Involvement of PD-1+CD4+ T cells in the development of traumatic tracheal stenosis by regulating the IL-17/STAT3 pathway.

Studies have highlighted an upregulation of PD-1 expression in CD4+ T cells, which accelerates lung fibrosis by activating the IL-17/STAT3 pathway, leading to IL-17A and TGF-ß1 secretion. However, the relation with traumatic tracheal stenosis (TS) remains unexplored. Our analysis found significant increases in PD-1+CD4+ T cells, IL-17A, and TGF-ß1 in the TS patients (n = 10). The cellular model used CD4+ T cells co-cultured with bronchial fibroblasts while the animal model used a nylon brush to scrape the damaged tracheal mucosa. Interventions with PD-1 and STAT3 inhibitors both in vitro (n = 5) and in vivo (n = 6) showed decreased expression of TGF-ß1 and IL-17A in CD4+ T cells, decreased collagen I synthesis in vitro, and reduced tractal fibrosis in vivo. Furthermore, PD-1's modulation of the STAT3 was evident. This research unveils PD-1+CD4+ T cells' role in TS, thus suggesting a novel immunotherapeutic strategy to counteract tracheal fibrosis.

[Development of a Ranking Tool for Scientificity, Transparency and Applicability of Clinical Practice Guidelines].

Objective: To address the limitations of existing methods and tools for evaluating clinical practice guidelines, we aimed to develop a comprehensive instrument focusing on the three main dimensions of guideline development: scientificity, transparency, applicability. We will use it to rank the guidelines according to the scores. We abbreviated it as STAR, and its reliability, validity and usability were also tested. Methods: A multidisciplinary expert working group was set up, including methodologists, statisticians, journal editors, medical professionals, and others. Scoping review, Delphi methods and hierarchical analysis were used to determine the final checklist of STAR. Results: The new instrument contained 11 domains and 39 items. Intrinsic reliability of each domain was indicated by Cronbach's α coefficient, with a average value of 0.646. The Cohen's kappa coefficients for methodological evaluators and clinical evaluators were 0.783 and 0.618. The overall content validity index was 0.905. The R2 for the criterion validity analysis was 0.76. The average score for usability of the items was 4.6, and the mean time spent to evaluate each guideline was 20 minutes. Conclusion: The instrument has good reliability, validity and evaluating efficiency, and can be used for evaluating and ranking guidelines more comprehensively.

A Cross-Sectional Study of GLIM-Defined Malnutrition Based on New Validated Calf Circumference Cut-off Values and Different Screening Tools in Hospitalised Patients over 70 Years Old.

BACKGROUND AND AIMS: The Global Leadership Initiative on Malnutrition (GLIM) is new criteria for diagnosing malnutrition that need validation adjusted to race. Our aim is to determine the optimal reference values of calf circumference (CC), investigate the prevalence of GLIM-defined malnutrition based on different screening tools in inpatients over 70 years old in China and assess its relationship with clinical outcomes. METHODS: We designed two continuity studies by analyzing a prospective multicenter database. First, we estimated and validated the CC cut-off values by receiver operating characteristic analyses against in-hospital mortality. Then the patients who were at risk by NRS 2002, MNA-SF and MUST were assessed by the GLIM criteria using the new CC values. Some clinical parameters and outcome data were evaluated. RESULTS: The optimal cut-off values of CC were 29.6 cm for male patients and 27.5 cm for female patients. The prevalence of GLIM-defined malnutrition was 27.5% by using NRS2002, 32.6% by using MNA-SF and 25.4% by using MUST. Patients with GLIM-defined malnutrition showed significantly worse values in BMI, total protein, albumin, neutrophil/lymphocyte ratio, CC, rate of complication, in-hospital mortality, length of stay, and total hospital cost than normal patients. Multivariate logistic regression showed the odds ratio of in-hospital mortality was significantly associated with GLIM defined malnutrition by using MNA-SF [OR = 1.231, 95%CI (1.022, 1.484), P = 0.029]. CONCLUSIONS: The Chinese reference values of CC for inpatients over 70 years old were validated by in-hospital mortality, which could be implemented in GLIM criteria. And this population possessed a high prevalence of nutrition risk and malnutrition. GLIM criteria with MNA-SF seems to be the first choice to diagnose malnutrition.

[Meta-analysis of the effects of supplemental parenteral nutrition on prognosis of critically ill patients].

Objective: To compare the effects of supplemental parenteral nutrition (SPN) and enteral nutrition (EN) on prognosis of critically ill patients in intensive care unit (ICU) using meta-analysis. Methods: Foreign language databases including PubMed, Embase, Cochrane Library, and Cochrane Central Register of Controlled Trials were retrieved with the search terms of " supplemental parenteral nutrition, parenteral nutrition, enteral nutrition, critically ill" , and Chinese database SinoMed database was retrieved with the search terms of ",,," to obtain the publicly published randomized controlled trials about the effects of SPN and EN supportive treatment on prognosis of critically ill patients in ICU from the establishment of each database to December 2018. The Google Scholar was retrieved for supplement. The outcome indexes included the infection rate, anti-infection time, antibiotic-free time, ICU overall mortality, overall mortality during hospitalization, mechanical ventilation time, length of ICU stay, and length of hospital stay. RevMan 5.3 and Stata 14.0 statistical software were used to conduct a meta-analysis of eligible studies. Results: A total of 794 patients were included in 8 studies, including 387 patients in SPN group who received SPN and EN and 407 patients in EN group who only received EN. The bias risks of the eight studies included were uncertain. Compared with that of EN group, the infection rate of patients in SPN group was significantly decreased (relative risk=0.79, 95% confidence interval=0.66-0.94, P<0.01). However, there were no statistically significant differences in ICU overall mortality, overall mortality during hospitalization, mechanical ventilation time, length of ICU stay, and length of hospital stay of patients between SPN group and EN group. The subgroup analysis showed that the risks of bias of studies and follow-up time might be sources of the heterogeneity of mechanical ventilation time. There was publication bias in ICU overall mortality (P<0.05), while no publication bias in the other outcome indexes (P>0.05). Conclusions: SPN supportive treatment can decrease the infection rate of critically ill patients in ICU, but it has no obvious influences on overall mortality, mechanical ventilation time, and length of hospital stay.

[Effect of an oral nutritional supplementation on nutritional status and quality of life in patients with colorectal cancer and postoperative adjuvant chemotherapy: A multi-center prospective randomized control trial].

Objective: To evaluate the effect of oral nutritional supplementation (ONS) on the nutritional status and quality of life in patients with colorectal cancer and postoperative adjuvant chemotherapy. Methods: This study was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-13003798). A multi-center randomized controlled trial was conducted. Colorectal cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy, and had nutritional risk (nutrition risk screening 2002 score ≥3) when discharge from hospital in six hospitals (Beijing Hospital, Peking University Third Hospital, Guangzhou Nanfang Hospital, Shanghai Xinhua Hospital, Shanghai Ruijin Hospital, and Shanghai The Sixth People's Hospital) from June 2013 to August 2015 were prospectively enrolled. These patients were randomly divided into the ONS group and control group. Patients in the ONS group received dietary guidance and oral nutritional supplements (2092 kJ/day, whole protein enteral nutrition) for 90 days after discharge from hospital, while patients in the control group only received dietary guidance. Anthropometric measurements (body weight, body mass index [BMI], upper arm circumference, gripping power of the dominant hand, triceps skin fold), nutrition-related laboratory tests (hemoglobin, albumin, prealbumin, total cholesterol, triglyceride), gastrointestinal function scores and quality of life (evaluated by EuroQol five dimensions questionnaire) were collected and compared at baseline (at discharge), and at 30-day, 60-day and 90-day after discharge. Results: A total of 90 patients were included into this multi-center study, of whom 5 patients dropped out, 43 patients were assigned to the ONS group and 42 patients to the control group. Compared with baseline, the body weight of patients in the ONS group increased by (1.523±0.525) kg at 60-day and (1.967±0.661) kg at 90-day, which were significantly higher than those of patients in the control group [60-day: (-0.325±0.518) kg, P=0.015; 90-day: (-0.224±0.705) kg, P=0.027, respectively]. A similar pattern was observed for BMI, the ONS group increased by (0.552±0.203) kg/m(2) at 60-day and (0.765±0.205) kg/m(2) at 90-day, which were significantly higher than those of patients in control group [60-day: (-0.067±0.202) kg/m(2), P=0.034; 90-day: (0.022±0.210) kg/m(2), P=0.013]. No significant differences of other anthropometric measurements and nutrition-related laboratory tests were found between the two groups (all P>0.05). Furthermore, there were no significant differences of improvement in gastrointestinal function and quality of life between two groups (all P>0.05). Conclusion: Oral nutritional supplements can improve the body weight and BMI of colorectal cancer patients with nutritional risk receiving postoperative adjuvant chemotherapy, though it does not improve the quality of life.

[The effect of standardized lymphectomy and sampling of resected lymph nodes on TNM staging of resectable pancreatic head cancer].

Objective: To examine the effect of standardized lymphectomy and sampling of resected lymph nodes (LN) on TNM staging of resectable pancreatic head cancer. Methods: Consecutive patients with resectable pancreatic head cancer who received standard pancreatoduodenctomy at Department of General Surgery in Beijing Hospital from December 2017 to November 2018 were recruited as study group. After operation, the surgeon sampled lymph nodes from the fresh specimen following the Japanese Gastric Cancer Guidelines.Thirty-three cases were recruited in the study group and the mean age was (59.8±15.2) years.Pathologic reports from December 2015 to November 2016 were taken as control group, containing 29 cases with age of (57.0±13.0) years. Number of lymph nodes, standard-reaching ratio and positive nodes ratio were compared between two groups. According to the seventh edition and eighth edition of TNM staging, the changes of N staging and TNM staging were analysed. The quantitative data conforming to normal distribution were tested by independent sample t test, the quantitative data not conforming to normal distribution were tested by rank sum test, and the enumeration data were analysed by χ(2) test. Results: The basal data of the two groups were comparable (all P>0.05) . The number of lymph nodes sampled in the study group was 23.27±8.87, significantly more than in control group (12.86±5.90, t=0.653, P=0.000) .Ratio of cases with more than 15 nodes was 81.8% (27/33) in the study group and 34.5% (10/29) in the control group with statistical significance (χ(2)=14.373, P=0.000) . In the study group, the positive lymph node ratios of No. 17a+17b, 14a+14b, 8a+8p LN were 36.4% (12/33) , 30.3% (10/33) and 9.1% (3/33) respectively. The positive lymph node ratio in No.14a+14b LN was higher than in No.8 LN (χ(2)=4.694, P=0.030) . According to the change in N staging system in the AJCC eighth edition, 2 cases (6.1%, 2/33) changed from ⅠB to ⅡA, 7 cases (21.2%, 7/33) from ⅡA to ⅠB and 5 cases (15.2%, 5/33) changed from ⅡB to Ⅲ (25.0%, 5/20) . Conclusions: No.14 LN should be treated as the first station rather than second station because of the anatomic character and higher metastatic ratio. Standardised lymphectomy and sampling may increase the number of LN resected and improve the TNM staging of resectable pancreatic head cancer.

[Dynamic investigation of nutritional risk in patients with malignant tumor during hospitalization].

Objective: To prospectively investigate the changes in nutritional status of patients with malignant tumors during hospitalization by using nutritional risk screening (NRS2002), and to analyze the correlation between the nutritional status and clinical outcomes . Methods: This was a prospective and parallel research done by multi-center collaboration from 34 hospitals in China from June to September 2014.Hospitalized patients with malignant tumors inthese departments (Department of Gastroenterology, respiratory medicine, oncology, general surgery, thoracic surgery and geriatrics)were investigated. Only the patients with age≥ 18 years and hospitalization time between 7-30 days were included. During hospitalization, the physical indexes of human bodywere measured, and the NRS 2002 scores, and monitored the nutritional support at the time points of admission and 24 hours before discharge were recorded.And whether there was a nutritional risk in hospitalized patients and its association with clinical outcomes were investigated. Results: A total of 2 402 patients with malignancies were enrolled in this study. Seventy fourpatients who did not complete NRS2002 were eliminated, and 2 328 patients were included. The number of the main diseases was the top five, including 587 cases of colorectal cancer, 567 cases of lung cancer, 564 cases of gastric cancer, 146 cases of esophageal cancer, and 119 cases of liver tumor. At the time of discharge, compared with admission, the BMI, body weight, grip and calf circumferences of patients with malignant tumor were significantly decreased (P<0.05). The total protein, albumin, prealbumin and hemoglobin were significantly lower than those at admission (P<0.05). In 2 328 patients who were completed nutritional risk screening, the rate of malnutrition at admission was 11.1% (BMI =18.5, 258/2 328) and the rate of malnutrition at discharge was 10.9% (BMI =18.5, 254/2 328), there were no significant differences (χ(2)=0.019 7, P=0.888). There were 1 204 patients with nutritional risk at admission (51.7%, NRS2002 score≥3)and 1 352 patients with nutritional risk at discharge (58.1%, NRS2002 score≥3), with significant differences (χ(2)=49.9, P<0.001). The incidence of nutritional risk in patients with colorectal, stomach, and lung tumors at discharge was significantly higher than that at admission (P<0.05). The infective complications and other complications of patients with nutritional risk were significantly greater than those without nutritional risk at admission and at discharge.ICU hospitalization stay of patients with nutritional risk was increased significantly than those without nutritional risk at admission(P=0.042). Hospitalization expenses of patients with nutritional risk was increased significantly than those of patients without nutritional risk at discharge(P<0.01). Conclusion: The patients with malignant tumor have a higher incidence rate of malnutrition at both admission and discharge and malnutritionhas correlation with adverse clinical outcomes.The aboveindicators did not improve significantly at discharge.Doctors should pay more attention to the nutritional status (screening and evaluation)of patients before discharge and use appropriate and adequate nutrition support in order to prevent the weight loss and improve the life quality of patients.

[Changes in nutritional status of patients with different diseases during hospitalization].

Objective: To evaluate changes in nutritional status of hospitalized patients with different diseases by subjective global assessment (SGA) and nutritional risk screening (NRS-2002). Methods: A prospective and parallel research done by multi-center collaboration from 34 hospitals in China from June to September 2014. Hospitalized patients with the following diseases were investigated: malignant tumor (2 487 cases), benign disease of the digestive system (1 358 cases), benign disease of the nervous system (1 043 cases), benign bone disease (451 cases), benign disease of the respiratory system(395 cases), cardiovascular disease (227 cases), benign thyroid and breast disease (179 cases), and endocrine disease (149 cases). Patients above the age of 18 and hospitalization time between 7-30 days were included. Physical indexes were measured, the NRS-2002 and SGA scores were recorded, the nutritional support were recorded during hospitalization and 24 hours after discharge from hospital. Measurement data between groups were analyzed using t test or Wilcoxon rank sum test, enumeration data and ranked data between groups were analyzed using chi-square test or Fisher exact test. Results: There were 6 638 cases of hospitalized patients, 3 861 cases were males and 2 777 were females, the male/female ratio was 1.4∶1.0; the median age was 60 years; the median height was 1.66 m; the median weight was 62 kg; the median body mass index (BMI)was 22.89 kg/m(2). At discharge, compared with that of admission, the body weight, BMI, grip strength, upper arm and calf circumferences of patients with malignant tumor were significantly decreased (t=20.15-259.67, all P<0.01); the body weight and calf circumference were significantly decreased (t=35.27, 60.40, P<0.01)of patients with digestive benign disease; the body weight of patients with benign bone diseases was decreased (t=2.12, P=0.033); the body weight, grip strength and upper arm circumference were decreased in patients with benign thyroid and breast disease (t=2.79-10.18, all P<0.01); nutritional risk incidence rate (from NRS-2002) of patients with malignant tumor was significantly higher(χ(2)=21.275, P=0.000); moderate malnutrition (from SGA) incidence rate was significantly higher(χ(2)=62.318, P=0.000; χ(2)=11.312, P<0.01) in patients with malignant tumor and with orthopedics diseases. Compared with that of admission, records of the patients with other diseases had no statistically difference at discharge, no more than 50% of the patients under risk of nutritional deficiency(except those with digestive benign diseases )received nutritional support, while the proportion of non-parenteral nutrition application was higher. Conclusion: The patients with malignant tumor have higher incidence rate of malnutrition on admission and at discharge. Doctors should pay more attention to the nutritional status(screening and evaluation) of patients before discharge and use appropriate and adequate nutrition support in order to prevent the weight loss and improve the life quality of patients.

[Clinical and anatomic study of preserving parathyroid specific adipose attachments in total thyroidectomy].

Objective: To discuss the anatomical characteristic and important role of specific adipose attachments in preserving parathyroid function in total thyroidectomy. Methods: Parathyroid glands of 91 cases underwent total thyroidectomy in Department of General Surgery, Beijing Hospital from January to November 2015 were observed prospectively. There were 19 male and 72 female patients, aging from 25 to 74 years with an average age of (52±12) years. Preoperative ultrasound examination, analysis of intraoperative high definition images, and postoperative pathological examination were used to detect the origins of the parathyroid micro vascular structures and the characteristics of parathyroid specific adipose attachments. Parathyroid specific adipose attachments preserving technique was used in all procedures. The results of parathyroid hormone (PTH), serum calcium and phosphorus were compared pre- and 1-month post-operatively. Paired t test was statistically used to analyze data. Results: Parathyroid micro vascular vessels were closely attached to parathyroid, and they were mainly originated from inside and (or) outside thyroid. Twenty patients received intraoperative high definition images analysis, 62 parathyroids were detected, in which 48 parathyroids (77.4%) had its specific adipose attachments. Lymphatic tissues could be distinguished from adipose tissue using carbon nanoparticles lymphatic tracer technique, which resulted in better preservation of parathyroid specific adipose attachments. There was no significant difference in PTH ((39±17) ng/L vs. (30±16) ng/L), serum calcium ((2.23±0.10) mmol/L vs. (2.20±0.14) mmol/L) and phosphorus ((1.27±0.20) mmol/L vs.(1.26±0.25) mmol/L) pre- and 1-month post-operatively (P>0.05). Conclusions: Preservation of parathyroid specific adipose attachments in total thyroidectomy could result in better protection of parathyroid micro vascular structure and function. It could be benefit to preservation of parathyroid in situ and its function recovery, thus may reduce the incidence of permanent postoperative hypoparathyroidism.

First Report of Lasiodiplodia theobromae Associated with Stem Canker of Cassia fistula in Guangxi, South China.

Cassia fistula, a member of the Fabaceae, known as the golden shower tree, is native to South Asia. It is now distributed worldwide and is popular as an ornamental plant as well as being used in herbal medicine. In October 2013, symptoms of stem canker were observed on C. fistula in a nursery (108°38' E, 22°87' N) in Nanning, Guangxi, China. The symptoms began as small brown lesions, which enlarged over several months to long, striped, slightly sunken lesions, 1 to 9 cm in width and 16 to 135 cm in length. The conspicuous cankers had vertical cracks outlining the canker and evenly spaced horizontal cracks, eventually resulting in whole plants dying back. The cankers were found on 90% of six-year-old plants in this nursery and were also observed in other plantings. On potato dextrose agar (PDA), isolates with similar morphological characteristics were consistently recovered from symptomatic plant tissues after surface sterilization in 75% ethanol for 30 sec and then in 0.1% mercuric chloride for 2 min. Over 100 conidia were examined from three isolates and were found to be elliptical and hyaline when immature, becoming dark brown, one-septate, and longitudinally striate when mature and ranging from 20 to 31 × 11 to 16 µm (average 25.5 × 13.6 µm). The rDNA internal transcribed spacer (ITS) region of isolate LC-1 was sequenced (GenBank Accession No. KM387285), and it showed 100% identity to Lasiodiplodia theobromae (Pat.) Griffon & Maubl. (GenBank KC964548), confirming the morphological identification (2) as L. theobromae (also known as Botryosphaeria rhodina (Cooke) Arx). A culture of this isolate has been preserved in the Guangxi Academy of Agricultural Sciences fungal collection. The pathogenicity of the isolate was tested on healthy twigs and branches of C. fistula trees in a field setting at Guangxi Agricultural Vocational-Technical College, Nanning, Guangxi, in June and August 2014. For each treatment, five green twigs and five 2-year-old branches were used. Five adjacent needle punctures were made on each branch with a sterilized needle. A mycelial plug was then placed on the wound of each branch and wrapped with Parafilm. Control twigs were treated with sterile PDA plugs. One week later, typical lesions were observed on the inoculated branches, with symptoms becoming more extensive after two weeks, but no symptoms were seen on the controls. Koch's postulates were fulfilled by re-isolation of L. theobromae from diseased branches. L. theobromae is recognized as an important wood pathogen and has been reported to cause cankers, dieback, and fruit and root rots in over 500 different hosts, including perennial fruit and nut trees, vegetable crops, and ornamental plants (2). The fungus has been reported on C. fistula in India since the 1970s (1); however, to our knowledge, this is the first report of L. theobromae infecting C. fistula in China. References: (1) R. S. Mathur. The Coelomycetes of India. Bishen Singh Mahendra Pal Singh, Delhi, India, 1979. (2) J. R. Úrbez-Torres et al. Plant Dis. 92:519, 2008.

Randomized clinical trial of intravenous soybean oil alone versus soybean oil plus fish oil emulsion after gastrointestinal cancer surgery.

BACKGROUND: Specific immunonutrients may reduce the incidence of postoperative complications and shorten recovery time. This randomized trial evaluated the clinical efficacy of a fish oil emulsion on outcome and immune function after gastrointestinal cancer surgery. METHODS: A total of 206 patients with gastrointestinal or colonic cancer were randomized to receive isocaloric and isonitrogenous intravenous infusions of either soybean oil alone (1.2 g per kg bodyweight per day; control group, 103 analysed) or soybean plus fish oil emulsion (1.0 and 0.2 g per kg per day respectively; treatment group, 100 analysed) over 20-24 h daily for 7 days after surgery. RESULTS: Baseline data were comparable in the two groups. There were fewer infectious complications (four versus 12 on day 8; P = 0.066), systemic inflammatory response syndrome (SIRS) was significantly less common (four versus 13; P = 0.039) and hospital stay was significantly shorter (mean(s.d.) 15(5) versus 17(8) days; P = 0.041) in the treatment group. Total postoperative medical costs were comparable in the two groups (mean(s.d.) US $ 1269(254) and 1302(324) in treatment and control groups respectively; P = 0.424). The median (interquartile range) difference in CD4/CD8 between days 1 and 8 after surgery was + 0.30 (0.06 to 0.79) in patients receiving fish oil and + 0.20 (-0.19 to 0.55) in controls (P = 0.021). No severe adverse events occurred in either group. CONCLUSION: Fish oil emulsion-supplemented parenteral nutrition significantly reduced SIRS and length of hospital stay. These clinical benefits may be related to normalization of cellular immune functions and modulation of the inflammatory response.

The effect of Malononitrilamides (FK778) on phenotypic properties of human peripheral dendritic cells.

BACKGROUND: FK778, a malononitrilamide analogue of lefunomide, is currently a promising immunosuppressive drug. Because the cellular and molecular mechanisms underlying the effects of FK778 are not entirely clarified. We studied its effects on human peripheral dendritic cells. METHODS: Peripheral blood mononuclear cells (PBMC) from 12 healthy volunteers were isolated by density separation over Ficoll solution. After resuspension in adaptive immunotherapy medium (AIM)-V medium, they were cultured without exogenous growth factors. The study group was treated with FK 778 (50 microg/mL) or Rapamycin (10 ng/mL). The phenotype of dendritic cell was ascertained by indirect immunoflurescence for analysis by flow cytometry. RESULTS: Compared with the Rapamycin-treated controls, the expressions of CD80, CD83, CD86, HLA-DA, CD54, CD62, CCR5, and CCR7 in the FK778-treated myeloid dendritic cells and the expression of CD80, CD83, CD86, HLA-DA, and CD54 in the FK778-treated plasmacytoid dendritic cells were significantly down-regulated. CONCLUSION: FK778 inhibited the differentiation and maturation of dendritic cells.

Liver transplantation in an adult patient with situs inversus: a case report and overview of the literature.

Liver transplantation (OLT) in an adult with situs inversus (SI) is extremely rare and considered a contraindication because of the anatomic difficulties. A 45-year-old male patient with complete SI, suffering from progressive hepatic failure secondary to hepatolithiasis, obstructive jaundice, and liver cirrhosis, underwent transplantation in July 2004. Preoperatively the liver anatomy was determined by computed tomography scan, three-dimensional liver reconstruction, and angiography. OLT was performed using a modified piggyback technique, the donor right lobe was rotated 45 degrees to the left, making the donor left lobe point into the left paracolic sulcus and the donor right lobe in the recipient hepatic fossa. The donor's suprahepatic vena cava was sewn end to side to the recipient vena cava, and the infrahepatic vena cava oversewn. The patient recovered uneventfully, and transplant perfusion and function were stable at a follow-up of 40 months. The present study showed OLT in adult patients with SI to be feasible. The knowledge of exact anatomy, meticulous preoperative planning, and optimization of the recipients condition are essential.

Paclitaxel-octreotide conjugates inhibit growth of human non-small cell lung cancer cells in vitro.

AIM: To evaluate the effects of paclitaxel-octreotide conjugates on the growth of cultured non-small cell lung cancer cells. METHODS: RT-PCR was performed to detect mRNA for the subtypes of the human somatostatin receptor (SSTR) using specific primers. MTT-based cytotoxicity assay was used to evaluate the cell viability after treatment with paclitaxel and the conjugates. Cell cycle perturbations were determined using a Fluorescence-Activated Cell Sorter. RESULTS: Non-small cell lung cancer A549 and Calu-6 cells expressed mRNA for SSTR2 and SSTR5. Paclitaxel and the conjugates effectively inhibited the growth of A549 and Calu-6 cells in a concentration- and time-dependent manner. In SSTR-negative fibroblasts, the conjugates were less cytotoxic than paclitaxel. The conjugates and paclitaxel could induce the increase of G(2)/M phase ratio in A549 cells. CONCLUSION: The paclitaxel-octreotide conjugates can be used as selective-targeted chemotherapeutic agents for treating non-small cell lung cancer.

Effects of sequential deletions of residues from the N- or C-terminus on the functions of epsilon subunit of the chloroplast ATP synthase.

Ten truncated mutants of chloroplast ATP synthase epsilon subunit from spinach (Spinacia oleracea), which had sequentially lost 1-5 amino acid residues from the N-terminus and 6-10 residues from the C-terminus, were generated by PCR. These mutants were overexpressed in Escherichia coli, reconstituted with soluble and membrane-bound CF(1), and the ATPase activity and proton conductance of thylakoid membrane were examined. Deletions of as few as 3 amino acid residues from the N-terminus or 6 residues from the C-terminus of epsilon subunit significantly affected their ATPase-inhibitory activity in solution. Deletion of 5 residues from the N-terminus abolished its abilities to inhibit ATPase activity and to restore proton impermeability. Considering the consequence of interaction of epsilon and gamma subunit in the enzyme functions, the special interactions between the epsilon variants and the gamma subunit were detected in the yeast two-hybrid system and in vitro binding assay. In addition, the structures of these mutants were modeled through the SWISS-MODEL Protein Modeling Server. These results suggested that in chloroplast ATP synthase, both the N-terminus and C-terminus of the epsilon subunit show importance in regulation of the ATPase activity. Furthermore, the N-terminus of the epsilon subunit is more important for its interaction with gamma and some CF(o) subunits, and crucial for the blocking of proton leakage. Compared with the epsilon subunit from E. coli [Jounouchi, M., Takeyama, M., Noumi, T., Moriyama, Y., Maeda, M., and Futai, M. (1992) Arch. Biochem. Biophys. 292, 87-94; Kuki, M., Noumi, T., Maeda, M., Amemura, A., and Futai, M. (1988) J. Biol. Chem. 263, 4335-4340], the chloroplast epsilon subunit is more sensitive to N-terminal or C-terminal truncations.

Validity of the pain anxiety symptoms scale (PASS): prediction of physical capacity variables.

Anxious responses to pain may lead to avoidance of behavior expected to produce pain. McCracken et al. (1992) developed the Pain Anxiety Symptoms Scale (PASS) to assess anxiety related specifically to pain. Efforts to validate the scale, however, have been confined mostly to examining associations between the PASS and other self-report instruments. This study tested whether PASS scores were related to behavioral performance variables recorded by therapists during a physical capacity evaluation. Participants were 98 male patients with persistent pain referred to two industrial rehabilitation centers. PASS scores were correlated negatively with amount of weight lifted and carried, and results of hierarchical regressions showed that PASS scores accounted for additional variance in these variables when measures of trait anxiety, depression and pain severity were controlled. However, we did not replicate the findings of McCracken et al. (1992) that PASS scores accounted for variance in self-reported disability with trait anxiety, depression or pain severity controlled. Results extend the validity of the PASS and are consistent with models of fear of pain: patients with high PASS scores may avoid potentially painful physical exertion to reduce their fear.

Relationships among patient hostility, anger expression, depression, and the working alliance in a work hardening program.

Hostility, anger expression, and depression may adversely affect the response of chronic pain patients to pain or functional restoration programs by hampering the development of good working alliances between patients and physical or occupational therapists. Measures of hostility, anger expression, and depression and the Working Alliance Inventory (WAI) were completed by 71 patients with chronic pain (stemming from work-related injuries) prior to starting a "work hardening" program. The physical or occupational therapist acting as any given patient's "program manager" completed the WAI, as well. Hostility and anger expression were correlated negatively only with patient ratings of the working alliance. Therapist ratings were predicted by the interaction of patient anger expression and depression, such that therapists reported their poorest alliances with patients who were both depressed and expressed anger. Results imply that hostility and the propensity to express anger may diminish a pain patient's capacity to foster a collaborative relationship with physical or occupational therapists, while therapists may readily become alienated from depressed and irritable patients.

Crystal structure of 2-debenzoyl, 2-acetoxy paclitaxel (Taxol): conformation of the paclitaxel side-chain.

Crystals of the C2-acetate analog of paclitaxel, grown from a mixture of isopropyl alcohol and methanol, belong to the space group P2(1) with a = 9.058(3), b = 18.306(5), c = 15.043(1) Angstrum, beta = 97.09(1) degrees, Z = 2, V = 2475.1(9)Angstrum3, Dcalc = 1.269 gcm-3 and mu = 0.75 cm-1. The structure was determined by direct methods and refined to R(F) = 0.054 and wR(F) = 0.057 for 605 variables and 3496 observed reflections. The paclitaxel side chain possesses a conformation similar to that observed in the crystal structure of docetaxel (Taxotere). A three dimensional network of hydrogen bonds is formed through solvent molecules and stabilizes the crystal lattice.

Malate regulation of Mg(2+)-ATPase of chloroplast coupling factor 1.

The regulatory effects of malate on chloroplast Mg(2+)-ATPase were investigated and the mechanism was discussed. Malate stimulated methanol-activated membrane-bound and isolated CF1 Mg(2+)-ATPase activity. The γ subunit of CF1 may be involved in malate regulation of the enzyme function. Modification of γ subunit at one site of the peptide by NEM may affect malate stimulation of ATPase while at another site may have no effect. The effect of malate on the Mg(2+)-ATPase was also controlled by the Mg(2+)/ATP ratio in the reaction medium. The enhancing effect of malate on Mg(2+)-ATPase activity depended on the presence of high concentrations of Mg(2+) in the reaction mixture. Kinetic study showed that malate raised the Vmax of catalysis without affecting the Km for Mg(2+) ATP. The experiments imply that the stimulation of Mg(2+)-ATPase by malate is probably correlated with the Pi binding site on the enzyme. The regulation of ATPase activity by malate in chloroplasts may be relevant to its function in vivo.