As a form of traditional, complementary, and alternative medicine (TCAM), traditional Tibetan medicine has developed into a mainstay of medical care in Tibet and has spread from there to China and then to the rest of the world. Thus far, research on traditional Tibetan medicine has focused on the study of the plant and animal sources of traditional medicines, study of the histology of those plants and animals, chemical analysis of traditional medicines, pharmacological study of those medicines, and evaluation of the clinical efficacy of those medicines. A number of papers on traditional Tibetan medicines have been published, providing some evidence of the efficacy of traditional Tibetan medicine. However, many traditional Tibetan medicines have unknown active ingredients, hampering the establishment of drug quality standards, the development of new medicines, commercial production of medicines, and market availability of those medicines. Traditional Tibetan medicine must take several steps to modernize and spread to the rest of the world: the pharmacodynamics of traditional Tibetan medicines need to be determined, the clinical efficacy of those medicines needs to be verified, criteria to evaluate the efficacy of those medicines need to be established in order to guide their clinical use, and efficacious medicines need to be acknowledged by the pharmaceutical market. The components of traditional Tibetan medicine should be studied, traditional Tibetan medicines should be screened for their active ingredients, and techniques should be devised to prepare and manufacture those medicines.
Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer. The treatment of GC remains challenging as the outcomes achieved with surgery alone or adjuvant or neoadjuvant chemotherapy and radiotherapy are relatively poor. New treatment strategies are emerging and are being tested in solid tumors including GC. Over the past few years, the treatment of metastatic colorectal cancer (CRC) has made great advances, but strategies to manage GC have improved little. Multiple drug resistance is common in GC chemotherapy and targeted therapy; some patients appear to receive treatment that is suboptimal or even inefficacious. Unfortunately, there are few validated predictive biomarkers to guide the tailored treatment of GC. ToGA and AVAGAST are two phase III trials that tested the efficacy and safety of targeted agents in advanced gastric cancer (AGC), and results clearly indicated that patients need to be selected and that targeted agents are the best hope for better results. This review aims to provide an overview of potential predictive biomarkers for cytotoxic and targeted agents in GC.
In our previous study, we isolated an antitumor polypeptide, CS5931, from the sea squirt Ciona savignyi; it shares high homology with Ciona intestinalis Granulin A (GRN A). However, little is known about the anticancer effect of GRN A. In the present study, GRN A was cloned and expressed in the yeast Pichia pastoris. The polypeptide was purified to almost homogeneity using a Ni-NTA column. MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] assay reveals that GRN A displays potent cytotoxicity to several human cancer cells. The polypeptide induces cell apoptosis as analyzed by morphological observation and flow cytometry assays. This study provides evidence that GRN A possesses potential to be developed as a novel anticancer agent.
Chronic hyperlipemia increases the incidence of vascular endothelial dysfunction and can even induce cardiovascular disease. Sea buckthorn contains a host of bioactives such as flavonoids and polyphenols that can prevent the development of cardiovascular disease. The current study isolated active ingredients, polyphenols, from sea buckthorn berries (SVP) and orally administered SVP at a dose of 7-28 mg/kg. This treatment significantly reduced serum lipids, it enhanced the activity of antioxidant enzymes, and it decreased the level of serum TNF-α and IL-6. SVP also alleviate vascular impairment by decreasing the expression of eNOS, ICAM-1, and LOX-1 mRNA and proteins in aortas of rats with hyperlipidemia. Based on these findings, SVP has antioxidant action and it protects endothelium.
Incidence of bile duct injuries (BDI) is low but remains a dramatic complication after laparoscopic cholecystectomy (LC). This study aimed to assess BDI incidence and management strategies. All patients treated in our institution for BDI after LC between 2000 and 2011 were retrospectively analyzed. Patients referred from others centers were excluded. Strasberg classification was used to determine the type of lesion. Thirteen patients presented iatrogenic BDI among 2,840 consecutive cholecystectomies performed (0.46%). Four cases were classified Strasberg type A, 4 type D, and 5 type E. Injury was recognized intraoperatively in 6 cases (46%). Three of these 6 required conversions to open surgery and all but one were primary sutured on a drain; the remaining patient required immediate biliodigestive anastomosis. In 7 patients, the injury was discovered postoperatively (54%). Among them, one was treated by direct closure of a cystic leak through immediate re-laparoscopy. Six underwent initially main bile duct stenting, but 4 required delayed secondary surgery (mean time 115 days), 2 to improve bile duct drainage and 2 for biliodigestive derivation. BDI incidence remains low but management depends on the time of diagnosis. BDI are complex and require tailored treatment usually in a tertiary center for a multidisciplinary approach.
Retinoic acid receptor-related orphan receptor α (RORA) is a tumor-specific differentially methylated region. RORA mRNA expression is frequently downregulated in colorectal cancer (CRC) due to promoter methylation, and this methylation is correlated with the development of CRC. Here we investigated the correlation between the methylation status of the RORA promoter region and clinical CRC stages. The methylation status of RORA isoform 1 (RORA1) and isoform 4 (RORA4) promoters was investigated in 43 paired CRC specimens and adjacent normal tissues by quantitative DNA methylation analysis using the Sequenom MassARRAY system and bisulfite sequencing. The relationship between the methylation status of the RORA1 promoter and the CRC pathological stage was analyzed. RORA1 expression was evaluated using quantitative PCR. Sixteen of 43 CRC specimens (37%) and three CRC cell lines (Caco2, HT29, and HCT116) showed increased levels of methylation in the RORA1 promoter region compared with adjacent normal tissues, whereas no methylation was observed in the RORA4 promoter. Quantitative PCR showed downregulation of RORA1 expression both in CRC samples and cell lines. Furthermore, the RORA1 promoter hypomethylation status showed a significant correlation with unfavorable CRC stages (stages III and IV) compared with favorable stages (stages I and II, p = 0.014). Hypomethylation of the RORA1 promoter may have important clinical implications in unfavorable CRC development, and therefore, the methylation status of the RORA1 promoter may constitute a useful biomarker to determine an indication for postoperative therapy such as adjuvant chemotherapy in highly advanced CRC patients.
Early detection is the key to improve the prognosis of kidney cancer. This study profiled and identified differentially expressed serum proteins in stage T1a renal cell carcinoma (RCC) using isobaric tags for relative and absolute quantification (iTRAQ)-based mass spectrometry. A total amount of 99 serum samples including 29 patients with ccRCC, 24 patients with a benign kidney mass, 28 patients with another type of urological tumor (20 cases of transitional cell carcinoma and 8 cases of prostate cancer or a male genital tumor), and 18 healthy controls were subjected to iTRAQ-based mass spectrometry. ProteinPilot software was used to identify the differentially expressed serum proteins in RCC compared to the other three populations. Hierarchical clustering analysis according to The Cancer Genome Atlas (TCGA) RCC database was then performed as the cross-platform validation. Immunohistochemistry was performed to verify the expression of selected proteins in tissue samples from these subjects. iTRAQ identified 27 differentially expressed serum proteins in the RCC patients, and 11 of these proteins were cross validated in RCC tissues from the TCGA database. The expression of C1QC, C1QB, S100A8, S100A9, ceruplasmin, and lumican was verified and associated with the tumor stage and/or grade. There were 27 differentially expressed proteins in early-stage RCC identified by iTRAQ; among them, the expression of C1QC, C1QB, S100A8, S100A9, ceruplasmin, and lumican were associated with the tumor stage and/or grade. Further studies are needed to confirm these data for their use as biomarkers for the early detection of RCC.
The p.V37I (c.109G>A) mutation in the GJB2 gene is the common frequent cause of congenital deafness; however, its pathogenicity is debated. The present study investigated the prevalence of p.V37I in Chinese infants and young children and associated clinical characteristics. The subjects of the present study were screened for mutations in GJB2 (235delC, 299delAT, 176dell6, 35delG), SLC26A4 (IVS7-2A>G, 2168A>G), GJB3 (538C>T), and in the mitochondrial 12S rRNA gene (1555A>G, 1494C>T). Subjects with p.V37I underwent an audiological evaluation. GJB2 exon sequencing revealed that 20 subjects had p.V37I compound heterozygous mutations, one of whom had a family history; the mutations included c.235delC/p.V37I (n = 12), c.299AT/p.V37I (n = 7), and c.176del16/p.V37I (n = 1). Of the 20 subjects, 12 were referred for Universal Newborn Hearing Screening (UNHS). Nine of the 20 subjects had mild hearing loss in the better ear and 5 had moderate hearing loss in the better ear while 4 had normal hearing. Among subjects with the c.235delC/p.V37I mutation, 5 had mild hearing loss and 2 had moderate hearing loss while 3 had normal hearing. Among subjects with the c.299AT/p.V37I mutation, 3 had mld hearing loss and 3 had moderate hearing loss while 1 had normal hearing. One subject with the c.176del16/p.V37I mutation had mild hearing loss. Few studies have reported on the clinical characteristics of Chinese infants with p.V37I compound heterozygous mutations identified via screening for deafness genes and GJB2 sequencing. The c.235delC/p.V37I mutation was the most prevalent mutation found in subjects. The degree of hearing loss associated with p.V37I compound heterozygous mutations was mainly mild to moderate.
The aim of this study was to investigate the antitumor effect of simvastatin in human colon cancer and the possible underlying mechanism. We found that simvastatin dose-dependently inhibited the proliferation of human colon cancer cells Lovo and HT29 using a MTT assay. Real-time PCR and Western blotting assays showed that simvastatin significantly suppressed C35 expression at both mRNA and protein levels. Since C35 is known to have a significant oncogenic role in cancer development via promoting cell proliferation and migration, results obtained in the current study imply that downregulation of C35 expression might be involved in the antitumor effect of simvastatin on colon cancer.
Thrombomodulin (TM) is a transmembrane protein expressed on vascular endothelial cells. TM has anticoagulant and anti-inflammatory properties. It has recently been reported that TM modulates complement, an immune effector system that destroys pathogens and is also involved in inflammation. TM was demonstrated to enhance the degradation of C3b into iC3b by factor I and factor H, indicating that its role is in negative regulation in the alternative pathway of the complement system. In this study, we examined the effects of recombinant human soluble TM protein composed of the extracellular domains (rTM) on the alternative pathway. The degradation of C3b into iC3b by factor I and factor H was enhanced by rTM as assessed by SDS-PAGE, confirming the previous observation. We also found that rTM enhances the cleavage of C3 into C3b as a result of activation of the alternative pathway. These results indicate that TM has both activating and inactivating functions in the alternative pathway.
In China, grass-roots emergency public health personnel have relatively limited emergency response capabilities and they are constantly required to update their professional knowledge and skills due to recurring and new public health emergencies. However, professional training, a principal solution to this problem, is inadequate because of limitations in manpower and financial resources at grass-roots public health agencies. In order to provide a cost-effective and easily expandable way for grass-roots personnel to acquire knowledge and skills, the National Health Planning Commission of China developed an emergency response information platform and provided trial access to this platform in Anhui and Heilongjiang provinces in China. E-learning was one of the modules of the platform and this paper has focused on an e-learning pilot program. Results indicated that e-learning had satisfactorily improved the knowledge and ability of grass-roots emergency public health personnel, and the program provided an opportunity to gain experience in e-course design and implementing e-learning. Issues such as the lack of personalized e-courses and the difficulty of evaluating the effectiveness of e-learning are topics for further study.
Over the past few years, China has witnessed a surge in violence against medical personnel, including widely reported incidents of violent abuse, riots, attacks, and protests in hospitals, where doctors suffer from heavy workloads and little protection. China has engaged in serious efforts, such as investing large amounts into the healthcare system and implementing several decades of healthcare reform, to make medical care more accessible to and affordable for the public. However, incidents of violence against medical personnel have increased in intensity, reflecting deteriorating relations between medical staff and their patients in China over the past few decades. Hence, the effectiveness of healthcare legislation needs to be examined and medical reform and development of the healthcare system need to be reevaluated. Only by enhancing oversight, promoting healthcare reform, and improving the healthcare system can we repair the doctor-patient relationship and decrease violence against doctors in China.