[Advances in thoracic consolidation radiotherapy after first-line immunotherapy combined with chemotherapy for extensive stage small cell lung cancer].

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

[Independent and combined effects of pre-pregnancy BMI and gestational diabetes on early adiposity rebound timing in children].

Objective: To examine the independent and combined effects of pre-pregnancy BMI and gestational diabetes (GDM) on early adiposity rebound (AR) timing in children. Methods: Based on the "Ma'anshan Birth Cohort Study", 2 896 eligible maternal and infant pairs were recruited. In the cohort, we collected pre-pregnancy height, weight, 24 to 28 weeks GDM diagnosis, follow-up at 42 days, three months, six months, nine months of age, and every six months after one year of age, and continuously followed up to 6 years old, and obtained the child's length/height, weight, and other data. The intensity of the association between pre-pregnancy BMI, GDM, and early AR timing was analyzed by the multivariate logistic regression model. Multiplication and additive models were used to analyze how pre-pregnancy BMI and GDM influenced early AR timing in children. Results: The prevalence of underweight, average weight, overweight, and obesity before pregnancy were 23.2% (672), 66.4% (1 923), 8.7% (251), and 1.7% (50). The prevalence of GDM was 12.4%. We found that 39.3% of children had AR, and the average age at AR was (4.38±1.08). The results of multifactorial logistic regression analysis showed that pre-pregnancy overweight (OR=1.67,95%CI:1.27-2.19), pre-pregnancy obesity (OR=3.05,95%CI:1.66-5.56), and maternal GDM (OR=1.40,95%CI:1.11-1.76) were risk factors for early AR timing in children. In contrast, pre-pregnancy underweight (OR=0.60,95%CI:0.49-0.73) was a protective factor for early AR timing in children. Compared with the different effects of pre-pregnancy overweight/obesity and maternal GDM alone, the combined effect caused a higher risk of early AR timing in children, with OR values (95%CI) were 2.03 (1.20-3.44), 3.43 (1.06-11.12), respectively. The multiplication and additive models showed no interaction between pre-pregnancy BMI and GDM-influenced early AR timing in children. Conclusion: Higher pre-pregnancy BMI and maternal GDM are the independent risk factors for the early AR timing in children, and the co-occurrence of the two is higher risks, but there was no statistical interaction.

[Clinical efficacy evaluation of minimally invasive cardiac surgery coronary artery bypass grafting in patients with multivessel coronary artery disease].

Objective: To investigate the clinical efficacy of minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) in the treatment of patients with multivessel coronary artery disease. Methods: A total of 147 patients with multi-vessel coronary artery disease and coronary heart disease who underwent surgical treatment in Henan Provincial People's Hospital from March 2016 to March 2019 were retrospectively selected. Of which, 69 patients were treated by MICS CABG (minimally invasive group) and 78 patients were treated using the traditional thoracotomy (traditional group). The perioperative indexes, serum myocardial enzyme indexes and renal function indexes of patients before and after operation were compared between the two groups; Two groups of patients were followed up for 2 years; the incidence of adverse cardiovascular events (MACE) was recorded, and survival analysis was performed. Results: The age of the patients in the minimally invasive group and the traditional group were (66.9±5.8) and (68.2±7.0) years old, respectively, and the proportions of males were 60.9% (42 cases) and 51.3% (40 cases) (all P>0.05). All patients in the two groups successfully completed the operation, and no patients in the minimally invasive group were converted to thoracotomy. Before surgery, there was no significant difference in serum cTnI, CK-MB, BUN, Scr, and creatinine clearance between the minimally invasive group and the traditional group (all P>0.05). After re-examination 48 hours after operation, the serum cTnI in the minimally invasive group was (3.109±0.664) µg/L, and the CK-MB was (18.03±3.27) U/L, which were lower than those in the traditional group (3.438±0.715) µg/L, (20.63±4.28) U/L; the difference was statistically significant (all P<0.05). During the 2-year follow-up, there was no statiscally significant difference in the incidence of recurrent myocardial infarction, postoperative atrial fibrillation, postoperative stroke, arrhythmia, heart failure, thrombosis, cardiac death, and MACE events between the minimally invasive group and the traditional group. Statistical significance (all P>0.05). The survival curve analysis showed that the cumulative rates of MACE events in the minimally invasive and traditional groups were 17.39% and 26.92%, respectively (P=0.171). Conclusions: The effect of MICS CABG in the treatment of patients with multivessel coronary artery disease and coronary heart disease is not much different from that of traditional open thoracotomy, but the former is less traumatic, quicker after surgery, and has clinical significance for the recovery of patients' myocardial function.

[Effects of menopause on depressive and anxiety symptoms in community women in Beijing].

Objective: To determine the effects of menopausal stage, age and other associated risk factors on symptoms of anxiety and depression among women in a community in Beijing. Methods: This study was a community-based prospective cohort. Participants who had transitioned through natural menopause, completed two or more depressive and anxiety symptoms evaluations, aged 35 to 64 years, and did not use hormone therapy were selected from the Peking Union Medical College Hospital aging longitudinal cohort of women in midlife to this analysis. The primary outcome variables were depressive and anxiety symptoms, assessed by hospital anxiety and depression scale (HADS). The generalized estimation equation was used in the statistical analysis. Results: Followed up from 2006 to 2014, 430 women and 2 533 HADS assessments were retained in the cohort. Depressive symptoms were more common than anxiety symptoms during all menopausal stages. The incidences of depressive and anxiety symptoms were 14.5% (19/191) and 3.1% (4/191) in the premenopausal -3 stage, respectively. The incidence increased in both menopausal transition and postmenopausal stage, with the highest incidence in the +1c stage [20.6% (155/751) and 8.8% (66/751), respectively]. However, these differences were not statistically significant (all P>0.05). Depressive symptoms were highest in the ≥60-<65 age group [20.8% (74/355)], and anxiety symptoms were highest in the ≥50-<55 age group [8.2% (62/754)]; but there were no statistical significances between different age groups and depressive and anxiety symptoms (all P>0.05). Multivariable analysis showed that high body mass index, low education status, and poor health status were independently associated with depressive symptoms (all P<0.05), and that poor health status, trouble falling asleep, and early awakening were independently associated with anxiety symptoms (all P<0.01). Conclusions: Depressive and anxiety symptoms are more common during menopausal transition and postmenopausal stage compared with reproductive stage. Depressive symptoms are more common than anxiety symptoms. To screen and assess depressive and anxiety symptoms in perimenopausal women is essential, especially for women with high risk factors.

miR-198 regulated the tumorigenesis of gastric cancer by targeting Toll-like receptor 4 (TLR4).

OBJECTIVE: To investigate the role of miR-198 and its target gene Toll-like receptor 4 (TLR4) of tumorigenesis of gastric cancer (GC). MATERIALS AND METHODS: The expression of miR-198 in GC cells was detected by quantitative polymerase chain reaction (qPCR). The proliferation, apoptosis, migration, and invasion of GC cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometry, transwell chamber, and wound scratch assay. Bioinformatics analysis for the results of protein chip was performed to identify the target genes of miR-198. TLR4 was further confirmed to be the target gene of miR-198 by TLR4 luciferase reporter assay. RESULTS: miR-198 expression level in GC SGC-7901 cells significantly decreased compared with the normal cells. When the miR-198 was overexpressed, the proliferation, migration, and invasion of GC cells were significantly decreased, while the apoptosis was increased. The expression of TLR4 in SGC-7901 cells was significantly higher, while the expression of TLR4 in SGC-7901 cells transfected with miR-198 significantly lowered, which was consistent with the Western blot for TLR4. The luciferase reporter assay confirmed that TLR4 was the target genes of miR-198 in GC SGC7901 cells. CONCLUSIONS: miR-198 could induce apoptosis and inhibit the proliferation, migration, and invasion of GC cells through downregulating TLR4 expression.

Effect of a high-concentrate diet on milk components and mammary health in Holstein dairy cows.

In order to evaluate the milk yield, milk quality, and health of dairy cows fed a high-concentrate (HC) diet, eight lactating Holstein dairy cattle were randomly assigned to HC or low-concentrate (LC) diet groups and fed for 50 days, and the auto-control studying before and after treatment with the two diets was used. During the experiment, plasma and milk samples were collected and measured. With regard to milk component, HC feeding led to higher milk production (P < 0.05), but significantly lower milk protein percentage (P < 0.05), milk protein yield (P < 0.05), and milk fat percentage (P < 0.05) throughout the five periods than LC feeding. Milk somatic cell count and N-acetyl-D-glucosaminidase activity (P < 0.01) were higher than those observed under LC feeding. mRNA expression levels of interleukin-8 (IL-8), C-C motif chemokine ligand (CCL5), and lactalbumin alpha (α-LA) were investigated by qPCR and found to be significantly lower (P < 0.01) in cattle fed the HC diet. The amino acid content was analyzed by high performance liquid chromatography (HPLC), and the content of Asp (P < 0.01), Gln (P < 0.01), Ala (P < 0.05), Leu (P < 0.05), Lys (P < 0.05), and Ile (P < 0.01) was significantly lower in the HC group, whereas the content of Arg (P < 0.05) and Phe (P < 0.01) was significantly higher. These results suggest that the HC diet might have an important influence on mammary health. The amino acid content was lower, suggesting that depletion of amino acids, resulting in depleted milk protein, affects milk quality.

[Application of new chest holder in the median sternotomy for open heart surgery in adults].

Objective: To explore the application of new chest holder in the median sternotomy for open heart surgery in adults. Methods: Two hundred adult patients in Henan Provincial People's Hospital from May 2013 to May 2015 were enrolled in the study and randomly divided into two groups. Experimental group included 100 cases who accepted the new type of chest holder in the open heart surgery. Control group were also composed of 100 cases whose sternums were fixed with the pure steel wire cerclage. Sternal closure time was recorded since the sternum closing. All subjects were followed up to obtain the chest incision healing, the incidence of sternal dehiscence, infection and secondary thoracotomy, and thus to estimated the effect of new chest holder. Results: All patients in the experimental group reached the effect of firm closed chest surgery. Sternal closure time of experimental group was much shorter than that of control group[(10±2) vs (21±4) min, P<0.001]. No sternal instability, dehiscence, infection and secondary thoracotomy were found during the follow-up. However, in the control group, 3 secondary thoracotomy cases, 6 sternal dehiscence cases and 2 sternal infection cases were detected. Conclusions: New type of chest holder in the median sternotomy for open heart surgery is more convenient with small surgical trauma. It can also effectively reduce the incidence of sternal instability, dehiscence, infection and secondary thoracotomy.

Intestinal lactic acid bacteria from Muscovy duck as potential probiotics that alter adhesion factor gene expression.

The purpose of this study was to assess the suitability of lactic acid bacteria (LABs) isolated from Muscovy duck as a potential probiotic. Isolates were identified by targeted polymerase chain reaction and assessed in vitro for probiotic characteristics such as autoaggregation; surface-charge; hydrophobicity; tolerance to acidic pH, bile salts and protease; and expression of genes involved in Caco-2 cell adhesion. The LAB isolates exhibited strong resistance to high bile concentration and acidic pH, produced lactic acid, and bacteriostatic (P < 0.05) were identified as bacilli compared with LAB isolates of cocci. Additionally, the LAB isolates showed high sensitivity to penicillin and tetracycline antibiotics, while they were resistant to ofloxacin, Macrodantin, and cotrimoxazole. The level of F-actin mRNA increased in the groups treated with CM3, Salmonella enterica, and CM3 + S. enterica (P < 0.0001, P < 0.05 and P < 0.05 ). The level of cell adhesion molecule (CAM) and E-cadherin (E-cad) mRNA expression was significantly lower in the treatment group (P < 0.05 for both) than in the control. The F-actin, CAM, and E-cad mRNA levels were significantly lower in the S. enterica and CM3 + S. enterica groups (P < 0.01) than in the CM3 group. Among these, RNA levels were higher in the CM3 + S. enterica than S. enterica group. These results indicate that the natural duck gut microflora is an excellent source for probiotic bacteria and can facilitate the establishment of criteria to select probiotic strains for the prevention of diarrhea.

Effect of high-concentrate diet on amino acid transporter expression and milk quality in Holstein dairy cows.

In order to evaluate the effect of high-concentrate diet supplementation on milk protein content, six Holstein dairy cows were assigned into high-concentrate diet (HC) or low-concentrate diet (LC) groups (N = 3/group) for 50 days. With regard to milk protein, HC feeding significantly reduced the percentage of milk protein (P < 0.01), and milk protein yield also reduced. The milk somatic cell count numbers and N-acetyl-D-glucosaminidase activity was significantly higher (P < 0.01) in the HC group than in the LC group. A pre-column derivatization procedure of o-phthalaldehyde was used to analyze the milk amino acid profile, the contents of Asp, Gln, Ala, Ile, Leu, and Lys were significantly lower in milk (P < 0.05), but Arg and Phe were significantly higher (P < 0.05) in the HC group than in the LC group. The mRNA abundance for amino acid transporters SLC7A8, SLC7A10 (P < 0.05), SLC1A3 (P < 0.05), and SLC16A10 (P < 0.05) were decreased in the HC group. These data indicate that expression of amino acid transporters alters regulation of amino acid utilization and decreases milk quality in dairy cows.

Endogenous LPS alters liver GH/IGF system gene expression and plasma lipoprotein lipase in goats.

Endotoxin lipopolysaccharide (LPS) affects the ruminant health and animal performance. The main purposes of this study were to investigate the potential effects of GH/IGF system and lipoprotein lipase (LPL) concentration on resistance the circulating LPS concentration increased in liver with high concentrate diet treatment. Non-lactating goats were randomly allocated to two groups: a high-concentrate diet (HCD) or a low-concentrate diet (LCD) in cross over design and the blood collection at different time points after feeding at the end of the experiment. The average rumen pH was significantly reduced (P<0.05), but the duration with pH was not more than 120 min in the HCD group. The plasma LPL concentration was significantly raised (P<0.05). However, from 2 h onwards, LPS concentration was significantly reduced (P<0.01) in the HCD group compared with LCD group. In addition, the plasma IGF1 concentration and the hepatic insulin-like growth factor-1 receptor (IGF1R) mRNA expression were markedly reduced (P<0.05). However, growth hormone (GH) secretion at 15, 30, and 45 min after feeding and growth hormone receptor (GHR) mRNA expression in the liver was significantly increased (P<0.05) in HCD group. The correlation analysis showed that the plasma LPL concentration was positively correlated with hepatic GHR mRNA expression (P<0.05). Conversely, the plasma LPS concentration was negatively correlated with LPL concentration (P<0.05). These findings reveal that alterations in GH/IGF system function in response to a high-concentrate diet are accompanied by corresponding changes in systemic LPL in non-lactating goats' liver in presence of endogenous LPS stress.

Safety and tolerability evaluation of oral bosentan in adult congenital heart disease associated pulmonary arterial hypertension: a systematic review and meta-analysis.

OBJECTIVES: In this study, we performed a systematic review and meta-analysis of oral bosentan in adult congenital heart disease associated pulmonary arterial hypertension (CHD-PAH) to evaluate its safety and tolerability. MATERIALS AND METHODS: Online electronic database including PubMed, EMBASE and Springer were searched from October 2006 to October 2013 to collect the clinical studies or cohort trials on CHD-PAH with bosentan treatment. Weight Mean Difference (WMD) and Standard Mean Difference (SMD) were used to evaluate the treatment safety and tolerability. Review Manager (RevMan) version 5.0 was performed for the data analysis. RESULTS: Totally 8 studies including 215 patients with CHD-PAH were enrolled in this research. With a period of 3-6 months oral bosentan treatment in patients, there were no significant differences in the scores of resting oxygen saturation (Resting SpO2), post-6-MWT SpO2 after 6-minutes' walktest (6-MWT) and Borg dyspnea index score (BDIs) compared with the baseline; the walking distance on 6-MWT increased significantly. With a period of one year or more oral bosentan treatment, the scores of resting SpO2 and post-6-MWT SpO2 increased significantly; there was no significant difference in BDIs and walking distance on 6-MWT. CONCLUSIONS: The short-term treatment with oral bosentan could increase walking distance on 6-MWT, and long-term treatment could increase the Resting SpO2 in CHD-PAH patients. Oral bosentan in CHD-PAH patients was safe and well tolerated.

Importing, caring, breeding, genotyping, and phenotyping a genetic mouse in a Chinese university.

The genetic manipulation of the laboratory mouse has been well developed and generated more and more mouse lines for biomedical research. To advance our science exploration, it is necessary to share genetically modified mouse lines with collaborators between institutions, even in different countries. The transfer process is complicated. Significant paperwork and coordination are required, concerning animal welfare, intellectual property rights, colony health status, and biohazard. Here, we provide a practical example of importing a transgenic mice line, Dynamin 1 knockout mice, from Yale University in the USA to Perking University in China for studying cell secretion. This example including the length of time that required for paper work, mice quarantine at the receiving institution, and expansion of the mouse line for experiments. The procedure described in this paper for delivery live transgenic mice from USA to China may serve a simple reference for transferring mouse lines between other countries too.

A retrospective study of minipercutaneous laser lithotripsy for treatment of allograft kidney lithiasis obstruction.

OBJECTIVE: To evaluate the safety and effectiveness of invasive percutaneous laser lithotripsy to manage allograft kidney lithiasis obstruction. METHODS: We treated 11 patients with kidney allograft lithiasis with minimally invasive percutaneous nephrolithotomy (mPCNL). RESULTS: All patients treated by mPCNL showed no residual stones thereafter. All subjects recovered successfully without major complications with improved renal function and reduced serum creatinine values. CONCLUSION: mPCNL was safe and effective to treat kidney allograft lithiasis obstruction. We suggest that it may be considered to be a first-line option for this condition.

Effects of maturity stages on the nutritive composition and silage quality of whole crop wheat.

The changes in yields and nutritive composition of whole crop wheat (Triticum aestivum L.) during maturation and effects of maturity stage and lactic acid bacteria (LAB) inoculants on the fermentation quality and aerobic stability were investigated under laboratory conditions. Whole crop wheat harvested at three maturation stages: flowering stage, milk stage and dough stage. Two strains of LAB (Lactobacillus plantarum: LAB1, Lactobacillus parafarraqinis: LAB2) were inoculated for wheat ensiling at 1.0×10(5) colony forming units per gram of fresh forage. The results indicated that wheat had higher dry matter yields at the milk and dough stages. The highest water-soluble carbohydrates content, crude protein yields and relative feed value of wheat were obtained at the milk stage, while contents of crude fiber, neutral detergent fiber and acid detergent fiber were the lowest, compared to the flowering and dough stages. Lactic acid contents of wheat silage significantly decreased with maturity. Inoculating homofermentative LAB1 markedly reduced pH values and ammonia-nitrogen (NH3-N) content (p<0.05) of silages at three maturity stages compared with their corresponding controls. Inoculating heterofermentative LAB2 did not significantly influence pH values, whereas it notably lowered lactic acid and NH3-N content (p<0.05) and effectively improved the aerobic stability of silages. In conclusion, considering both yields and nutritive value, whole crop wheat as forage should be harvested at the milk stage. Inoculating LAB1 improved the fermentation quality, while inoculating LAB2 enhanced the aerobic stability of wheat silages at different maturity stages.

Early demyelination of primary A-fibers induces a rapid-onset of neuropathic pain in rat.

Some types of peripheral neuropathic pain are associated with damage to myelin rather than to axons of primary sensory neurons. It is extremely important to develop selective demyelination animal models for understanding neuropathic pain caused by demyelination. We induced a rapid-onset and reversible demyelination of peripheral A-fibers and neuropathic pain behaviors in adult rats by a single injection of cobra venom into the sciatic nerve. The relation between A-fiber demyelination and the abnormal pain behaviors was investigated using this model. Microfilament recordings revealed that cobra venom selectively blocked A-fibers, but not C-fibers. Selective blockade of A-fibers may result from A-fiber demyelination at the site of venom injection as demonstrated by microscope examination. The axons of the demyelinated A-fibers appeared to be otherwise normal. Neuropathic pain behaviors appeared almost immediately after venom injection and lasted about 3 weeks. Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from both peripheral and central terminals of C-fiber nociceptors. Neurogenic inflammatory responses were also observed in the affected skin via Evan's Blue extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-fiber polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive field.

Comparable efficacy of self-monitoring of quantitative urine glucose with self-monitoring of blood glucose on glycaemic control in non-insulin-treated type 2 diabetes.

AIM: To assess whether self-monitoring of quantitative urine glucose or blood glucose is effective, convenient and safe for glycaemic control in non-insulin treated type 2 diabetes. METHODS: Adults with non-insulin treated type 2 diabetes were recruited and randomized into three groups: Group A, self-monitoring with a quantitative urine glucose meter (n = 38); Group B, self monitoring with a blood glucose meter (n=35); Group C, the control group without self monitoring (n=35). All patients were followed up for six months, during which identical diabetes care was provided. RESULTS: There was a significant decrease in HbA1c within each group (p < 0.05). At the study conclusion, mean changes in HbA1c from baseline were -1.9% for Group A, -1.5% for Group B and -1.0% for Group C, and the proportion of patients achieving HbA1c ≤ 6.5% were 38.9%, 35.3% and 20.0% respectively. However, no significant differences between the groups were found. The average monitoring frequency was significantly higher in Group A than in Group B. The incidence of hypoglycaemia and quality of life scores were similar between the groups. CONCLUSIONS: This study suggests that self-monitoring of urine glucose has comparable efficacy on glycaemic control, and facilitates better compliance than blood self monitoring, without influencing the quality of life or risk of hypoglycaemia.

Isolation and characterization of a novel lectin from the mushroom Armillaria luteo-virens.

From the dried fruiting bodies of the mushroom Armillaria luteo-virens, a dimeric lectin with a molecular mass of 29.4 kDa has been isolated. The purification procedure involved (NH(4))(2)SO(4) precipitation, ion exchange chromatography on DEAE-cellulose, CM-cellulose, and Q-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The hemagglutinating activity of the lectin could not be inhibited by simple sugars but was inhibited by the polysaccharide inulin. The activity was stable up to 70 degrees C but was acid- and alkali-labile. Salts including FeCl(3), AlCl(3), and ZnCl(2) inhibited the activity whereas MgCl(2), MnCl(2), and CaCl(2) did not. The lectin stimulated mitogenic response of mouse splenocytes with the maximal response achieved by 1microM lectin. Proliferation of tumor cells including MBL2 cells, HeLa cells, and L1210 cells was inhibited by the lectin with an IC(50) of 2.5, 5, and 10 microM, respectively. However, proliferation of HepG2 cells was not affected. The novel aspects of the isolated lectin include a novel N-terminal sequence, fair thermostability, acid stability, and alkali stability, together with potent mitogenic activity toward spleen cells and antiproliferative activity toward tumor cells.

Effects of hypoxia and complement activation on lung hemodynamics and fluid exchanges in unanesthetized goats.

The effects of hypoxia and zymosan-activated plasma (ZAP) on lung hemodynamics and fluid exchange were studied in unanesthetized goats. Hypoxia produced a sustained increase in pulmonary arterial pressure (PPA), but had no effect on lung lymph flow and protein content. Following ZAP infusion there was an early phase of leukopenia and marked pulmonary hypertension followed by a phase characterized by a modest increase in the flow of protein-rich lung lymph. When ZAP was infused at a simulated altitude of 4,000 m, there was a further increase in PPA followed by pulmonary vasodilatation, and about 1 h later it was almost back to the control level. No obvious difference in lung lymph flow and protein content was observed between the groups treated with ZAP alone and ZAP plus hypoxia. We conclude that infusion of ZAP into hypoxic animals reduces pulmonary vasoconstriction and that the increase in pulmonary microvascular permeability associated with ZAP is not enhanced by hypoxic conditions occurring at a simulated altitude of 4,000 m.