The Positive and Negative Effects of Calcium Supplementation on Mortality in Septic ICU Patients Depend on Disease Severity: A Retrospective Study from the MIMIC-III.

Background: Calcium administration in septic patients with hypocalcemia is a controversial issue. The present study preliminarily investigated the effects of calcium supplementation on the length of hospitalization and mortality in septic ICU patients with different severities of hypocalcemia and disease. Method: A total of 5761 eligible septic patients, including 2689 who received calcium supplementation and 3072 who did not receive calcium supplementation, were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The cofounding covariates between the calcium supplement and nonsupplement groups were balanced using the propensity score matching model. We compared the length of stay (LOS) in the ICU and hospital with 28-day and hospital mortality and stratified the analysis according to the sequential organ failure assessment (SOFA) score and ionized calcium (iCa) at the first ICU admission in the matched groups. Results: The results showed that iCa at the first ICU admission was associated with mortality in sepsis patients (HR: 0.421; 95% CI: 0.211∼0.837), but the lowest mortality rate was observed in patients with mild hypocalcemia. A total of 993 paired patients were included in the analysis after propensity score matching. Regardless of the SOFA score or presence of iCa, the LOS in the ICU was higher in the calcium supplement group than in the nonsupplement group. The survival analysis was stratified by the SOFA score and showed that calcium supplementation reduced mortality when the patient's SOFA score was ≥8 (p=0.002), and it worsened the outcome when the patient's SOFA score was ≤4 (p=0.010). It had no significant effect on patients with SOFA scores ranging from 5 to 7 (p=0.911). Conclusion: Our results showed that mild hypocalcemia may be protective in septic patients, and calcium supplementation may have positive and negative effects on mortality depending on disease severity. The SOFA score may be a valuable clinical index for decisions regarding calcium administration.

The dietary arachidonic acid improved growth and immunity of honey bee (Apis mellifera ligustica).

Honeybees cannot synthesize arachidonic acid (ARA) themselves, only obtain it from food. Most pollen is deficient or contains a small amount of ARA. The necessity of supplementary ARA in bees' diet has not been studied. The objective of this study was to investigate the effects of dietary ARA levels on the growth and immunity of Apis mellifera ligustica. A total of 25 honeybee colonies were randomly assigned to five dietary groups which were fed basic diets supplemented with 0, 2, 4, 6, and 8% of ARA. The diet with 4% ARA improved the body weight of newly emerged worker bees compared with the control group. Supplement of ARA in honeybee diets changed the fatty acid composition of honeybee body. SFA and MUFA contents of bees' body declined, and PUFA content rised in the ARA group. Compared with the control group, the supplement of ARA in honeybee diets increased the contents of ARA, C22:6n-3 (DHA) and C18:3n-6 in bees' body significantly, but decreased the contents of C16:1 and C18:3n-3. The diet supplied with 4% ARA reduced the mortality rate of honeybee infected with Escherichia coli. The activity of immune enzymes (phenoloxidase, antitrypsin, and lysozyme) and the mRNA expression levels of immune genes (defensin-2, toll, myd88, and dorsal) were improved by ARA diets to varying degrees depending on the ARA levels, especially 4% ARA. These results suggested that dietary ARA could improve the growth, survival, and immune functions of honeybees. Supplement of ARA in bees' diet would be valuable for the fitness of honeybees.

[Blood biochemical indexes in ED patients with kidney deficiency or non-kidney deficiency: A comparative analysis of 156 cases].

OBJECTIVE: To analyze the blood biochemical characteristics of the ED patients with different types of kidney deficiency or non-kidney deficiency. METHODS: We reviewed the clinical data on 156 ED patients treated in our Department of Andrology from May to July 2018 and, according to the traditional Chinese medicine (TCM) syndromes, divided them into four groups: kidney-yang deficiency (n = 48), kidney-yin deficiency (n = 34), kidney-yin+yang deficiency (n = 36) and non-kidney deficiency control (n = 38). We obtained and compared their blood biochemical indexes, including the levels of testosterone (T), estradiol (E2), cortisol (CORT), thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), nitric oxide (NO), total nitric oxide synthase (tNOS), and inducible nitric oxide synthase (iNOS). RESULTS: There were no statistically significant differences in the mean age, course of disease, IIEF-5 score and erection hardness score (EHS) among the four groups of patients. Pairwise comparison showed that, compared with the non-kidney deficiency controls, the patients in the kidney-yin deficiency group exhibited a dramatically higher level of CORT (ï¼»87.97 ± 45.59ï¼½ vs ï¼»121.78 ± 41.87ï¼½ µg/L, P = 0.002) and those in the kidney-yang deficiency group a remarkably lower level of FT3 (ï¼»5.44 ± 0.38ï¼½ vs ï¼»5.11 ± 0.54ï¼½ pmol/L, P = 0.008). The iNOS level was significantly higher in the kidney-yin deficiency group (14.42 ± 2.49 U/ml) than in either the control (12.71 ± 2.58 U/ml) (P = 0.039) or the kidney-yang deficiency group (13.05 ± 2.17 U/ml) (P =0.049). CONCLUSIONS: ED patients with different types of kidney deficiency syndromes have different blood biochemical indexes, which may help clarify the biological basis of the TCM syndromes of kidney deficiency in ED patients.

Hypocalcemia in sepsis: analysis of the subcellular distribution of Ca2+ in septic rats and LPS/TNF-α-treated HUVECs.

INTRODUCTION: Hypocalcemia has been widely recognized in sepsis patients. However, the cause of hypocalcemia in sepsis is still not clear, and little is known about the subcellular distribution of Ca2+ in tissues during sepsis. METHODOLOGY: We measured the dynamic change in Ca2+ levels in body fluid and subcellular compartments, including the cytosol, endoplasmic reticulum and mitochondria, in major organs of cecal ligation and puncture (CLP)-operated rats, as well as the subcellular Ca2+ flux in HUVECs which treated by endotoxin and cytokines. RESULTS: In the model of CLP-induced sepsis, the blood and urinary Ca2+ concentrations decreased rapidly, while the Ca2+ concentration in ascites fluid increased. The Ca2+ concentrations in the cytosol, ER, and mitochondria were elevated nearly synchronously in major organs in our sepsis model. Moreover, the calcium overload in CLP-operated rats treated with calcium supplementation was more severe than that in the non-calcium-supplemented rats but was alleviated by treatment with the calcium channel blocker verapamil. Similar subcellular Ca2+ flux was found in vitro in HUVECs and was triggered by lipopolysaccharide (LPS)/TNF-α. CONCLUSIONS: Ca2+ influx from the blood into the intercellular space and Ca2+ release into ascites fluid may cause hypocalcemia in sepsis and that this process may be due to the synergistic effect of endotoxin and cytokines.

Highly Sensitive Flexible Iontronic Pressure Sensor for Fingertip Pulse Monitoring.

The pulse is a key biomedical signal containing various human physiological and pathological information highly related to cardiovascular diseases. Pulse signals are often collected from the radial artery based on Traditional Chinese Medicine, or by using flexible pressure sensors. However, the wrist wrapped with a flexible pressure sensor exhibits unstable signals under hand motion because of the concave surface of the wrist. By contrast, fingertips have a convex surface and therefore show great promises in stable and long-term pulse monitoring. Despite the promising potential, the fingertip pulse signal is weak, calling for highly sensitive detecting devices. Here, a highly sensitive and flexible iontronic pressure sensor with a linear sensitivity of 13.5 kPa-1 , a swift response, and remarkable stability over 5000 loading/unloading cycles is developed. This sensor enables stable and high-resolution detection of pulse waveform under both static condition and finger motion. Fingertip pulse waveforms from subjects of different genders, age, and health conditions are collected and analyzed, suggesting that fingertip pulse information is highly similar to that of the radial artery. This work justifies that fingertip is an ideal platform for pulse signals monitoring, which would be a competitive alternative to existing complex health monitoring systems.

Sodium Selenium Enhances the Antioxidative Activities and Immune Functions of Apis mellifera (Hymenoptera: Apidae) and Increases the Selenium Content in Royal Jelly.

Selenium (Se), as an essential micronutrient, has been demonstrated to play an important role in life activities. In this study, we studied the effects of sucrose solutions containing sodium selenite on Apis mellifera (L.). We obtained the appropriate level of sodium selenite for A. mellifera by determining the life span by lab rearing, and then, we studied the effects of sodium selenite on antioxidant activity, phenol oxidase activity, development of the hypopharyngeal gland, Se content of body tissues and royal jelly (RJ), and related gene transcription levels for a bee colony. The results of lab rearing showed that a concentration of 0.57 mg/liter sodium selenium could extend life. After feeding the colony sodium selenium at concentrations of 0.3 mg/liter and 0.6 mg/liter, the results showed that 0.6 mg/liter sodium selenite could enhance the antioxidant and immune activity of 6-d-old larvae and 1-d-old and 9-d-old worker bees (P < 0.05), increase the Se content of body tissues (P < 0.05) and RJ (P < 0.05), and improve the expression of related genes (P < 0.05).

Icariside II Promotes the Differentiation of Adipose Tissue-Derived Stem Cells to Schwann Cells to Preserve Erectile Function after Cavernous Nerve Injury.

Icariside II (ICA II) is used in erectile dysfunction treatment. Adipose tissue-derived stem cells (ADSCs) are efficient at improving erectile function. This study aimed to explore the action mechanism of ADSCs in improving erectile function. ADSCs were isolated from the adipose tissues of rats. Cell proliferation was determined using the Cell Counting Kit-8 (CCK-8) assay. The expressions of mRNA and protein were determined separately through qRT-PCR and western blot. The endogenous expressions of related genes were regulated using recombinant plasmids and cell transfection. A Dual-Luciferase Reporter Assay was performed to determine the interaction between miR-34a and STAT3. Rat models with bilateral cavernous nerve injuries (BCNIs) were used to assess erectile function through the detection of mean arterial pressure (MAP) and intracavernosal pressure (ICP). ICA II promoted ADSCs' proliferation and differentiation to Schwann cells (SCs) through the inhibition of miR-34a. Suppressed miR-34a promoted the differentiation of ADSCs to SCs by upregulating STAT3. ICA II promoted the differentiation of ADSCs to SCs through the miR-34a/STAT3 pathway. The combination of ICA II and ADSCs preserved the erectile function of the BCNI model rats. ADSCs treated with ICA II markedly preserved the erectile function of the BCNI model rats, which was reversed through miR-34a overexpression. ICA II promotes the differentiation of ADSCs to SCs through the miR-34a/STAT3 pathway, contributing to erectile function preservation after the occurrence of a cavernous nerve injury.

Discovery of novel bacterial elongation condensing enzyme inhibitors by virtual screening.

The elongation condensing enzymes in the bacterial fatty acid biosynthesis pathway represent desirable targets for the design of novel, broad-spectrum antimicrobial agents. A series of substituted benzoxazolinones was identified in this study as a novel class of elongation condensing enzyme (FabB and FabF) inhibitors using a two-step virtual screening approach. Structure activity relationships were developed around the benzoxazolinone scaffold showing that N-substituted benzoxazolinones were most active. The benzoxazolinone scaffold has high chemical tractability making this chemotype suitable for further development of bacterial fatty acid synthesis inhibitors.

[Protective effects of puerarin on 60Co-gamma-induced acute injury of sertoli cells of testis in mice].

OBJECTIVE: To study the protective effects of puerarin on 60Co-y-induced acute injury of sertoli cells of testis in mice and the mechanisms for its radiation protection. METHODS: Forty male Wistar mice were randomly divided into four groups, i. e., the normal group, the model group, the low dose puerarin group, and the high dose puerarin group, respectively, 10 in each. The lower abdomen and scrotal area of mice were irradiated with a single dose of 8 Gy 60Co-gamma ray for 517 s in the model and two puerarin groups. Twenty-four h after modeling, different concentrations of puerarin (at the daily dose of 230 and 450 mg/kg respectively) were given to mice in the low and high dose groups by gastrogavage, once daily for two successive weeks. Equal volume of physiological saline was given to mice in the normal group and the model group, once daily for two successive weeks. The morphology of the testicular tissues was observed. The levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and inhibin beta were determined by ELISA. The relative expressions of Inhibin beta mRNA in the testicular tissues were determined by Real-time quantitative PCR. RESULTS: Sertoli cells and spermatogenic cells were injured at different degrees in the model group. They were improved in the low and high dose puerarin groups, more obviously in the high dose puerarin group. Compared with the normal group, the level of serum FSH in the model group was significantly improved, while the serum level of Inhibin beta and the expression of Inhibin beta mRNA obviously decreased, showing statistical difference (P<0.05). Compared with the model group, the levels of serum FSH, Inhibin beta, and the expression of Inhibin beta mRNA were significantly improved in the low and high dose puerarin groups (P<0.05), more obviously in the high dose puerarin group (P<0.01, P<0.05). CONCLUSION: Chinese medicine monomer of puerarin had certain protective effects on 60Co-gamma-induced acute injury of Sertoli cells in mice.

[Chinese medicinal monomer and compound for 60Co-gamma-induced spermatogenic disturbance in mice].

OBJECTIVE: To explore the effects of the monomer and compound of the Chinese herbal drugs resveratrol, lycium barbarum polysaccharide (LBP) and icariin on 60Co-gamma-induced spermatogenic disturbance in mice based on the theory of modern Chinese medicine. METHODS: A total of 105 male Kunming mice were randomly divided into seven groups, with 15 in each. Group A were normally raised and Groups B, C, D, E, F and G irradiated by 60Co-gamma 6 Gy followed by 60Co-gamma 4 Gy at the interval of 7 days. A week later, Groups C, D, E, F and G received intragastrically the suspension of resveratrol, resveratrol + LBP, resveratrol + icariin, resveratrol + LBP + icariin and resveratrol + LBP + icariin + L-carnitine, respectively, at the dose of 80 mg/(kg x d) for 60 days. The general condition, physical signs and body weight changes of the mice were recorded, and 24 hours after the intragastric medication, their testes were harvested to obtain the testicular weight and indexes, the levels of FSH, LH, T and E2 determined by ELISA, the T/E2 ratio calculated, and the histology of the testis tissues observed under the microscope. RESULTS: The testicular indexes of the mice were decreased by radiation-induced damage, but restored to some extent after intragastric medication, especially in Groups E, F and G. The levels of FSH, LH and T were obviously improved by LBP. The T level and testis weight were increased by Icariin. The level of T/E2 was elevated in Groups E, F and G. The best results were achieved in Group F, which exhibited almost complete recovery from reproductive endocrine disorder and spermatogenic damage. CONCLUSION: The Chinese medicinal monomer is effective for 60Co-gamma-induced spermatogenic disturbance in mice, and the compound suspension of resveratrol + LBP + icariin produces the best result.

[Shengjing granule: an effective Chinese medicine for spermatogenic disturbance in mice].

OBJECTIVE: To observe the effect of the Chinese medicine Shengjing Granule on spermatogenic disturbance in mice. METHODS: Forty-six male Kunming mice were randomly divided into a normal (n = 10), a model (n = 12), a control (n = 12) and a Shengjing group (n = 12), and models of spermatogenic disturbance were established by intraperitoneal injection of cyclophosphamide in the latter three. Then the first two groups received intragastric administration of physiological saline and the second two that of clomiphene (21.6 mg/kg x d) and Shengjing Granule (16 g/kg x d), respectively, all for 15 days. On the following day, the testis weight was measured, the levels of the follicle stimulating hormone (FSH), the luteinizing hormone (LH) and testosterone (T) determined by radioimmunoassay. Histological observations were made of the testis tissues under the microscope. RESULTS: The testis index and T level were (3.958 +/- 0.342) g/kg and (7.046 +/- 0.291) nmo/L, obviously increased, while the levels of FSH and LH were (2.947 +/- 0.587) mIU/ml and (3.254 +/- 0.492) mIU/ml, significantly decreased, in the Shengjing group, as compared with (3.525 +/- 0.462) g/kg, (6.231 +/- 0.317) nmol/L, (5.428 +/- 0.719) mIU/ml and (5.155 +/- 0.460) mIU/ml in the model group (P < 0.05). The number of spermatogenic cells on the seminiferous tubules and that of sperm in the lumina of the tubules were markedly increased in the Shenginjg group, compared with the models. CoCONCLUSIONShenginjg Granule is effective for spermatogenic disturbance in mice.

[Shengjing Granule for varicocele in rats].

OBJECTIVE: To study the influence and therapeutic effect of the Chinese herbal drug Shengjing Granule on varicocele in rats. METHODS: A total of 80 male Sprague-Dawley rats were equally randomized into a sham operation group and 3 varicocele model groups, and the latter 3 again subdivided into a model, a Shengjing and a Clomifene group. Fifteen days after the modeling, the Shengjing and the Clomifene groups were intragastrically given Shengling Granule and Clomifene at the dose of 4 g/(kg x d) and 20 mg/(kg x d), respectively, while the model and sham operation groups were on normal diet. Thirty days later, the effects of Shengjing Granule were assessed by determining such serum sexual hormones as FSH, LH and T and observing the morphological changes of the testes of different groups of rats under the light microscope. RESULTS: The testis constitution was better and the levels of FSH and LH were significantly lower in the Shengjing group than in the model and Clomifene groups (P<0.05) but markedly higher in the Clomifene group than in the other three. The T level showed no obvious difference among the Shengjing, Clomifene and sham operation groups but was significantly higher in the three groups than in the model group (P<0.05). CONCLUSION: Shengjing Granule can not only protect the testis from but also repair varicocele-induced injury, probably with a better efficacy than Clomifene.