[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Improved Measurement of the Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

The Relationship between Dietary Copper intake and Telomere Length in Hypertension.

BACKGROUND: More indications proved that diet might be involved in the telomere length, a marker of biological aging and chronic diseases. Copper is widely viewed as one of the essential elements in the diet. Therefore, this study aimed to evaluate the relationship between telomere length and dietary copper intake in hypertension and provide a basis for guiding dietary copper intake in patients with hypertension. METHODS: The data was collected from the National Health and Nutrition Examination Survey (NHANES) in 1999-2000 and 2001-2002. The relevance between telomere length and dietary copper intake in hypertension is assessed using a multivariable linear regression model. RESULTS: We gathered 1,867 participants with hypertension with assessed telomere length and dietary copper intake. We found that one unit increasing log-transformed dietary copper intake in hypertension was significantly associated with longer telomere length base pair (bp) (ß = 112.20, 95% confidence interval [CI]: 5.48, 218.92), after controlling for covariates, including age, sex, ethnicity, body mass index (BMI), physical activity, and taking medication for hypertension. For the age group, we found that one unit increasing log-transformed dietary copper in hypertension was associated with longer telomere length (ß = 237.95, 95% CI: 114.39, 361.51) in the age group >45 years. The grouping was based on whether the participants take medication for hypertension. We found that one unit increasing log-transformed dietary copper in hypertension was associated with longer telomere length (ß = 116.47, 95% CI: 0.72, 232.21) in the group that takes medication for hypertension. CONCLUSIONS: This study demonstrates that dietary copper intake was associated with longer telomere length in patients with hypertension, which provides evidence for guiding dietary copper intake in patients with hypertension. However, further studies are needed to evaluate the effect of copper supplementation on telomere length in patients with hypertension in well-designed random control studies and prospective studies.

A longitudinal histologic evaluation of vitamin D receptor expression in the skeletal muscles of patients with a distal radius fracture.

We investigated the effect of vitamin D supplementation on the expression of muscle vitamin D receptor (VDR) and cross-sectional area (CSA) in patients with a distal radius fracture (DRF). Significant increases in VDR expression and CSA were observed, especially in vitamin D-deficient patients. PURPOSE: Vitamin D supplementation is known to enhance muscle mass and function, but whether the VDR is essential in this process remains unknown. We evaluated the change in VDR expression and CSA in the forearm muscles following vitamin D supplementation in patients with a DRF. METHODS: We prospectively recruited 18 women with a median age of 63.5 years who have a DRF. We obtained two biopsies of the forearm muscle, first at the time of fracture repair and then during hardware removal. We supplemented 1000 IU of vitamin D per day during a median interval of 8 months. We examined the changes in VDR expression and CSA by immunohistochemistry. RESULTS: The median serum 25-hydroxyvitamin D [25(OH)D] increased from 14.3 to 32.1 ng/mL (P = 0.001). The median VDR expression increased from 0.72 to 0.78 (P = 0.002), and the median CSA increased from 1290.0 to 1685.8 µm2 (P = 0.022). Significant increases in VDR expression and CSA were observed in vitamin D-deficient patients [25(OH)D] < 20 ng/mL, but not in vitamin D-non-deficient patients. The changes in VDR expression and CSA were in the same direction in 13 patients, but in the opposite direction in 5 patients. CONCLUSION: Vitamin D supplementation may increase muscle VDR expression and CSA in patients with a DRF, especially in vitamin D-deficient patients. The increase in CSA without an increase in VDR expression in some patients indicates that the effect of vitamin D supplementation on muscle mass could be mediated by indirect effect of serum vitamin D restoration and by VDR.

Effects of laying breeder hens dietary ß-carotene, curcumin, allicin, and sodium butyrate supplementation on the jejunal microbiota and immune response of their offspring chicks.

Our long-term goal is to improve chick health and reduce the use of antibiotics in the poultry industry via maternal effects. To link jejunal microbes with chicks' different immune levels and growth performance in our previous research, this study investigated jejunal microbes, jejunal inflammation, and immune responses based on a comparison between different groups. Newly hatched Hy-Line chicks were allotted into 3 groups: a chick control group (cCON), a ciprofloxacin lactate treatment group (Cipro)-the chicks of the cCON and Cipro groups were hatched from laying breeder hens given a basal diet-and a 5-wk ß-carotene, curcumin, allicin, and sodium butyrate supplementation group (cCCAB), wherein chicks hatched from laying breeder hens. All groups were fed the same diet for 4 wk; the Cipro group was given ciprofloxacin lactate in drinking water continuously. At the end of the experiment, the results demonstrated that the jejunal microbes of the Cipro group showed significant changes in alpha and beta diversity, and in taxonomy at phylum and genus levels. Statistically, a total of 67 significantly enriched (P < 0.05) taxa were identified between groups by linear discriminant analysis effect size; Firmicutes was significantly enriched (P < 0.05) in the cCCAB group, 65 taxa were significantly enriched (P < 0.05) in the Cipro group, and 32 of the 65 enriched (P < 0.05) taxa were in the Proteobacteria phylum of the Cipro group. Levels of lipopolysaccharide in jejunal content, and nuclear factor kappa-B, and tumor necrosis factor-α in jejunums of the Cipro and cCCAB groups were increased (all P < 0.05) compared to those in the cCON group. There was obvious neutrophil infiltration and upregulated (all P < 0.05) IL-6 mRNA in the Cipro group jejunums compared to the cCON and cCCAB groups. The expression of PSME3 and PSME4 genes was upregulated (all P < 0.05) in the cCCAB group compared to the cCON and Cipro groups. In conclusion, ciprofloxacin lactate administration led to potential hazards in health and growth in chicks via microbial disturbances-induced jejunal inflammation, and laying breeder hens dietary supplementation with ß-carotene, curcumin, allicin, and sodium butyrate could enhance jejunal immunity of their offspring via the interaction between host innate immunity selected microbial colonization and microbiota educated adaptive immunity.

Effects of laying breeder hens dietary ß-carotene, curcumin, allicin, and sodium butyrate supplementation on the growth performance, immunity, and jejunum morphology of their offspring chicks.

This study evaluated the growth performance, immunity, and jejunum morphology of chicks hatched from laying breeder hens given dietary additive supplementation, as well as chicks receiving direct antibiotic supplementation in early life. Hy-line breeder hens were allotted to 2 groups with 3 replicates. A control group (CON) was fed a basal diet, and the treatment group (CCAB) received ß-carotene, curcumin, allicin, and sodium butyrate in addition to basal diet for 5 wk. Breeder-hen eggs were collected and hatched. The chicks hatched from the CON group were assigned to 2 treatments: a chick control group (cCON) and a chick treatment group (Cipro) given ciprofloxacin lactate into drinking water; the cCON group, Cipro group, and the chicks hatched from the CCAB group (cCCAB) were fed the same diet for 4 wk. The results demonstrated that there were significant differences between the CON and CCAB groups in the serum levels of IgA, IgG, IgM (triple P < 0.01), lysozyme (P < 0.05), and ß-defensin (P < 0.05). The body weights of the cCCAB group's chicks increased at 1, 7, and 28 D of age (P < 0.05, P < 0.05, P < 0.01, respectively), and those of the Cipro group's chicks increased at 7 and 21 D of age (P < 0.01, P < 0.05). The tibial lengths of the cCCAB group's chicks increased at 1, 7, 14, 21, and 28 D of age (P < 0.01, P < 0.05, triple P < 0.01), and the lengths in the Cipro group increased at 7 and 14 D of age (P < 0.01, P < 0.01). Intestinal development, including intestinal length, jejunum morphology, and IgA positive cells, helps to explain these results. The breeder eggs from the CCAB group had higher IgG (P < 0.05) and IgM (P < 0.05) levels in the egg whites and higher IgA, IgG, and IgM levels (triple P < 0.01) in the egg yolks. In conclusion, ß-carotene, curcumin, allicin, and sodium butyrate supplementation of laying breeder hen diets produced more advantages in growth performance and intestinal development in offspring than in chicks directly supplemented with antibiotics.

Coagulation in hindbrain membrane meningioma patients treated with different injections using acute hypervolemic hemodilution.

The aim of this study was to analyze the changes in coagulation in meningioma patients treated with different injections using the method of acute hypervolemic hemodilution (AHH). One hundred fifty hindbrain membrane meningioma patients were randomly divided into 5 groups, 30 per group. The first group were injected 40ml/time with Danhong after anesthesia induction; the second group were injected with 40ml~60ml/time Kangai and combined with interventional chemotherapy and embolization procedure; the third group of AHH were injected with polygeline 15ml/kg; the fourth group were injected with hydroxyethyl starch (130/0.4) sodium chloride in doses of 15ml/kg; the control group underwent basic treatment for lowering blood pressure and lowering blood fat. The changes of coagulation index were recorded before and after surgery and before and after the injection of different medications. Compared to the control group, for the first group of AHH, after being treated for 10 days and 30 days, the concentrations of bone specific alkaline phosphatase (BALP), bone Gla protein (BGP) and pro-collagen carboxy-terminal propeptide (PICP) were higher than that of the control group, the levels of endotoxin (ET) and C-reactive protein (CRP) were decreased compared to the control group (p less than 0.05); for the second group of AHH, after being treated for 10 days, the index of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg) were not significantly changed, but the related level of vascular endothelial growth factor (VEGF) significantly decreased (p less than 0.05). Comparing the coagulation function index after surgery in the third and fourth groups, there were no significant changes in mean arterial pressure (MAP) level, heart rate (HR) value presented a low decrease, central venous pressure (CVP) level increased and the level of interleukin IL-6 showed a steady state after increasing. Analyzing the levels of interleukin IL-8 and tumor necrosis factor-α (TNF-α) after surgery, it was seen that in the third group they increased and in the fourth group they decreased (p less than 0.05). Danhong injection improved the coagulation function and microcirculation of patients, Kangai injection and interventional chemotherapy and embolization restrained the appearance of tumor angiogenesis, AHH operation with polygeline injection and hydroxyethyl starch (130/0.4) sodium chloride kept blood flow in normal parameters.

Lack of mature lymphocytes results in obese but metabolically healthy mice when fed a high-fat diet.

BACKGROUND/OBJECTIVES: Obesity is characterized by chronic inflammation and immune dysregulation, as well as insulin resistance, but the link between obesity and adaptive immunity remains to be fully studied. METHODS: To elucidate the role of adaptive immunity on body composition, glucose homeostasis and inflammation, recombination-activating gene 1 knockout (Rag1-/-) mice, without mature T-lymphocytes or B-lymphocytes, were maintained on a low- or high-fat diet (LFD and HFD, respectively) for 11 weeks. RESULTS: Rag1-/- mice fed HFD gained significantly more weight and had increased body fat compared with wild type. Downregulation of energy expenditure as well as brown fat uncoupling protein UCP-1 and UCP-3 gene expression were noticed in HFD-fed Rag1-/- mice compared with LFD. HFD mice had significantly decreased energy intake compared with LFD mice, consistent with decreased agouti-related protein and increased pro-opiomelanocortin gene expression levels in the hypothalamus. Moreover, compared with wild type, Rag1-/- mice had lower interleukin (IL)-4 levels, a cytokine recently found to induce browning in white adipocytes, and higher IL-12 levels in HFD-fed Rag1-/- mice. Despite that HFD Rag1-/- mice were more obese, they had similar glucose, insulin and adiponectin levels, while leptin was marginally increased. CONCLUSIONS: Mice with deficiency in adaptive immunity are obese, partly owing to decreased energy expenditure, but are metabolically normal, suggesting that mature lymphocytes have necessary roles in the development of obesity-related metabolic dysregulation.

Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus (MRSA) RN4220/pUL5054 and inhibition of MRSA pyruvate kinase.

Increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) worldwide with limited therapeutic options is a growing public health concern. Natural products have been shown to possess antibacterial actions against MRSA. Flavonoids from natural products have been shown to possess antibacterial actions against MRSA by antagonizing its resistance mechanisms. Diosmin and diosmetin are natural flavonoids found in a variety of citrus fruits. The aim of this study was to investigate whether diosmin and diosmetin could inhibit the growth of MRSA and the in vitro enzymatic activity of a newly discovered MRSA drug target, pyruvate kinase (PK). By using a panel of MRSA strains with known resistant mechanisms, neither diosmin nor diosmetin was shown to possess direct antibacterial activities against all tested MRSA strains. However, in checkerboard assay, we found that diosmetin together with erythromycin, could synergistically inhibit the growth of ABC-pump overexpressed MRSA-RN4220/pUL5054, and time kill assay also showed that the antibacterial activities of diosmetin with erythromycin were bactericidal. Diosmetin was further shown to significantly suppress the MRSA PK activities in a dose dependent manner. In conclusion, the inhibition of MRSA PK by diosmetin could lead to a deficiency of ATP and affect the bacterial efflux pump which might contribute to the antibacterial actions of diosmetin against MRSA.

4-Aminobiphenyl downregulation of NAT2 acetylator genotype-dependent N- and O-acetylation of aromatic and heterocyclic amine carcinogens in primary mammary epithelial cell cultures from rapid and slow acetylator rats.

Aromatic and heterocyclic amine carcinogens present in the diet and in cigarette smoke induce breast tumors in rats. N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2) enzymes have important roles in their metabolic activation and deactivation. Human epidemiological studies suggest that genetic polymorphisms in NAT1 and/or NAT2 modify breast cancer risk in women exposed to these carcinogens. p-Aminobenzoic acid (selective for rat NAT2) and sulfamethazine (SMZ; selective for rat NAT1) N-acetyltransferase catalytic activities were both expressed in primary cultures of rat mammary epithelial cells. PABA, 2-aminofluorene, and 4-aminobiphenyl N-acetyltransferase and N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine and N-hydroxy-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline O-acetyltransferase activities were two- to threefold higher in mammary epithelial cell cultures from rapid than slow acetylator rats. In contrast, SMZ (a rat NAT1-selective substrate) N-acetyltransferase activity did not differ between rapid and slow acetylators. Rat mammary cells cultured in the medium supplemented 24 h with 10muM ABP showed downregulation in the N-and O-acetylation of all substrates tested except for the NAT1-selective substrate SMZ. This downregulation was comparable in rapid and slow NAT2 acetylators. These studies clearly show NAT2 acetylator genotype-dependent N- and O-acetylation of aromatic and heterocyclic amine carcinogens in rat mammary epithelial cell cultures to be subject to downregulation by the arylamine carcinogen ABP.

Optic nerve changes in zinc-deficient rats.

In this study the optic nerve changes in zinc (Zn)-deficient rats are examined. Zinc is one of the essential trace elements and is known to be related to optic nerve diseases such as ethambutol neuropathy. However, the effect of Zn on the optic nerve has not been studied experimentally in animals. We used 3 week old weanling male Wistar Kyoto rats weighing 40-50 g. Rats were fed a Zn-deficient diet containing 0.007 mg of Zn per 100 g, all other nutrients and distilled and deionized water. The same water supplemented with 3 mg Zn per 100 g was given to the control group. After 4 or 7 weeks on a Zn-deficient diet, the optic nerve was examined with an electron microscope. A recovery group was fed a Zn-containing diet for 5 weeks after 7 weeks on the Zn-deficient diet. The serum Zn levels of the deficient group were significantly decreased at both 4 and 7 weeks. Most of the Zn-deficient rats showed hair loss around the eyes and on the extremities. Ultrastructural findings were as follows. The number of myelinated axons of Zn-deficient rats at 4 and 7 weeks were significantly decreased and the myelin sheaths were significantly thinner in the Zn-deficient groups and in the recovery group. Unmyelinated axons were more numerous than in the control rats. Destruction of myelin and proliferation of glial cells were found in the optic nerves of Zn-deficient rats. This study suggests that the optic nerve needs Zn for the maintenance of its cell structure and even if Zn is supplied to the Zn-deficient rats, destruction of the myelin structure may continue. Zn-deficiency induce a decrease of myelinated nerve fibers, and it is thought that optic neuropathy in patients treated with some drugs such as ethambutol may be a secondary change due to Zn-deficiency following drug administration.

[Effects of cordyceps sinensis on T lymphocyte subsets and hepatofibrosis in patients with chronic hepatitis B].

In order to find an effective drug to cure patients with chronic hepatitis B, cordyceps sinensis had been used to treat 25 patients with chronic hepatitis B. The comprehensive index, including T lymphocyte subsets (CD4, CD8), hyaluronic acid(HC) and precollagen type III(PC III), were observed before and after treatment. After 3 months of treatment, CD4 and CD4/CD8 ratio increased significantly(P < 0.05), while HA and PC III decreased significantly(P < 0.05) compared with the control. The results suggest that the beneficial effects might be obtained by using cordyceps sinensis to adjust the T lymphocyte subsets level and to treat hepatic fibrosis on patients with chronic hepatitis B.

[Preventive and therapeutic effects of calcium lactate on osteoporosis in aged ovariectomized rats].

Twelve-month-old rats were ovariectomized (OVX), remained untreated for one month. Calcium lactate was given daily by gavage at the dose of 125, 250 and 750 mg/kg(Ca125, Ca250, Ca750) for 3 months. The results showed that compared with OVX rats, Ca250 could markedly increase the bone mineral density (BMD) at right femur. Both Ca250 and Ca750 could markedly enhance the ash weight, ratio of ash weight to dry weight of left femur and ratio of 24-hour urinary Ca/Cr. Ca125 could markedly decrease serum ALP concentration. Both Ca125 and Ca250 could decrease the ratio of 24-hour urinary Hop/Cr. All doses of calcium lactate groups could elevate serum Ca, and were no influence on the volume, wet and dry weight of the left femur and serum OC levels. In conclusion, the administration of calcium lactate to aged OVX rats prevents bone resorption, and its mechanism may be relating to the supplement of calcium properly.

Effect of electrochemical therapy on immune functions of normal and tumour-bearing mice.

The effect of electrochemical therapy (ECT) on immune functions of normal and tumour-bearing mice was studied. In normal mice, ECT had no obvious effect on delayed type hypersensitivity (DTH) or on the mononuclear phagocytic system, but significantly reduced the production of agglutinin antibodies. In tumour-bearing mice, ECT enhanced the DTH reaction, increased the production of agglutinin antibodies and enhanced the clearance of Congo red. In conclusion, in tumour-bearing mice, ECT enhanced both cellular immune functions of T- and B-lymphocytes and non-specific immune functions of the phagocytic system.

Diagnostic efficacy of a nasotracheal protected specimen brush in patients with suspected bacterial pneumonia.

The diagnostic yield and safety of a novel nasotracheal protected specimen brush (PSB) were evaluated in 15 nonintubated adult patients with suspected bacterial pneumonia. A double-catheter PSB was passed directly through the anesthetized nose and into the trachea without bronchoscopy or fluoroscopy. Endotracheal brushing was performed in less than 10 sec, and the brush was immediately processed for Gram staining and quantitative aerobic and anaerobic cultures. According to clinical follow-up and response to therapy, 11 episodes of bacterial pneumonia and five cases of nonbacterial lung disease were established. The PSB Gram stain confirmed lower respiratory sampling in all cases. The PSB cultures indicated respiratory pathogens in 9/11 (82%) cases of pneumonia, with greater than 10(3) colony-forming units (cfu)/ml in all but two specimens. All patients with pneumonia responded to specific antibiotics. All patients with nonbacterial disorders had PSB cultures of less than 10(3) CFU/ml, and their pulmonary processes improved without antibiotic therapy. The procedure was well tolerated, although two patients had transient bronchospasm or apnea. Experience with the nasotracheal PSB is limited, but the procedure appears to be a reliable and relatively safe alternative diagnostic method in selected patients with suspected bacterial pneumonia. Quantitative cultures are necessary to improve its diagnostic accuracy.

[Regional distribution of liver cancer and its relation to selenium levels in Qidong County, China].

The selenium (Se) level in barley and maize from 43 communes of Qidong county, a high risk area of liver cancer in China, were assayed. An inverse correlation between the Se level and the liver cancer incidence was observed. An inverse correlation was also observed between the blood Se level and liver cancer incidence of the local residents. When selenite solution was sprayed on the crops during their preflowering, the content of Se in barley and maize was increased by 6 fold over the control. It is suggested that the increase of blood Se level of the residents who live in the low-Se areas by this method be useful in the prevention of liver cancer.

Bronchodilator effects of caffeine in coffee. A dose-response study of asthmatic subjects.

Although caffeine is a universal drug and has multiple pharmacologic and physiologic actions in man, there are surprisingly few objective data about its effect on pulmonary function. We conducted a short-term, double-blind, randomized crossover study in nine asthmatic adults who ingested decaffeinated coffee containing varying amounts of added caffeine (mean of 0.2,2.5,5.6, and 7.2 mg/kg of body weight) on different days. The subjects also ingested decaffeinated coffee and aminophylline (200 mg) on a separate day of study. Baseline and post-drug determinations of serum levels of caffeine and theophylline, forced expired volume and flow, specific airway conductance (Gaw/VL), vital signs, and reported symptoms were obtained. Peak increases in serum caffeine concentrations (mean, 12.4 micrograms/ml +/- 1.5 micrograms/ml) occurred 45 minutes following the highest dose of caffeine (7.2 mg/kg), whereas the peak theophylline level (mean 3.8 micrograms/ml +/- 0.4 micrograms/ml) occurred 90 minutes following oral administration of aminophylline (mean theophylline, 2.6 mg/kg). Comparable peak increases in the forced expiratory volume in one second (FEV1), the forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%), and Gaw/VL occurred at 120 minutes following aminophylline and the highest dose of caffeine, indicating that caffeine is an effective bronchodilator but is only 40 percent as active as an equivalent molar dose of theophylline. Regression analysis revealed statistically significant dose-response relationships between peak increases in serum caffeine concentrations and increases in FEV1, FEF25-75%, and Gaw/VL from baseline values. These findings have diagnostic and therapeutic implications regarding the use of caffeine prior to tests of pulmonary function and as a dietary agent, alone or in combination with theophylline.

Regional variation of cancer mortality incidence and its relation to selenium levels in China.

The epidemiological relationship between selenium level and age-adjusted human cancer mortality (incidence) was studied in 24 regions located in eight provinces of China. Statistically significant inverse correlation was found between age-adjusted total cancer death rates and selenium levels in whole blood from local residents. In the areas with high selenium levels, there was significantly lower mortality in both males and females from cancer of the stomach and esophagus. In addition, an inverse correlation between regional distribution of liver cancer incidence and selenium contents in blood and grains in Qidong county, an area with high risk of hepatoma, was observed. With the intention of providing selenium supplements to residents living in low selenium regions, the selenium content in grains was raised by means of foliar spraying of crops with Na2SeO3 solution.