[The value of preservation of subvalvular structures in patients with mitral and aortic valve replacement surgery and its effect on left ventricular contractility].

Objective: To discuss the clinical value of preserving subvalvular structure in mitral and aortic valve replacement surgery and its effect on left ventricular contractility. Methods: A total of 97 patients who underwent mitral valve replacement surgery in the Adult Cardiac Surgery of Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital from June 2016 to December 2018 were selected as the research subjects, of whom 45 cases were preserved subvalvular structure and 52 cases were in the total resection group (intraoperative total resection of the mitral valve and subvalvular chordae tendineae). General cardiac function indexes and left ventricular function quantitative indexes were compared before and in 3 months and 6 months after the operation of the two groups; The changes of the overall longitudinal strain of the long axis of the apex and the overall circumferential strain of the short axis of the left ventricle determined by the two-dimensional speckle tracking technology were compared before and after the operation. Results: The ages of the patients in the preservation group and the total resection group were (41.8±11.3) and (43.3±10.6) years old, respectively, and the male proportions were 58.0% (26 cases) and 44.0% (23 cases), respectively, with no significant difference (all P>0.05). The aortic occlusion time and cardiopulmonary bypass time of the patients in the preservation group were (57.8±4.5) and (78.6±6.7) min, respectively, which were longer than those in the total resection group [(48.1±4.4) and (48.1±4.4) min, respectively] (all P<0.05). The left atrial pressure of the patients in the preservation group at shutdown was (8.4±1.8) mmHg (1 mmHg=0.133 kPa), which was lower than that of the total resection group (11.3±2.5) mmHg (P<0.001). There were interaction effects between groups and time in regards to the left ventricular end-diastolic diameter ( LVEDD ), left ventricular ejection fraction ( LVEF ) and Tei index, as well as the strain rate of mitral annulus and left ventricular wall of interventricular septum of the preservation group and the total resection group (all P<0.05). LVEDD and LVEF of patients in the preservation group at 3rd month after operation were (44.7±4.0) mm and (45.5±4.2) mm, and at 6th months were (56.5±4.9)% and (58.8±5.0)%, respectively, all larger than (42.7±3.6) mm and (42.7±3.6) mm, (54.5±4.6)% and (56.3±4.8)% of the total resection group. The measured value of LVESD in the preservation group at 3rd month after surgery was (32.6±3.2) mm, which was greater than that in the total resection group (31.2±3.4) mm (P<0.05). The Tei index of patients in the preservation group at 3rd and 6th months after surgery were 1.0±0.2 and 0.8±0.2, respectively, which were lower than those in the total resection group 1.2±0.3 and 0.9±0.2 (all P<0.05). Conclusion: Preserving the subvalvular structure during mitral valve replacement surgery can better improve the patient's left ventricular function and left ventricular systolic capacity.

[Role and mechanism of miRNA-181a in nonalcoholic fatty liver disease].

Objective: To investigate the role and probable mechanism of miRNA-181a in nonalcoholic fatty liver disease. Methods: HepG2 cells were treated with palmitic acid to construct a nonalcoholic fatty liver disease cell model, and the expression of miR-181a and lipidosis in the cells were measured. Transforming growth factor-ß (TGF-ß) was used to examine the effect of miR-181a expression in HepG2 cells. The miR-181a, lipidosis, reduced glutathione and reactive oxygen species (ROS) were determined by controlling and regulating the miR-183 expression levels after transfection with miR-181 mimics and inhibitors in HepG2 cells. The miR-181a target genes were predicted by bioinformatics analysis, and verified by real-time fluorescent quantitative PCR and western blotting. The independent sample t-test was used for the comparison between the two independent samples, and the comparison between multiple groups were accorded with the normal distribution, homogeneity of variance, and one-way analysis of variance. Results: Lipidosis was significantly increased after palmitic acid treatment in HepG2 cells, and the expression level of miR-181a was significantly increased than control group. After HepG2 cells were transfected with miR-181a inhibitors, the expression of miR-181a, triglycerides and reactive oxygen species were down-regulated, and reduced glutathione, predicting the mRNA and protein expression of target gene silencing information regulator 2 related enzyme 1 were up-regulated. However, the results were contrary to the above changes after transfection with miR-181a mimics. Conclusion: miR-181a participates in lipidosis and promotes lipid peroxidation in nonalcoholic fatty liver disease. miR-181a may affect the pathogenesis and progression of nonalcoholic fatty liver disease by inhibiting the expression of silencing information regulator 2 related enzyme 1.

[Retrospective analysis of curative effect of total pelvic organ resection and anal preservation in 20 patients with recurrence of cervical cancer after radical radiotherapy].

Objective: To explore the surgical method and effect of en bloc pelvic resection and anal preservation after radical radiotherapy for cervical cancer. Methods: Clinical data of 20 cervical cancer patients with central recurrence after radical radiotherapy underwent en bloc pelvic resection in the Tumor Hospital of Zhengzhou University and Hainan Provincial People's Hospital from January 2013 to December 2017 were retrospectively analyzed. The operative time, intraoperative blood loss, length of stay, postoperative anal function and postoperative complications were evaluated. Results: The median operation time of 20 patients with anal preservation after en bloc pelvic resection was 135.2 min, the median intraoperative blood loss was 680 ml, and the median hospitalization time was 16.5 days. Among them, 18 patients had good postoperative healing, and the anal function gradually returned to normal within 6 months after surgery, defecated 1~2 times per day.One patient showed incomplete adhesion between the external colon and the anus. One patient presented with pre-sacral infection. Postoperative pathology confirmed the recurrences in 20 patients, of which 11 cases were squamous cell carcinoma, 7 cases were adenocarcinoma, 2 cases were adenosquamous cell carcinoma. Conclusions: It is safe and reliable to preserve anus after en bloc pelvic resection for cervical cancer patients with radical radiotherapy. The anus function is good enough to improve the postoperative life quality of patients significantly.

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy.

Background: Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled. Results: A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P < 0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P = 0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression. Conclusion: CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.

A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations.

BACKGROUND: A phase III trial was conducted to compare the safety and efficacy of erlotinib with that of gefitinib in advanced non-small cell lung cancer harbouring epidermal growth factor receptor mutations in exon 19 or 21. METHODS: Eligible patients were randomised to receive erlotinib (150 mg per day) or gefitinib (250 mg per day) orally until disease progression or unacceptable toxicity. We aimed to determine whether erlotinib is superior to gefitinib in efficacy. The primary end point was progression-free survival. RESULTS: A total of 256 patients were randomised to receive erlotinib (N=128) or gefitinib (N=128). Median progression-free survival was not better with erlotinib than with gefitinib (13.0 vs 10.4 months, 95% confidence interval (CI) 0.62-1.05, P=0.108). The corresponding response rates and median overall survival were 56.3% vs 52.3% (P=0.530) and 22.9 vs 20.1 months (95% CI 0.63-1.13, P=0.250), respectively. There were no significant differences in grade 3/4 toxicities between the two arms (P=0.172). CONCLUSIONS: The primary end point was not met. Erlotinib was not significantly superior to gefitinib in terms of efficacy in advanced non-small cell lung cancer with epidermal growth factor receptor mutations in exon 19 or 21, and the two treatments had similar toxicities.

[Research advances of relationship between non-alcoholic fatty liver disease and biliary tract diseases].

Recent studies have found that non-alcoholic fatty liver disease(NAFLD) has great impact on the development of biliary tract diseases. Here in this review, we summarized the relationship between NAFLD and the occurrence and development, risk factors and severity of cholestasis, gallstones, intrahepatic cholangiocarcinoma, primary biliary cirrhosis and bile microbiota, so as to further illuminate the pathogenesis of NAFLD and biliary tract diseases, obtain better diagnostic and therapeutic outcomes on NAFLD and biliary tract diseases.

[Advances in research on primary resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer patients].

Lung cancer is one of the most common cancers worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers. Chemotherapy for patients with advanced NSCLC has only marginally improved overall survival; whereas recently developed small-molecule compound epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate strong efficacy in treating advanced NSCLC. However, only a part of patients with NSCLC is sensitive to the treatment of EGFR TKIs if they have certain mutations of EGFR gene in their tumors. Patients without EGFR mutations show innate resistance to EGFR TKIs. Furthermore, approximately 20%-30% of patients with EGFR mutations also do not response to EGFR TKIs. In this review, the mechanisms underlying the primary resistance to EGFR TKIs in advanced NSCLC, especially in those with EGFR sensitive mutations, are summarized.

[Diagnosis and treatment of Tuberculous primary psoas abscess].

Objective: To retrospective analysis the clinical characteristics of diagnosis and treatment the disease of tuberculous psoas abscess (TPA). Method: The medical records of 13 consecutive patients presenting to our hospital with TPA were reviewed from November 2002 to December 2015.Demographic data, presenting features, predisposing factors and the investigations performed were recorded and the outcomes were analysed. Results: The thirteen patients were included, 11 cases all had lower backache, 6 cases had Lower abdomen or groin area pain, 2 cases had fever, eleven cases were treated with Open drainage, one with Ultrasound guided drainage, and the last case used antibiotics alone, median hospital stay of 35 days, follow-up showed no recurrence or death in patients. Conclusion: The incidence of TPA is probably underreported.The vague presentation leads to delays in diagnosis and increases morbidity and a high index of suspicion is the key to early diagnosis.Open drainage has Lower recurrence and death rates, and used widely, is the most reliable method for the treatment of primary tuberculous psoas abscess.

Double-loop locking cross-stitch suture and suspension fixation for medial collateral ligament origin reconstruction.

The purpose of this study was to summarize the clinical application and results of the double-loop locking cross-stitch suture and suspension fixation method for medial collateral ligament origin reconstruction. Thirty-six patients (21 males, 15 females) with an average age of 40 years (range = 17-58 years), who underwent treatment for acute fracture of the medial collateral ligament at our hospital from February 2008 to May 2009, were included in this study. All patients presented unilateral injuries (17 right-sided, 19 left-sided) and underwent repair with the double-loop locking cross-stitch suture and suspension fixation method. All incisions in this group of patients healed by first intention. Thirty-two patients were followed up for 6-20 months (average = 12 months). There were no reports of wound infection, ligament re-fracture or other complications in the follow-up period. Based on the Lysholm knee-scoring scale, the patients received a 100% excellent and good rating (20 patients - excellent score, 12 patients - good score) postoperatively. The advantages of the double-loop locking cross-stitch suture and suspension fixation method are a smaller incision, reliable fixation, and early restoration of knee joint stability. It is, therefore, an effective and low-risk method for the reconstruction of medial collateral ligament origin.

Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression.

OBJECTIVE: To determine whether autophagy contributes to the pathogenesis of degenerative disc disease (DDD) or retards the intervertebral disc (IVD) degeneration, and investigate the possible relationship between compression-induced autophagy and intracellular reactive oxygen species (ROS) in nucleus pulposus (NP) cells in vitro. METHODS: The autophagosome and autophagy-related markers were used to explore the role of autophagy in rat NP cells under compressive stress, which were measured directly by electronic microscopy, monodansylcadaverine (MDC) staining, immunofluorescence, western blot, and indirectly by analyzing the impact of pharmacological inhibitors of autophagy such as 3-methyladenine (3-MA) and chloroquine (CQ). And the relationship between autophagy and apoptosis was investigated by Annexin-V/propidium iodide (PI)-fluorescein staining. In addition, ROS were measured to determine whether these factors are responsible for the development of compression-induced autophagy. RESULTS: Our results indicated that rat NP cells activated autophagy in response to the same strong apoptotic stimuli that triggered apoptosis by compression. Autophagy and apoptosis were interconnected and coordinated in rat NP cells exposed to compression stimuli. Compression-induced autophagy was closely related to intracellular ROS production. CONCLUSIONS: Enhanced degradation of damaged components of NP cells by autophagy may be a crucial survival response against mechanical overload, and extensive autophagy may trigger autophagic cell death. Regulating autophagy and reducing the generation of intracellular ROS may retard IVD degeneration.

Effect of surgery treatment on hypersplenism caused by cirrhotic portal hypertension.

AIM: Aim of the study was to summarize the types and quantities of peripheral hematocytopenia in the patients of hypersplenism caused by cirrhotic portal hypertension and investigate the effect of surgery, including splenectomy on the patient's peripheral blood cells and liver function. METHODS: The quantities of peripheral blood cells in the 322 patients of hypersplenism, caused by cirrhotic portal hypertension, were retrospectively studied. Then, the preoperative and postoperative values of peripheral blood cells and liver function were compared in 266 patients who were followed up. The liver function was scored and graded according to Child-Pugh scoring system. RESULTS: The study enrolled 322 patients who showed hematocytopenia, including multi-hemocyte decrease in 206 patients (64%) and simple hemocyte decrease in 116 patients (36%). After surgical treatment in the 226 patients who were followed up, the quantities of peripheral blood cells significantly increased (P<0.01), Child-Pugh grade A increased by 32 patients (14.2%), while Child-Pugh grade C increased only by 2 patients (0.9%), the liver function scores decreased (P<0.05). CONCLUSION: Hypersplenism caused by cirrhotic portal hypertension mainly manifests as a multi-hemocyte decrease and rarely shows single types of hematocytopenia. Surgical intervention including splenectomy can increase the reduction of hemocytes and promote the recovery of liver function.

Analysis of 120 pediatric patients with nonmalignant disorders transplanted using unrelated plasma-depleted or -reduced cord blood.

BACKGROUND: Unrelated cord blood (CB) is an important stem cell source for unrelated hematopoietic cell transplantation (HCT) of patients with nonmalignant disorders. Processing methods to prepare red blood cell-reduced CB units incur significant nucleated cell loss. In contrast, plasma depletion or reduction (PDR) processing of CB units entails the removal of only a portion of the plasma with minimal nucleated cell loss. However, there are relatively limited data regarding outcomes of CB transplants using units processed by PDR. STUDY DESIGN AND METHODS: A Center for International Blood and Marrow Transplant Research (CIBMTR)-audited analysis was performed on 120 pediatric patients with nonmalignant disorders transplanted between November 2001 and January 2008 at 29 US and 17 international centers using PDR CB units from two CB banks. RESULTS: Transplant characteristics were as follows: median age, 3.5 years (range, 0.1-14 years); median patient weight, 15 kg (range, 4-61 kg); 58% male; HLA matches (intermediate-resolution HLA-A and HLA-B and high-resolution HLA-DRB1) of the units used in these patients six of six in 26, five of six in 48, four of six in 47, and three of six or two of six in 6; median prefreeze total nucleated cell dose, 10.5×10(7)/kg; median prefreeze CD34+ dose, 3.7×10(5)/kg; and nonmyeloablative regimen in 24%. The median times to myeloid and platelet engraftment were 21 and 49 days, respectively. The cumulative incidence of reported Grade II to IV acute graft-versus-host disease (aGVHD) was 38±5%, and 19±4% had Grade III to IV aGVHD. The Kaplan-Meier estimates of 3-year transplant-related mortality, overall survival, and disease-free survival were 20±4, 79±4, and 70±6%, respectively. CONCLUSION: These data demonstrate the effectiveness of PDR CB units for HCT.

Composition analysis of fatty acids and stereo-distribution of triglycerides in human milk from three regions of China.

Understanding the components composition characteristics of human milk is conductive for the development of infant formulas. The total fatty acids composition and the stereo-distribution of fatty acids in human milk triglycerides (TGs) from three regions (Zhengzhou, Wuhan and Harbin) of China were analyzed. The total and intrapositional fatty acids composition of human milk TGs showed significant differences among three regions. Zhengzhou, Harbin and Wuhan human milk possessed highest levels of medium-chain fatty acids (MCFA, 6.36 ±â€¯1.46%), short-chain fatty acids (SCFA, 0.10 ±â€¯0.03%) and monounsaturated fatty acids (MUFA, 34.61 ±â€¯0.45%), and polyunsaturated fatty acids (PUFA, 30.34 ±â€¯0.33%), respectively. The preference distribution of fatty acids in human milk TGs was hardly affected by regions, for the relative conservative interpositional levels of each fatty acids in three regions. Not only the specific distribution of sn-2 position, but the esterification of fatty acids in sn-1 and sn-3 positions also had preference. SCFA and MCFA were mainly esterified at sn-3 position, but LCSFA most unlikely distributed at the sn-3 position. The preference esterification of MUFA were sn-1, sn-3 > sn-2, and PUFA were sn-3 > sn-1 > sn-2. Therefore, the optimization of infant formulas not only needs considering total fatty acid composition of TGs but requires thinking over the stereo-distribution of fatty acids.

Structure of an oxygen-carrying cobalt complex.

Bis(3-fluorosalicylaldehyde) ethylenediimine cobalt(II), a reversible oxygen-carrying compound, has been crystallized as a tetramer with two oxygen molecules bound to the four cobalt atomns, each oxygen molecule bridging between two metal atoms. These dimers are further linked by two bonds between the oxygen atom of the salicylaldehyde and the cobalt atom. The oxygen-to-oxygen distance, 1.21 angstroms in molecular oxygen, has increased to 1.308(28) angstroms (where the number in parentheses is the estimated standard deviation) in this compound, the shortest distance yet observed in sutch a bridging arrangement.

Structure of the DNA-Eco RI endonuclease recognition complex at 3 A resolution.

The crystal structure of the complex between Eco RI endonuclease and the cognate oligonucleotide TCGCGAATTCGCG provides a detailed example of the structural basis of sequence-specific DNA-protein interactions. The structure was determined, to 3 A resolution, by the ISIR (iterative single isomorphous replacement) method with a platinum isomorphous derivative. The complex has twofold symmetry. Each subunit of the endonuclease is organized into an alpha/beta domain consisting a five-stranded beta sheet, alpha helices, and an extension, called the "arm," which wraps around the DNA. The large beta sheet consists of antiparallel and parallel motifs that form the foundations for the loops and alpha helices responsible for DNA strand scission and sequence-specific recognition, respectively. The DNA cleavage site is located in a cleft that binds the DNA backbone in the vicinity of the scissile bond. Sequence specificity is mediated by 12 hydrogen bonds originating from alpha helical recognition modules. Arg200 forms two hydrogen bonds with guanine while Glu144 and Arg145 form four hydrogen bonds to adjacent adenine residues. These interactions discriminate the Eco RI hexanucleotide GAATTC from all other hexanucleotides because any base substitution would require rupture of at least one of these hydrogen bonds.

Crystal structure of Cd,Zn metallothionein.

The anomalous scattering data from five Cd in the native protein were used to determine the crystal structure of cadmium, zinc (Cd,Zn) metallothionein isoform II from rat liver. The structure of a 4-Cd cluster was solved by direct methods. A 2.3 A resolution electron density map was calculated by iterative single-wavelength anomalous scattering. The structure is folded into two domains. The amino terminal domain (beta) of residues 1 to 29 enfolds a three-metal cluster of one Cd and two Zn atoms coordinated by six terminal cysteine thiolate ligands and three bridging cysteine thiolates. The carboxyl terminal domain (alpha) of residues 30 to 61 enfolds a 4-Cd cluster coordinated by six terminal and five bridging cysteine thiolates. All seven metal sites have tetrahedral coordination geometry. The domains are roughly spherical, and the diameter is 15 to 20 A; there is limited contact between domains. The folding of alpha and beta is topologically similar but with opposite chirality. Redundant, short cysteine-containing sequences have similar roles in cluster formation in both alpha and beta.

Molecular structure of troponin C from chicken skeletal muscle at 3-angstrom resolution.

The x-ray structure of chicken skeletal muscle troponin C (TnC), the Ca2+-binding subunit of the troponin complex, shows that the protein is about 70 angstroms long with an unusual dumbbell shape. The carboxyl and amino domains are separated by a single long alpha helix of about nine turns. Only the two high-affinity Ca2+-Mg2+ sites of the COOH-domain are occupied by metal ions resulting in conformational differences between the COOH- and NH2-domains. These differences are probably important in the triggering of muscle contraction by TnC. Also the structure of TnC is relevant in understanding the function of other calcium-regulated proteins, in particular that of calmodulin because of its strong similarity in amino acid sequence.

Crystallographic structure of the octameric histone core of the nucleosome at a resolution of 3.3 A.

The structure of the (H2A-H2B-H3-H4)2 histone octamer has been determined by means of x-ray crystallographic techniques at a resolution of 3.3 angstroms. The octamer is a prolate ellipsoid 110 angstroms long and 65 to 70 angstroms in diameter, and its general shape is that of a rugby ball. The size and shape are radically different from those determined in earlier studies. The most striking feature of the histone octamer is its tripartite organization, that is, a central (H3-H4)2 tetramer flanked by two H2A-H2B dimers. The DNA helix, placed around the octamer in a path suggested by the features on the surface of the protein, appears like a spring holding the H2A-H2B dimers at either end of the (H3-H4)2 tetramer.