and cardiomyocyte apoptosis was increased. In conclusion, in the present study, mitophagy was activated and played a crucial role in cardioprotection under chronic hypoxia. AMPK was involved in mitophagy regulation, thereby providing a potential therapeutic target for heart diseases associated with chronic hypoxia.