A novel germline frameshift mutation in the MLH1 gene in a patient with Lynch syndrome.

Lynch syndrome (LS) is an autosomal dominant inherited disorder, characterized by a predisposition to various cancers, mainly colorectal cancer (CRC). LS is caused by germline mutations in DNA mismatch repair genes i.e. mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and post-meiotic segregation increased 2 (PMS2). In this study, we report a novel germline frameshift mutation in the MLH1 gene [NM_000249: exon1: c.99dup p.(Glu34ArgfsTer4)] in a 34-year-old male patient with LS. This MLH1 alteration has never been reported in any database or any publications. The frameshift mutation in MLH1 gene [NM_000249: exon1: c.99dup p.(Glu34ArgfsTer4)] was confirmed by Sanger sequencing conducted on peripheral blood of the proband. Meanwhile, Sanger sequencing results revealed the proband's uncle was the carrier. As multiple downstream germline frameshift mutations of this variation are pathogenic, such as MLH1 M35fs, N38fs, and S44fs, it is predicted that MLH1 p.(Glu34ArgfsTer4) might be also pathogenic. Meanwhile, this MLH1 mutation p.(Glu34ArgfsTer4) is predicted to be disease-causing by the MutationTaster software, as the duplication c.99dupA introduced a premature stop codon early in the translation, resulting in a non-functional protein. This study may contribute to the mutational spectrum of MLH1 leading to LS.

Chinese cross-culturally adapted patient-reported outcome measures (PROMs) for knee disorders: a systematic review and assessment using the Evaluating the Measurement of Patient-Reported Outcomes (EMPRO) instrument.

BACKGROUND: Knee patient-reported outcome measures (PROMs) are widely used in research in China, but there is limited evidence on the quality of cross-culturally adapted and original Chinese PROMs. We investigated Chinese language knee PROMs to provide evidence for clinicians on their quality and to guide PROM choices. METHOD: A systematic literature search of databases: PUBMED, CINAHL, EMBASE, and CNKI, using adequate search strings and a three-step screen process identified relevant studies. An independent standardized assessment of the selected studies based on the Evaluating the Measurement of Patient-Reported Outcomes (EMPRO) tool was performed. Inter-rater reliability was assessed using intraclass coefficients (ICC). RESULTS: Thirty-three articles corresponding to 23 knee PROMs were evaluated with EMPRO global scores (100) ranging from 11.11 to 55.42. The attributes 'reliability,' 'validity,' and 'cultural and language adaptation' were significantly better evaluated compared to the attributes 'responsiveness,' 'interpretability,' and 'burden' (for all comparisons p < 0.0001). Moderate-to-excellent inter-rater agreement was observed with ICC values ranging from 0.538 to 0.934. CONCLUSION: We identified six PROMs with a minimum acceptable threshold (> 50/100). The osteoarthritis of knee and hip quality of life, the lower extremity function scale, and the Western Ontario Meniscal Evaluation tool ranked highest. Nevertheless, no single PROM had evidence encompassing all EMPRO attributes, necessitating further studies, especially on responsiveness, interpretability, and burden. We identified duplication of effort as shown by repeated translations of the same PROM; this inefficiency could be ameliorated by rapid approval of Chinese language PROMs documented on original PROM developers' platforms.

An anatomical feasibility study using CTA reconstruction for modified percutaneous lumbar vertebroplasty.

BACKGROUND: Lumbar vertebroplasty via several different types of extrapedicular approach has been reported with acceptable clinical results yet the anatomical basis for its safety is not fully explored. Injury to the lumbar arteries (LAs) is one of the most important potential complications. However, anatomical research on the course and variability of this structure is lacking. To investigate the anatomical feasibility of percutaneous vertebroplasty for lumbar osteoporotic vertebral compression fractures via a unilateral Extrapedicular approach. METHODS: A total of 300 LAs of 30 patients with non-spinal disorders were retrospectively analyzed by computed tomographic angiography (CTA). The lateral aspect of the vertebral body was divided into 9 zones of approximately equal area. The anatomy and orientation of LAs were analyzed in detail. RESULTS: LAs were most commonly found in the middle third of the body (zones 4, 5, and 6); the upper 1/3 of the vertebral body had LAs distributed only anteriorly and laterally (zones 1 and 2). No arteries were observed in the postero-superior segment (zone 3). From L1 to L3 an arched pattern predominated. At L4 an inferior oblique pattern (antero-superior to postero-inferior) predominated. Limited CTA visualization at L4 and particularly L5 as well as greater anatomical variation means that there is more uncertainty at these levels. CONCLUSION: From L1 to L3, the posterior superior segment (zone 1) of the vertebral body appears to be a safe area with low risk of arterial injury. This has relevance for design of a safe lumbar vertebral extrapedicular approach.

A combination of methylation and protein markers is capable of detecting gastric cancer detection by combined markers.

Aim: This study aimed to validate a combination of mSEPT9, mRNF180 and CA724 for gastric cancer (GC) detection. Patients & methods: The performance of mSEPT9, mRNF180 and CA724 was examined in a prospective cohort study with 518 participants (151 with GC, 56 with atrophic gastritis, 87 with other gastrointestinal diseases and 224 with no evidence of disease). Results:mSEPT9, mRNF180 or CA724 alone detected 48.3, 37.1 and 43.1% of GC, respectively. The combination of mSEPT9 and mRNF180 detected 60.3% of GC, and the combination of all three markers detected 68.6% of GC. The detection sensitivity of mSEPT9 and mRNF180 was significantly higher for gastric body and in elder subjects. mSEPT9 was correlated with poorer GC survival. Conclusion: The combination of mSEPT9, mRNF180 and CA724 was adequately sensitive for GC detection. The blood mSEPT9 was predictive for GC prognosis.

Lay abstract Gastric cancer is the most common cancer type in the digestive system. In this study we developed an effective and convenient blood-based test to detect gastric cancer. This test combined a conventional protein test with a newly invented methylation test. We aimed to validate the test and examine its performance using a prospective cohort study. The study showed that the test has promising potential for noninvasive early detection of gastric cancer. We found that single protein or methylation markers detected a proportion of gastric cancer cases, while a combination of these markers exhibited maximal detection capability. Therefore we concluded that the combined test provided adequate efficacy and should be used as a strategy for future gastric cancer detection.

The enhancement of Tetrandrine to gemcitabine-resistant PANC-1 cytochemical sensitivity involves the promotion of PI3K/Akt/mTOR-mediated apoptosis and AMPK-regulated autophagy.

BACKGROUND: In the process of tumor development, the resistance of pancreatic cancer cells to gemcitabine (GEM) is mainly due to the suppression and dysregulation of apoptosis signals to a large extent. Therefore, it is very necessary to develop pro-apoptotic drugs for combined treatment of pancreatic cancer to increase the activity of GEM and improve the prognosis of pancreatic cancer. METHODS AND RESULTS: GEM-resistant PANC-1 cells were treated with increasing doses of GEM. The effects of GEM and TET on apoptosis were evaluated by flow cytometry and Hoechst 33258 staining. We also evaluated the expression of survivin by real-time PCR, and the expression levels of proteins involved in apoptosis, autophagy, and PI3K/Akt/mTOR signaling were detected by western blotting. The results showed that TET downregulated expression of survivin by inhibiting the PI3K/Akt/mTOR signaling pathway to promote pancreatic cancer cell apoptosis, thereby enhancing pancreatic cancer cell sensitivity to GEM. Moreover, TET enhanced cytotoxic and autophagy-dependent cell death by upregulating the AMPK-autophagy axis, and this effect was reversed by inhibition of AMPK. CONCLUSIONS: TET promotes apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway and promotes autophagy via up-regulating the AMPK signaling pathway to play an anti-tumor effect in GEM-resistant pancreatic cancer cells, which represents a new therapeutic strategy for the treatment of GEM-resistant pancreatic cancer.

Minimally invasive debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis: a long-term follow-up study.

BACKGROUND: Spondylodiscitis is an unusual infectious disease, which usually originates as a pathogenic infection of intervertebral discs and then spreads to neighboring vertebral bodies. The objective of this study is to evaluate percutaneous debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis. METHODS: From January 2002 to May 2017, 23 patients with multilevel spondylodiscitis were treated with minimally invasive debridement and drainage procedures in our department. The clinical manifestations, evolution, and minimally invasive debridement and drainage treatment of this refractory vertebral infection were investigated. RESULTS: Of the enrolled patients, the operation time ranged from 30 minutes to 124 minutes every level with an average of 48 minutes. Intraoperative hemorrhage was minimal. The postoperative follow-up period ranged from 12 months to 6.5 years with an average of 3.7 years. There was no reactivation of infection in the treated vertebral segment during follow-up, but two patients with fungal spinal infection continued to progress by affecting adjacent segments prior to final resolution. According to the classification system of Macnab, one patient had a good outcome at the final follow-up, and the rest were excellent. CONCLUSIONS: Minimally invasive percutaneous debridement and irrigation using intraoperative CT-Guide is an effective minimally invasive method for the treatment of multilevel spondylodiscitis.

Molecular Targets for Improving Arteriovenous Fistula Maturation and Patency.

The increasing prevalence of chronic and end-stage renal disease creates an increased need for reliable vascular access, and although arteriovenous fistulae (AVF) are the preferred mode of hemodialysis access, 60% fail to mature and only 50% remain patent at one year. Fistulae mature by diameter expansion and wall thickening; this outward remodeling of the venous wall in the fistula environment relies on a delicate balance of extracellular matrix (ECM) remodeling, inflammation, growth factor secretion, and cell adhesion molecule upregulation in the venous wall. AVF failure occurs via two distinct mechanisms with early failure secondary to lack of outward remodeling, that is insufficient diameter expansion or wall thickening, whereas late failure occurs with excessive wall thickening due to neointimal hyperplasia (NIH) and insufficient diameter expansion in a previously functional fistula. In recent years, the molecular basis of AVF maturation and failure are becoming understood in order to develop potential therapeutic targets to aide maturation and prevent access loss. Erythropoietin-producing hepatocellular carcinoma (Eph) receptors, along with their ligands, ephrins, determine vascular identity and are critical for vascular remodeling in the embryo. Manipulation of Eph receptor signaling in adults, as well as downstream pathways, is a potential treatment strategy to improve the rates of AVF maturation and patency. This review examines our current understanding of molecular changes occurring following fistula creation, factors predictive of fistula success, and potential areas of intervention to decrease AVF failure.

BATF2 inhibits chemotherapy resistance by suppressing AP-1 in vincristine-resistant gastric cancer cells.

PURPOSE: Chemotherapy remains the primary treatment used to improve overall survival and quality of life for patients with gastric cancer (GC); however, multidrug resistance is a major reason underlying failure of chemotherapy. Drug resistance (DR) can arise because of molecular changes inhibiting drug-target interactions; for example, overexpression of drug efflux pumps, such as P-gp, mediated by the activation of AP-1. BATF2 is a suppressor of AP-1; therefore, this study aimed to determine how BATF2 interacts with AP-1to inhibit DR in GC cells. METHODS: Expression of BATF2 in drug-responsive and non-responsive GC tumor tissues was evaluated by quantitative PCR and western blotting. Further, expression levels of BATF2- and AP-1-related genes were confirmed in vincristine-resistant SGC7901/VCR cells treated with cisplatin or 5-fluorouracil. A BATF2 overexpression system was established in SGC7901/VCR cells, and then AP-1 also overexpressed in the cells with upregulated BATF2 levels. Further, an AP-1 knockdown system was generated in SGC7901/VCR cells. MTT and flow cytometry assays were performed in the BATF2/AP-1 overexpression system, to evaluate cell proliferation, cell cycle effects, and apoptosis, and the expression of various proteins was detected by western blotting in AP-1/BATF2 overexpression cells. Finally, the effects of BATF2 overexpression in an in vivo nude mouse GC model were evaluated. RESULTS: We found that BATF2 was overexpressed in tissues from patients with non-responsive GC and the VCR resistance cell line, SGC7901/VCR, while levels of c-Fos and c-Jun were reduced in the SGC7901/VCR cell line. BATF2 overexpression suppressed levels of AP-1 and P-gp. Further, our data demonstrate that cell proliferation is suppressed, and the cell cycle and apoptosis are induced in SGC7901/VCR cells overexpressing both AP-1 and BATF2. Overexpression of AP-1 restored levels of genes downstream of AP-1 in BATF2 overexpressing cells. Compared with controls, tumor growth of SGC7901/VCR cells in nude mice was suppressed in the BATF2 overexpression group. CONCLUSION: AP-1 down-regulation by BATF2 overexpression or AP-1 knockdown can inhibit DR in GC cells. These findings suggest that BATF2 inhibits DR in SGC7901/VCR GC cells by down-regulating AP-1 expression.

Carotid Endarterectomy and Carotid Artery Stenting for Patients With Crescendo Transient Ischemic Attacks: A Systematic Review.

Importance: Thromboembolic stroke attributable to an ipsilateral carotid artery plaque is a leading cause of disability in the United States and a major source of morbidity. Randomized clinical trials have demonstrated the efficacy of carotid endarterectomy and carotid stenting at minimizing stroke risk in patients with minor stroke and transient ischemic attack. However, there is no consensus on guidelines for medical management and the timing of revascularization in patients with multiple recurrent episodes of transient ischemic attack over hours or days, an acute neurological event known as crescendo transient ischemic attack. Objective: To review the management of and timing of intervention in patients presenting with crescendo transient ischemic attack. Evidence Review: This systematic review included all English-language articles published from January 1, 1985, to January 1, 2019, available from PubMed (MEDLINE) and Google Scholar. Articles were excluded if they did not include analysis of patients with symptoms, did not report the timing of intervention after crescendo transient ischemic attack, or mixed analysis of patients with stroke in evolution with patients with crescendo transient ischemic attack. The quality of the evidence was assessed with the modified rating from the Oxford Centre for Evidence-based Medicine. Observations: Patients with crescendo transient ischemic attack were found to have a higher risk of stroke or death after carotid endarterectomy compared with patients with a single transient ischemic attack or stable stroke. With medical therapy alone, a considerable number of patients with crescendo transient ischemic attack experience a completed stroke within several months and have a poor prognosis without intervention. Urgent carotid endarterectomy, typically performed within 48 hours of initial presentation, is beneficial in carefully selected patients. There have been several reports of operative treatment within the first 24 hours of presentation; however, review of these reports does not show any additional benefit from emergency treatment. Carotid artery stenting is reserved only for selected patients with prohibitive surgical risk for endarterectomy. The literature does not clearly support any additional benefit of intravenous heparin therapy over mono or dual antiplatelet therapy prior to carotid endarterectomy. Conclusions and Relevance: Crescendo transient ischemic attack is best managed with optimal medical management as well as urgent carotid endarterectomy within 2 days of presentation. Surgical endarterectomy appears to be preferred because of the increased embolic potential of bifurcation plaque, whereas stenting is an option for patients with contraindications for surgery. With ongoing advances in cerebrovascular imaging and medical treatment of stroke, there is a need for better evidence to determine the optimal timing and preoperative medical management of patients with crescendo transient ischemic attack.

The potential and limitations of induced pluripotent stem cells to achieve wound healing.

Wound healing is the physiologic response to a disruption in normal skin architecture and requires both spatial and temporal coordination of multiple cell types and cytokines. This complex process is prone to dysregulation secondary to local and systemic factors such as ischemia and diabetes that frequently lead to chronic wounds. Chronic wounds such as diabetic foot ulcers are epidemic with great cost to the healthcare system as they heal poorly and recur frequently, creating an urgent need for new and advanced therapies. Stem cell therapy is emerging as a potential treatment for chronic wounds, and adult-derived stem cells are currently employed in several commercially available products; however, stem cell therapy is limited by the need for invasive harvesting techniques, immunogenicity, and limited cell survival in vivo. Induced pluripotent stem cells (iPSC) are an exciting cell type with enhanced therapeutic and translational potential. iPSC are derived from adult cells by in vitro induction of pluripotency, obviating the ethical dilemmas surrounding the use of embryonic stem cells; they are harvested non-invasively and can be transplanted autologously, reducing immune rejection; and iPSC are the only cell type capable of being differentiated into all of the cell types in healthy skin. This review focuses on the use of iPSC in animal models of wound healing including limb ischemia, as well as their limitations and methods aimed at improving iPSC safety profile in an effort to hasten translation to human studies.

ProNGF siRNA inhibits cell proliferation and invasion of pancreatic cancer cells and promotes anoikis.

BACKGROUND: Precursor of nerve growth factor (proNGF) was previously considered biologically inactive; however, it has recently been identified as having important roles in the pathology of cancer development. AIM: This study aimed to explore the therapeutic effects of proNGF siRNA on the proliferation, invasion, and anoikis of pancreatic cancer cells and determine the functions of proNGF. METHODS: Pancreatic ductal adenocarcinoma (PDAC) and paired paracancerous tissue samples were collected from 60 patients for evaluation of proNGF expression by immunohistochemistry staining, qPCR, and western blotting. PDAC cell proliferation, migration, apoptosis, and anoikis following proNGF siRNA knockdown were investigated in two pancreatic cancer cell lines, Panc-1 and Bxpc-3, using BrdU incorporation assays, EdU staining, Ki-67 immunofluorescence (IF) staining, wound-healing assays, transwell invasion assays, and EthD-1 IF staining. Autophagy-related proteins were also measured by western blotting. RESULTS: Levels of proNGF protein were higher in pancreatic cancer tissues and cells lines than those in paracancerous tissues and normal pancreatic duct epithelial cells, respectively. In vitro, ProNGF knockdown by siRNA led to significantly reduced cell proliferation, remarkably inhibited wound-healing, and reduced the number of invaded PDAC cells in migration and transwell assays. Treatment with proNGF siRNA also downregulated ATG5 and Beclin 1 protein levels, increased those of P62, and increased EthD-1 staining in PDAC cells. CONCLUSION: ProNGF expression is elevated in PDAC tissues and cell lines, and proNGF siRNA can inhibit cell proliferation, migration, and invasion, and promote anoikis of pancreatic cancer cells, in which decreased proNGF may participate.

Unilateral macular choroidal neovascularization-a rare manifestation in acute myelocytic leukemia: Case report.

RATIONALE: Characteristic signs of leukemic retinopathy include bilateral intra-retinal hemorrhage, white-centred hemorrhage, macular hemorrhage and cotton-wool spots. Capillary closure, retinal microaneurysms and neovascularization following massive fundus hemorrhage could be involved in few of the above instances. However, single choroidal neovascularization (CNV) in macular has not been observed in acute myelocytic leukemia (AML). PATIENT CONCERNS: A 22-year-old woman presented with a 7-day history of vision decline in the right eye (OD). The patient was diagnosed as M3 AML one month earlier. Chemotherapy was immediately administered, which led to temporary myelosuppression. Recent examination showed that best corrected visual acuity was 20/400 OD. Fundoscopy showed petechial and patchy intra-retinal hemorrhage in both eyes and grayish-white lesion in the right macular center, which was confirmed as macular CNV by OCT and OCTA. DIAGNOSES: The patient was diagnosed as macular CNV OD related to AML and chemotherapeutic regimens. INTERVENTIONS: She received intravitreal ranibizumab injection 0.5 mg (10 mg/ml) in the right eye for once on January 3, 2017. OUTCOMES: CNV resolved three days after treatment with intravitreal ranibizumab injection 0.5 mg for once. No recurrence was observed after 10-month follow-up. Vision recovered to 20/40 at the last visit. LESSONS: This is the first report demonstrating that macular CNV could be an ophthalmic side-effect secondary to initiated chemotherapeutic regimens in patients with M3 AML. Intravitreal injection of ranibizumab could be beneficial and safe in treating this CNV.

Acetagastrodin effects on retinal oscillatory potentials in patients during the early stages of diabetes.

AIMS: To investigate the protective effect of acetagastrodin on visual electrophysiology in patients with early-stage diabetes. METHODS: A prospective, randomized, controlled, double-blind trial was conducted. Subjects who were randomly assigned to either the treatment group or the control group were orally administered acetagastrodin or placebo, respectively, for 6 months. The quantity, mean amplitude and mean latency of oscillatory potentials (OPs) wavelets at baseline and 6 months were measured on electroretinogram (ERG), in all subjects. RESULTS: A total of 92 right eyes in 92 patients with type 2 diabetes, who were diagnosed for the first time, were enrolled. Each group consisted of 46 cases (46 eyes). There was no significant difference in baseline characteristic between treatment and control groups at baseline, but quantity in treatment group was more than that in control group at 6 months (P = 0.001). The mean amplitude of OPs was reduced in the control group 6 months later compared with treatment group (P = 0.001). As to mean latency of OPs, statistical difference was also detectable between the treatment group and control group 6 months later (P < 0.001). No statistical differences were found in hemoglobin between both groups at 6 months (P > 0.05). CONCLUSIONS: Electrophysiological changes would go on worsening even hemoglobin was under control during the initial stage of diabetes. Acetagastrodin treatment may be an effective treatment to protect retinal neurons against such functional impairment during the early stages of diabetes.

A Randomized Controlled Trial of Conbercept Pretreatment before Vitrectomy in Proliferative Diabetic Retinopathy.

Purpose. To determine the efficacy and safety of preoperative intravitreal conbercept (IVC) injection before vitrectomy for proliferative diabetic retinopathy (PDR). Methods. 107 eyes of 88 patients that underwent pars plana vitrectomy (PPV) for active PDR were enrolled. All patients were assigned randomly to either preoperative IVC group or control group. Follow-up examinations were performed for three months after surgery. The primary bioactivity measures were severity of intraoperative bleeding, incidence of early and late recurrent VH, vitreous clear-up time, and best-corrected visual acuity (BCVA) levels. The secondary safety measures included intraocular pressure, endophthalmitis, rubeosis, tractional retinal detachment, and systemic adverse events. Results. The incidence and severity of intraoperative bleeding were significantly lower in IVC group than in the control group. The average vitreous clear-up time of early recurrent VH was significantly shorter in IVC group compared with that in control group. There was no significant difference in vitreous clear-up time of late recurrent VH between the two groups. Patients that received pretreatment of conbercept had much better BCVA at 3 days, 1 week, and 1 month after surgery than control group. Moreover, both patients with improved BCVA were greater in IVC group than in control group at each follow-up. Conclusions. Conbercept pretreatment could be an effective adjunct to vitrectomy in accelerating postoperative vitreous clear-up and acquiring stable visual acuity restoration for PDR.

[Global gene expression responses to Iodine-125 radiation in three human gastric cancer cell lines].

OBJECTIVE: To study genome-wide gene expression changes in gastric cancer cells after iodine-125 ¹²5(I) particle irradiation. METHODS: ¹²5I particles were used to irradiate three gastric cancer cell lines of various differentiation levels:high (BGC-823) , medium (AGS) and low (NCI-N87) .Whole-genome gene expression was investigated with microarray. The gene expression in iodine-125 irradiated and untreated cancer cells was compared, and the genes with transcript levels altered for at least 2 folds (P < 0.05) were selected. The change in gene expression levels was verified by using quantitative real-time (qRT) -PCR. RESULTS: The three gastric cancer cell lines received the same dose rate of ¹²5I particle irradiation. Cluster analysis showed that the Gene Ontology (GO) categories did not change in the three cell lines, but changes in gene expression levels were evident for many genes. After ¹²5I particle irradiate NCI-N87 cells, 895 genes were up-regulated, 786 genes were down-regulated; AGS was irradiated by ¹²5I seed, there were 124 genes upregulated, 161 genes were down-regulated; BGC-823 cells were treated by ¹²5I seed irradiation, 2 412 genes upregulated, 3 243 downregulated genes. After ionizing radiation can cause very complex transcriptional regulation changes, KEGG pathway analysis shows that these differentially expressed genes overlap in a particular cell pathway. Four genes, TRAF3IP2-AS1, SDC1, RABL2B and NOM, were found having at least 2-fold difference in expression (P < 0.05) , and the gene expression alteration was confirmed by qRT-PCR. CONCLUSIONS: ¹²5I particle irradiation caused gene expression changes in gastric cancer cells. The expressions of TRAF3IP2-AS1, SDC1, RABL2B and NOM are altered significantly in all three cell lines studied, indicating that these genes may play an important role in the ¹²5I seed treatment of gastric cancer. These genes could be potential targets for developing anti-cancer drugs in the future.

[Screening of mitochondrial deoxyribonucleic acid 3271T > C, 8356T > C, 9176T > C/G and 13513G > A mutations in mitochondrial encephalomyopathies].

OBJECTIVE: To investigate the spectrum of mitochondrial DNA (deoxyribonucleic acid) 3271T > C, 8356T > C, 9176T > C/G and 13513G > A mutations in Chinese patients with mitochondrial encephalomyopathies. METHODS: Peripheral blood samples were collected from 500 mitochondrial encephalomyopathies patients clinically diagnosed as mitochondrial encephalomyopathy lactic acidosis & stroke-like episodes (MELAS), myoclonus epilepsy & ragged-red fibers (MERRF) or Leigh's syndrome from October 2005 to October 2009. The methods of PCR- polymerase chain reaction-restriction fragment length polymorphism (RFLP) and PCR-sequencing were performed to identify the mutations. RESULTS: No patients with the 3271T > C, 8356T > C, 9176T > C/G or 13513G > A mutations were identified. CONCLUSION: The mutations of 3271T > C, 8356T > C, 9176T > C/G and 13513G > A are rare causes of mitochondrial encephalomyopathies in Chinese patients.

[Clinical observation of XELOX (Capecitabine puls Oxaliplatin): an adjuvant chemotherapy regimen used in stage III colorectal cancer].

OBJECTIVE: To evaluate the efficacy and safety of an adjuvant chemotherapy regimen: XELOX (Capecitabine puls Oxaliplatin) used after curative resection for stage III colorectal cancer. METHODS: From Jan. 1998 to Jan. 2004, 256 cases with stage III colorectal cancer randomized received de Gramont, modified FOLFOX4 (mFOLFOX4) and XELOX regimens. The 3-year disease-free survival (DFS) and overall survival (OS) were compared within the three groups and relative prognosis factors within mFOLFOX4 and XELOX groups. Therapeutic adverse events were recorded and analyzed with Kaplan-Meier test. RESULTS: 98, 87 and 71 cases were respectively enrolled in the de Gramont, mFOLFOX4 and XELOX groups, mFOLFOX4 and XELOX had superior efficacy compared with de Gramont regimen. The two former could significantly improve 3-year DFS (79.7% vs. 66.2%, P = 0.015; 81.5% vs. 66.2%, P = 0.004) and medium survival time (40.2 mon vs. 37.8 mon, P = 0.024; 41.4 mon vs. 37.8 mon, P = 0.014). Meanwhile they could respectively decrease the ratio of recurrence risk by 18.0% (P = 0.024) and 21.0% (P = 0.003). The relative benefit of mFOLFOX4 versus XELOX didn't differ for 3-year DFS [hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.79-1.12, P = 0.13] and OS (HR: 0.87, 95% CI: 0.84-1.06, P = 0.54). In the analysis of DFS in relative prognosis factors, XELOX had a better trend of survival advantage. mFOLFOX4 had higher adverse events within these regimens, especially in grade 3 or 4 neutropenia and peripheral neurologic adverse events. CONCLUSION: XELOX maintains its efficacy and safety ratio in advanced colorectal cancer. Patients have good tolerance and compliance. The regiment is deserves to be applied in clinical treatment. Oxaliplatin;