[Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer].

Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant (P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups (P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage (HR=2.806, 95%CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH (HR=1.841, 95%CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS (HR=2.538, 95%CI:1.169-5.512, P=0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

[Expression of FATS in non-small cell lung cancer and its relationship with prognosis].

Objective: To investigate the expression of fragile-site associated tumor suppressor (FATS) in non-small cell lung cancer and its relationship with clinicopathological features and prognosis. Methods: A total of 140 non-small cell lung cancer (NSCLC) cases and 30 adjacent normal tissues were used to detect the expression level of FATS protein, and to analyze the relationship of FATS protein expression and clinicopathological features and prognosis of NSCLC. Results: Western blot showed that the expression of FATS in adjacent normal tissues was significantly higher than that in non-small cell lung cancer tissues. The results of immunohistochemistry showed that the high expression rate of FATS in 140 cases of NSCLC was 40.0%, and the high expression rate of FATS in 30 cases of adjacent tissues was 73.3%. The difference was statistically significant (P=0.01). Further analysis showed that the TNM stage (P=0.044) and lymph node metastasis (P=0.022) were significant difference between FATS high expression group and low expression group. The 6-year overall survival (OS) rates of NSCLC patients with FATS high-expression and low-expression were 57.1% and 23.8%, respectively, and the 6-year disease-free survival (DFS) rates were 53.6% and 21.4%, respectively, with statistically significant differences (P=0.001). In Cox multivariate analysis, we found gender (HR=1.658, P=0.028; HR=1.684, P=0.023), TNM staging (HR=2.327, P=0.019; HR=2.332, P=0.013) and FATS expression (HR=0.532, P=0.010; HR=0.538, P=0.009) were independent prognostic factors for both OS and DFS of NSCLC patients. Conclusions: The expression of FATS protein is associated with the development and is an independent prognostic factor of NSCLC patients. The detection of FATS protein is expected to be a new biomarker for evaluating the prognosis of NSCLC patients.

[The diagnosis and treatment of traumatic optic nerve neuropathy combined with carotid artery injury].

Objective: To discuss the diagnosis and treatment strategy of traumatic optic nerve neuropathy (TON) combined with carotid artery injury. Methods: Retrospective analyses were performed 397 cases of TON at Neurosurgery department of Beijing Tongren Hospital, Capital Medical University (CMU), from January 2016 to December 2017.The clinical experience was concluded. Results: 9 cases of Traumatic Pseudo Aneurysm (TPA) and 16 cases of Traumatic Carotid Artery-Cavernous Sinus Fistula (TCCF) were found.7 cases of TPA were treated by covered stent, the other 2 cases were treated by detachable balloons.11 cases of TCCF were treated by detachable balloons, and 5 cases of fistulas were found spontaneously closed by DSA after 1-3 months.There was no disability rate and mortality in this study. Conclusion: TON combined with carotid artery injury was a critical situation, and sometime without obvious symptoms and sign, which was easily miss diagnosed.It should be with more concern in diagnosing and treating in such cases, to avoid disability rate and mortality.

[Antibody-based agents as experimental therapeutic interventions for corneal allograft rejection].

The corneal allograft rejection is the primary reason for graft failure, but the existing agents are of limited efficacy and may be accompanied by unacceptable morbidity. Recently, antibody-based agents have received great attention and have become an important part of therapeutic intervention for organ transplantation, which is also a research focus in the field of corneal transplantation. This review summarizes the history, current situation and mechanism of antibody-based agents in corneal transplantation.

Which of the fibrous layer is more important in the genesis of traumatic temporomanibular joint ankylosis: The mandibular condyle or the glenoid fossa?

INTRODUCTION: The aim of this experimental study was to investigate, under the premise of discectomy, whether damage to either the fibrous layer of the condyle or that of the glenoid fossa, could induce temporomanibular joint (TMJ) ankylosis. And if not, which of the fibrous layer was more important in the genesis of TMJ ankylosis. MATERIALS AND METHODS: Bilateral TMJ surgery was performed in 6 growing Xiao-wei Han sheep. Disk and condylar fibrous layer removal (DCFLR) was performed on the left TMJ, and disk and glenoid fibrous layer removal (DGFLR) was performed on the right TMJ. All animals were sacrificed at 3 months postoperatively. The TMJ complexes were examined by histological evaluation. RESULTS: Partial fibrous ankylosis was achieved on the DCFLR side in the 6 sheep at 3 months after surgery. On the DGFLR side, pathologic characteristics of TMJ osteoarthritis could be seen; however, no evidence of ankylosis was observed. The scores of TMJ ankylosis for the DGFLR side were significantly lower than those for the DCFLR side (P<0.05). CONCLUSION: This study demonstrated that removal of the condylar fibrous layer, not the glenoid fibrous layer, combined with discectomy could lead to traumatic TMJ ankylosis.

Use of induction promoters to regulate hyaluronan synthase and UDP-glucose-6-dehydrogenase of Streptococcus zooepidemicus expression in Lactococcus lactis: a case study of the regulation mechanism of hyaluronic acid polymer.

AIMS: To determine the effects of the ratios of hyaluronan synthase expression level to precursor sugar UDP-GlcA biosynthesis ability on the molecular weight (MW) of hyaluronic acid (HA) in recombinant Lactococcus lactis. METHODS AND RESULTS: The genes szHasA (hyaluronan synthase gene) and szHasB (UDP-glucose-6-dehydrogenase gene) of Streptococcus zooepidemicus were introduced into L. lactis under the control of nisA promoter and lacA promoter respectively, resulting in a dual-plasmid controlled expression system. The effects of the ratios of hyaluronan synthase expression level to the precursor sugar UDP-GlcA biosynthesis ability under different induction concentration collocations with nisin and lactose on the MW of HA in recombinant L. lactis were determined. The results showed that the final weight-average molecular weight () of HA correlated with the relative ratios of HasA (hyaluronan synthase) expression level to the concentration of UDP-GlcA. CONCLUSIONS: Regulating the relative ratios of HasA expression level to the precursor sugar biosynthesis ability was an efficient method to control the size of HA. SIGNIFICANCE AND IMPACT OF THE STUDY: This study put forward a guide to establish an efficacious way to control the size of HA in fermentation.

Current knowledge and attitudes about organ donation and transplantation among Chinese university students.

Current attitudes toward organ donation among university students in mainland China and the differences in attitudes between Chinese students in mainland China versus overseas are unknown. To address these issues, we conducted a cross-sectional survey using questionnaires among 922 Chinese undergraduates from mainland China and overseas regions of the world. Data were analyzed by descriptive statistics, Student t tests, chi-square tests, and a logistic regression analysis. We found that blood donors showed significantly better awareness of heart, liver, lung, skin, and tendon donation among commonly transplanted organs/tissues. As to the willingness for cadaveric organ donation, 61.3% of respondents consented, 8.5% objected, and 30.3% answered "not sure." The percentage holding an organ donor card was 15.7% among students from Hong Kong; 3.0%, mainland China; 2.8%, Macau; 2.6%, Taiwan, and 4.0%, other regions of the world. In a logistic regression analysis, female students (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.35 to 3.72) and blood donors (OR, 1.91; 95% CI, 1.10 to 3.32) did, but age and study specialty (medical vs nonmedical) did not show significantly more positive attitudes toward cadaveric organ donation. Compared with students from mainland China, overseas Chinese students from various regions did not show significantly different attitudes toward cadaveric organ donation. In summary, blood donors among university students have a greater knowledge of transplantation and a more positive attitude toward organ donation. Since university students are an important source of blood donors in China, they will be a potential pool of organ donors in the future.

High levels of phosphatase and tensin homolog expression predict favorable prognosis in patients with non-small cell lung cancer.

OBJECTIVE: The prognostic role of phosphatase and tensin homolog (PTEN) in non-small cell lung cancer (NSCLC) has been controversial. PATIENTS AND METHODS: In this study, levels of PTEN expression were investigated in NSCLC patients and their prognostic value in NSCLC was assessed. PTEN expression in tumor tissues from 68 NSCLC patients was analyzed using immunohistochemistry and confocal microscopy. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. RESULTS: NSCLC patients classified as expressers of high levels of PTEN (n = 46) had better prognoses than those classified as expressers of low levels (mean survival 17.1 versus 12.9 months, log-rank p = 0.038). In patients with adenocarcinoma (AC), high PTEN expression (n = 9) was associated with significantly longer survival than low PTEN expression (mean survival 23.50 versus 15.54 months, log-rank p = 0.043). High levels of PTEN expression resulted in 43% reduction in risk for all NSCLC patients (HR = 0.57, 95% CI: 0.33-0.98, p = 0.041). PTEN expression and clinical stage remained significantly associated with survival after adjustment for age, sex and tumor type (HR = 0.56, 95% CI: 0.32-0.99; p = 0.048; HR = 0.54, 95% CI: 0.36-0.97; p = 0.045). No significant difference in continuous PTEN expression levels was observed among groups with different clinical or pathological characteristics (p > 0.17). When levels of PTEN expression were binarized using the optimal cutpoint, higher levels of PTEN expression were observed in patients with T1/T2 than in those with T3/T4 (80% and 58% respectively, p = 0.049) and in patients with AC than in those with squamous-cell carcinoma (SCC) (78% and 58% respectively, p = 0.08). No significant difference in binarized PTEN expression levels was found among groups with any other clinical/pathologic characteristic (p > 0.28). CONCLUSIONS: Our results suggest that high levels of PTEN expression may be favorable prognostic marker in NSCLC patients.

Protective action of seven natural phenolic compounds against peroxidative damage to biomembranes.

The effects of seven phenolic compounds isolated from Salvia miltiorrhiza on peroxidative damage to liver microsomes, hepatocytes and erythrocytes of rats were studied. The results show that the seven compounds inhibited lipid peroxidation of rat liver microsomes induced by iron/cysteine and Vitamin C/NADPH. The hemolysis of rat erythrocytes induced by hydrogen peroxide was also inhibited. The degree of inhibition varied with different compounds. Among the seven compounds, the action of salvianolic acid A (Sai A) was the most potent. Therefore, the protective action of Sai A against peroxidative damage to isolated rat hepatocytes and their plasma membranes was evaluated further. Malondialdehyde (MDA) production and bleb of the surfaces of rat hepatocytes induced by iron/cysteine were prevented by Sai A. The production of MDA and the consumption of NADPH of the plasma membrane during lipid peroxidation initiated by iron/cysteine and Vitamin C/NADPH were also inhibited. The results strongly suggest that several phenolic compounds like Sai A have a protective action against peroxidative damage to biomembranes.

Morphologic and morphometric evaluation of the effect of ICRF-187 on bleomycin-induced pulmonary toxicity.

Morphologic and morphometric studies were made of the protective effects of ICRF-187 against the pulmonary damage induced by bleomycin in male and female C57/BL6 mice. Sixty minutes prior to the subcutaneous administration of 15 mg/kg of bleomycin, animals received either saline or ICRF-187 (300 or 150 mg/kg) intraperitoneally, twice a week for 4 weeks. The lungs of animals treated with bleomycin alone showed inflammation, hyperplasia of type II epithelial cells, squamous cell metaplasia and fibrosis. The extent of fibrosis was quantified by means of a color videometric system and histologic sections of lung stained according to a modified Masson trichrome method. The severity of these alterations, particularly of fibrosis, was reduced in all groups of animals pretreated with ICRF-187. The fibrosis was reduced to a similar extent in female mice treated with the 300 mg/kg and the 150 mg/kg doses of ICRF-187, from 39.3% to 17.6% and 13.3%, respectively. ICRF-187 induced significantly different degrees of reduction in fibrosis in the 2 groups of male mice treated with the 150 mg/kg and the 300 mg/kg doses, from 30% to 19.7% and 12.2%, respectively. In vitro studies indicated that both ICRF-187 and its open-ring hydrolysis product (ADR-925) remove iron slowly from the bleomycin-iron complex. This observation provides a basis for the concept that ICRF-187 protects by chelating iron involved in the formation of the bleomycin-Fe3+ complex that generates reactive oxygen radicals capable of causing pulmonary damage.

Metabolism of succinic acid methyl esters in myocytes.

The metabolism of the dimethyl ester of succinic acid (SAD) was examined in myocytes. When expressed in terms of CO(2) output, the oxidation of SAD (10 mM) only represented 30-40% of that of an equimolar concentration of D-glucose. Except for a modest decrease in D-[5-(3)H]glucose utilization, SAD failed to affect the catabolism of exogenous D-glucose. SAD also failed, like D-glucose, to augment O(2) consumption by the myocytes. These findings indicate that SAD is less efficiently metabolized in myocytes than in hepatocytes or pancreatic islets. It is nevertheless argued that the methyl esters of succinic acid could be efficiently used as nutrients by myocytes in situations of ATP depletion.

Long-term survival of autologous adrenal medulla grafts in the great omentum of the rat.

The omentum, a rich source for trophic and angiogenic factors, was explored as a potential intermediate transplant site to facilitate long-term survival of chromaffin tissue. Autologous rat adrenal medullas were grafted into omental pockets. All grafts became densely vascularized. The grafted chromaffin tissue exhibited strong immunoreactivities for tyrosine hydroxylase, synaptophysin and chromogranin A throughout the observation period of 16 weeks. The expression of these markers implies that grafted chromaffin cells retained the key enzyme for catecholamine biosynthesis and the organelles required for catecholamine secretion. Moreover, intermediate transplant of chromaffin tissue to the omentum could provide a favourable conditioning microenvironment thus augmenting the potential for survival of functional chromaffin tissue.

Protective effects of succinic acid dimethyl ester infusion in experimental endotoxemia.

In rats injected with bacterial lipopolysaccharide (LPS; 5 gamma mg/g body weight [BWT]), the toxin provokes death within 24 h in 23% of the animals and, in surviving rats, causes a decrease in BWT, hyperlactacidemia, hyperlipacidemia, and hyperketonemia, as well as depletion of both liver and muscle glycogen content. In the liver, LPS severely lowers the ATP and total adenine nucleotide content, ATP/ADP ratio, and adenylate charge. In hepatocytes from LPS-injected rats, the oxidation of D-glucose is first increased 2 h after administration of the toxin, despite close-to-normal phosphorylation of the hexose. In hepatocytes prepared from rats killed 24 h after injection of LPS, the phosphorylation of D-glucose, its incorporation into glycogen, and its oxidation are all severely impaired. This sequence of changes, which coincides with a decreased ratio between pyruvate and lactate production from exogenous D-glucose, is comparable to that found with agents that uncouple oxidative phosphorylation. The injection of LPS also alters the metabolic response of hepatocytes to the dimethyl ester of succinic acid (SAD), in terms, for instance, of the sparing action of the ester upon both the production of 14CO2 by hepatocytes prelabeled with L-[U-14C] glutamine and the output of NH4+, and its inhibitory action on glycogenolysis and futile cycling in the reactions catalyzed by glucokinase and glucose-6-phosphatase. Nevertheless, the infusion of SAD protects the rats against the deleterious effect of LPS upon such variables as the plasma concentration of free fatty acids and beta-hydroxybutyrate, the liver ATP content, and the oxidation of D-glucose, as well as the pyruvate/lactate ratio, in hepatocytes prepared from the LPS-injected rats. The infusion of SAD also virtually suppresses lethality in the LPS-injected animals. It is proposed, therefore, that the infusion of succinic acid esters may represent a novel therapeutic approach in endotoxemia and multiple-organ failure.

Clinicopathological and molecular genetic analysis of 4 typical Chinese HNPCC families.

AIM: To study the clinicopathological and molecular genetic characteristics of typical Chinese hereditary nonpolyposis cotorectal cancer (HNPCC) families. METHODS: Four typical Chinese HNPCC families were analyzed using microdissection, microsatellite instability analysis, immunostaining of hMSH2 and hMLH1 proteins and direct DNA sequencing of hMSH2 and hMLH1 genes. RESULTS: All five tumor tissues of 4 probands from the 4 typical Chinese HNPCC families showed microsatellite instability at more than two loci (MSI-H or RER+ phenotype). Three out of the 4 cases lost hMSH2 protein expression and the other case showed no hMLH1 protein expression. Three pathological germline mutations (2 in hMSH2 and 1 in hMLH1), which had not been reported previously, were identified. The same mutations were also found in other affected members of two HNPCC families,respectively. CONCLUSION: Typical Chinese HNPCC families showed relatively frequent germline mutation of mismatch repair genes. High-level microsatellite instability and loss of expression of mismatch repair genes correlated closely with germline mutation of mismatch repair genes. Microsatellite instability analysis and immunostaining of mismatch repair gene might serve as effective screening methods before direct DNA sequencing. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC families.

Effects of succinic acid dimethyl ester infusion on metabolic, hormonal, and enzymatic variables in starved rats.

BACKGROUND: Succinic acid dimethyl ester (SAD) is efficiently metabolized in several cell types as pancreatic islet cells, hepatocytes, and colonocytes. The purpose of this study was to assess the overall nutritional value of SAD in the whole organism. METHODS: SAD was infused at a rate of 80 micromol/g body weight per day in rats starved for either 2 or 4 days. For comparison, similar experiments were conducted in starved rats receiving an equimolar infusion of D-glucose. RESULTS: The ester failed to prevent the starvation-induced fall in body weight, paraovarian fat mass, and liver or muscle protein content. The infusion of SAD minimized, however, the decrease in plasma glucose and insulin concentrations, liver glycogen content, hepatic glucokinase activity, and islet secretory responsiveness to glucose, otherwise caused by starvation. Likewise, the infusion of SAD delayed the rise in free fatty acid and beta-hydroxybutyrate plasma concentration occurring during starvation. Nevertheless, SAD was less efficient than glucose, infused in an equimolar amount, in preventing the starvation-induced fall in liver glycogen content, decrease in the pancreatic B-cell secretory responsiveness to glucose, and stimulation of lipolysis and ketogenesis. CONCLUSIONS: SAD displays a significant nutritional value when infused in starved rats. It could thus be used as a tool to prevent the imbalance between ATP generation and use in selected metabolic situations.

Restricted effect of formycin A and non-glucidic nutrients upon insulin release in islets from rats with hereditary or acquired non-insulin-dependent diabetes.

Pancreatic islets isolated from control rats, Goto-Kakizaki rats and adult rats that were injected with streptozotocin during the neonatal period were incubated for two successive period of 90 min each in the presence of D-glucose (11.1 mM) with or without formycin A (1.0 mM), and in the presence of the dimethyl ester of succinic acid (SAD, 10.0 mM) with or without palmitate (1.0 mM). Although formycin A augmented glucose-stimulated insulin release in both control and diabetic rats, it failed to compensate for the impaired secretory response to D-glucose in the latter animals. Likewise, non-glucidic nutrients such as SAD and/or palmitate failed to display a more efficient insulinotropic action, relative to basal insulin output, in diabetic than control rats. These results indicate that both formycin A and non-glucidic nutrients are unable, through their immediate insulinotropic action, to restore a normal output of insulin in islets of animals with inherited or acquired non-insulin-dependent diabetes.

Immunological phenotypes of twelve cases of nonepidermotropic cutaneous T-cell lymphoma.

The immunologic phenotypes of 12 cases of nonepidermotropic cutaneous T-cell lymphoma are reported. All cases consisted of mature peripheral T-cells. There were 9 cases of helper T-cell (Th) phenotype and 2 cases of suppressor T cell (Ts) phenotype. One case, however, expressed both the Th and Ts phenotypes. Two separate cases displayed OKT9 positivity. OKT6 positive lymphoid cells were found in the dermis during the early and late stages of the disease. We suggest that these OKT6 positive cells should represent a dermal infiltrate of Langerhans cells of immature T-cells.

Early analysis of viremia and clinical tests in patients with epidemic hemorrhagic fever.

We analysed the early viremia and clinical tests in 82 patients with epidemic hemorrhagic fever (EHF). The results showed that the changes in viremia and clinical tests are related to the severity of the disease and prognosis. Higher concentrations of the virus in infected patients might cause a more unfavourable prognosis and more abnormalities in clinical tests. CK-MB, SGOT, SGPT, serum creatinine and urea nitrogen contents increased markedly, while serum total protein, albumin and calcium contents decreased markedly, indicating that the heart, liver and kidney in EHF patients were severely damaged. Markedly increased WBC and monocytes showed that the patients were seriously infected. Platelet count, antithrombin-III and plasminogen decreased markedly, demonstrating that there were marked changes in the coagulation-anticoagulation and fibrinolytic system of the EHF patients. Changes in RBC, Hb and HCT contents indicated that the blood in the EHF patients had a higher concentration. This study gives further evidence that EHFV plays an important role in the pathogenesis of EHF.

Interruption study of viremia of patients with hemorrhagic fever with renal syndrome in the febrile phase.

Kinetic changes of viremia were observed in 287 cases of hemorrhagic fever with renal syndrome (HFRS) in whom ribavirin was administered with double blind random control studied by means of virus isolation, indirect immunofluorescence assay and enzyme-linked immunosorbent assay. The positive rate of viremia was 79.7% (Sp = 3%) and positive rate of HERS IgM was 85% (Sp = 3.1%) before treatment. Viremia could be interrupted by ribavirin as in the ribavirin treated group, the viremia positive rate decreased, duration of viremia was shortened, viral antigen products, virus titer and HFRS IgG antibody level were reduced as compared with the control group. This showed that viremia was very frequent in patients in the febrile phase and ribavirin is an effective antiviral drug in HFRS during the febrile phase. Dosage and course of treatment of this drug are discussed.