Changes in serum indoleamine 2, 3-dioxygenase and kynurenic acid levels in preterm infants with bronchopulmonary dysplasia / 中华围产医学杂志

Objective:To explore the changes in serum indoleamine 2, 3-dioxygenase (IDO) and kynurenic acid (KYNA) levels in preterm infants diagnosed with bronchopulmonary dysplasia (BPD).Methods:A nested case-control study was conducted. The inclusion criteria covered premature infants with less than 32 weeks of gestational age within 24 h post-birth, from December 1, 2021, to December 31, 2022, at Children's Hospital of Soochow University. Those diagnosed with BPD were allocated to the BPD group ( n=35). Non-BPD preterm infants matching the BPD cases in terms of gestational age (within one week difference) and birth weight (within a 150 g difference) were selected in a 1∶1 ratio for the control group ( n=35). Serum levels of IDO and KYNA were measured on days 1, 7, 14, and 28 postnatally. Differences in serum IDO and KYNA levels were analyzed between the BPD and control groups and among infants with mild BPD versus moderate-to-severe BPD. The association between serum IDO and KYNA levels with the severity of BPD was also assessed. Statistical analysis was conducted using independent samples t-tests and Spearman's correlation analysis. Results:Elevated levels of serum IDO on days 7, 14, and 28 postnatally [(60.68±9.37) vs. (50.66±10.46), (57.81±11.07) vs. (44.45±8.20), and (50.62±10.77) vs. (41.31±7.74) pg/ml; t=4.21, 5.73, and 4.15, respectively] as well as increased serum KYNA levels on days 14 and 28 [(439.31±41.22) vs. (368.99±68.79), (376.97±45.74) vs. (325.50±60.07) μmol/L; t=5.18 and 4.03, respectively] were observed in the BPD group compared to the control group, with all differences being statistically significant (all P<0.05). Furthermore, positive correlations were observed between serum IDO levels and BPD severity on the 7th, 14th, and 28th days ( r=0.546, 0.495, and 0.502, all P<0.05), as well as between serum KYNA levels and BPD severity on the 14th and 28th days ( r=0.536 and 0.458, both P<0.05). Conclusion:Elevated serum levels of IDO and KYNA in infants with BPD suggest these metabolites may play a role in the pathogenesis and progression of BPD.

Treatment of Paroxysmal Atrial Fibrillation by Deficiency-Excess Pattern Identification Based on “Palpitations Caused by Wind Pathogen” / 中医杂志

Paroxysmal atrial fibrillation can be attributed to the category of xinji （palpitations） and zhangchong （severe palpitations） in traditional Chinese medicine， and its onset has the characteristics of urgency， change， and movement， which is similar to the characteristics of diseases induced by wind pathogen. It is believed that the internal movement of wind pathogen runs through the whole course of this disease， and palpitations due to wind as the direct pathogenesis. Palpitations caused by wind pathogen showed different characteristics of deficiency and excess pattern. In the acute exacerbation period， excess wind is the main cause of disease. For excessive heat generating wind， the treatment is to clear the liver and extinguish wind by self-modified Lingxia Qinggan Decoction （羚夏清肝汤）； for blood stasis generating wind， the treatment is to remove blood stasis and stop wind by self-modified Yandan Limai Decoction （延丹理脉汤）； for phlegm-heat accumulation with wind， the treatment is to dissolve phlegm and eliminate wind by self-modified Lianlou Danxing Decoction （连蒌胆星汤）. In the prolonged recovery period， deficiency wind is more common. For stirring of wind due to yin deficiency， the treatment is to nourish yin and extinguish wind by self-modified Zaoshao Zhenzhu Deoction （枣芍珍珠汤）； for spleen deficiency generating wind， the treatment is to strengthen spleen and nourish wind by self-modified Shenying Dingji Deoction （参英定悸汤）. Clinical prescriptions closely follow the characteristics of wind， weigh the changes of deficiency and excess， tailor with the patterns， and regulate qi and blood of the zang-fu organs， in order to extinguish wind and arrest convulsion.

Chloroplast genomic characterization and phylogenetic analysis of Castanopsis hystrix / 生物工程学报

The structure and size of the chloroplast genome of Castanopsis hystrix was determined by Illumina HiSeq 2500 sequencing platform to understand the difference between C. hystrix and the chloroplast genome of the same genus, and the evolutionary position of C. hystrix in the genus, so as to facilitate species identification, genetic diversity analysis and resource conservation of the genus. Bioinformatics analysis was used to perform sequence assembly, annotation and characteristic analysis. R, Python, MISA, CodonW and MEGA 6 bioinformatics software were used to analyze the genome structure and number, codon bias, sequence repeats, simple sequence repeat (SSR) loci and phylogeny. The genome size of C. hystrix chloroplast was 153 754 bp, showing tetrad structure. A total of 130 genes were identified, including 85 coding genes, 37 tRNA genes and 8 rRNA genes. According to codon bias analysis, the average number of effective codons was 55.5, indicating that the codons were highly random and low in bias. Forty-five repeats and 111 SSR loci were detected by SSR and long repeat fragment analysis. Compared with the related species, chloroplast genome sequences were highly conserved, especially the protein coding sequences. Phylogenetic analysis showed that C. hystrix is closely related to the Hainanese cone. In summary, we obtained the basic information and phylogenetic position of the chloroplast genome of red cone, which will provide a preliminary basis for species identification, genetic diversity of natural populations and functional genomics research of C. hystrix.

Progress of T lymphocytes in the pathogenesis of bronchopulmonary dysplasia in premature infants / 国际儿科学杂志

Bronchopulmonary dysplasia(BPD)is a severe complication in premature infants, and the pathogenesis remains complex, potentially involving pulmonary inflammatory injury and faulty reparative response.T-cell immaturity in preterm neonates and the upregulation of related harmful regulatory genes, as well as the imbalance of T-cell homeostasis, have been reported to contribute significantly to the development of inflammatory diseases.Growing evidence suggests that alterations in the levels and functions of T cell subsets may participate in the development of BPD, serving as a new avenue for BPD prevention and treatment.Herein, we summarize recent advancements in understanding the role of T lymphocytes in the pathogenesis of BPD.

Analysis of clinical features of neonatal and infantile pertussis / 国际儿科学杂志

Objective:To analyse the clinical features and prognosis of pertussis in neonates and infants.Methods:The clinical data of neonates and infants with pertussis hospitalized in Children′s Hospital of Soochow University from September 2021 to September 2022 were retrospectively analyzed and grouped in terms of age, the severity of the disease, and whether a mixed infection, respectively.Results:A total of 40 infants with pertussis were analyzed.All cases showed improvement and were discharged after receiving active anti-infective treatment.In the neonatal group, higher rates of apnea and hyponatremia were observed compared to the non-neonatal group(all P<0.05).Additionally, peripheral blood leukocyte counts[20.9(15.0, 28.7)×10 9/L vs.16.6(11.3, 21.2)×10 9/L], neutrophil counts[4.6(3.7, 7.9)×10 9/L vs.3.2(2.1, 5.3)×10 9/L], γ-glutamyltransferase levels[78.0( 50.2, 109.4)U/L vs.22.5(15.1, 38.9)U/L], duration of hospitalization[21.5(16.8, 25.0)d vs.11.5(9.0, 19.8)d], and duration of oxygen use[7.0(0, 21.0)d vs.0(0, 2.3)d]were higher in the neonatal group than in the non-neonatal group(all P<0.05).However, the IgA level[0.02(0.02, 0.04)g/L vs.0.05(0.03, 0.09)g/L]was significantly lower in the neonatal group than in the non-neonatal group( P<0.05).In the severe group, the proportion of onset age of less than 3 months, fever, wheezing, shortness of breath, cyanosis after rough cough, apnea, decreased heart rate, wet rales on lung auscultation, respiratory failure, cardiac insufficiency, hyponatremia, CRP>8 mg/L, spotty/patchy shadows in the lungs, as well as the use of gammaglobulin, cardioactive drug and invasive ventilation, were higher than those in the non-severe group(all P<0.05).Furthermore, peripheral blood leukocyte counts[21.0(15.4, 37.4)×10 9/L vs.17.5(11.8, 21.2)×10 9/L], neutrophil counts[5.6(4.0, 10.7)×10 9/L vs.3.2(2.3, 4.6)×10 9/L], neutrophil to lymphocyte ratio[(0.6±0.4) vs.( 0.3±0.2)], systemic immune-inflammation index[237.5(109.5, 424.9) vs.135.9(75.4, 190.5)], γ-glutamyltransferase level[53.2(31.6, 87.4)U/L vs.29.5(15.2, 65.0)U/L], duration of oxygen use[18.0(12.8, 22.5)d vs.0(0, 0)d], and duration of hospitalization[24.5(21.8, 31.2)d vs.12.0(9.0, 16.8)d]were higher in the severe group than those in the non-severe group(all P<0.05).However, the IgA level[0.03(0.02, 0.04)g/L vs.0.05(0.03, 0.09)g/L]was significantly lower in the severe group than in the non-severe group( P<0.05).The mixed infection group had a longer duration of hospitalization and a higher proportion of fever than the single infection group(all P<0.05). Conclusion:Early detection of infantile pertussis can be challenging.Neonates with pertussis tend to experience severe symptoms, such as apnea, hyponatremia, elevated white blood cell count, and longer duration of oxygen use.Symptoms such as fever, wheezing, shortness of breath, decreased heart rate, wet lung rales, and spotty/patchy shadows in the lungs, as well as early elevated CRP, neutrophil to lymphocyte ratio, systemic immune-inflammation index, and decreased IgA levels are indicators of disease exacerbation.In mixed infections group, there is a higher proportion of fever.

Progress in therapeutic potential of human breast milk-derived exosomes in neonate necrotizing enterocolitis / 中华围产医学杂志

Neonatal necrotizing enterocolitis (NEC) is one of the leading causes of neonatal death and no effective therapeutic drugs are currently available. Breastfeeding is a safe and effective preventive measure for NEC. Human breast milk-derived exosomes (HM-exos), which are membranous vesicles in breast milk, play an important role in maintaining the integrity of the intestinal barrier and promoting the repair of intestinal epithelial cells (IECs) damage through protecting IECs from oxidative stress, improving the proliferation and migration of IECs, maintaining the tight connection between IECs, inhibiting inflammatory response and regulating immune response.

A Study of Plasma Exosome Protein Spectrum in Coronary Heart Disease Patients with Phlegm Turbidity Syndrome and Healthy People / 世界科学技术-中医药现代化

Objective To explore the specific plasma exosomal protein expression in Coronary Heart Disease(CHD)with phlegm-turbidity syndrome(PTS),so as to provide biological reference for the diagnosis of CHD with PTS.Methods A total of 20 CHD patients with PTS and 20 healthy subjects at the same period were included.Plasma exosomes were extracted from all subjects using the qEV size exclusion method.First,10 CHD cases with PTS and 10 healthy subjects were randomly selected,and differentially expressed proteins between the two groups were screened using label free non-targeted protein quantification analysis.Then,MRM targeting protein labeling technique was applied to verify the differentially expressed proteins in the remaining subjects.Results Compared with healthy controls,214 differentially expressed plasma exosomal proteins(61 up-regulated and 153 down-regulated)were found in CHD patients with PTS,mainly related to cholesterol metabolism,complement and coagulation cascade,and immune effects.ANXA6,C4BPB,F8,CFB,APOE,C9,and CLU proteins were further validated by MRM targeting protein.Conclusion CHD patients with PTS had differences in plasma exosomal protein expression from healthy controls,and the differential proteins are mainly related to cholesterol metabolism,complement,and the coagulation cascade.

Progress on the application of metabolomics in early diagnosis of neonatal necrotizing enterocolitis / 国际儿科学杂志

Neonatal necrotizing enterocolitis(NEC)is a common and dangerous gastrointestinal disease in the neonatal period, with high morbidity and mortality, and the quality of life of some surviving children with NEC is seriously affected.In recent years, the rapid development of metabolomics technology, which provides dynamic qualitative and quantitative analysis of the intermediate and end products involved in biochemical reactions in organisms, explains disease occurrence and development from a systemic perspective, and has broad application prospects in the study of early diagnosis of NEC.The paper reviews the recent research results of metabolomics in the early diagnosis of NEC, aiming to provide a reference basis for the application of metabolomics technology in the early diagnosis of NEC.

Application of point-of-care ultrasound in NICU / 国际儿科学杂志

Point-of-care ultrasound(POCUS)was dominated by emergency or intensive medical doctors.POCUS was a technology which was used to explain the pathophysiological changes, diagnosis and treatments.POCUS was widely used in the evaluation of hemodynamics, lung diseases and the airway managements.In pediatric field, especially the critically newborn treatment, POCUS has brightly prospects.The application progresses of POCUS in neonatal intensive care unit were reviewed in this article.

Current research on pathogenesis and early diagnosis of necrotizing enterocolitis / 国际儿科学杂志

Neonatal necrotizing enterocolitis(NEC)is an inflammatory intestinal disorder that seriously threatens the life of neonates(especially premature babies). The pathogenesis of NEC remains uncertain.The main factors thought to be connected with the pathogenesis of NEC are: intestinal immaturity, enteral feeding, the intestinal microecological imbalance, inflammation, ischaemia-reperfusion injury and genetic predisposition.The clinical manifestations of NEC are diversified and early symptoms are concealed.It is easy to be misdiagnosed or missed, delayed treatment.Imaging techniques such as abdominal X-ray or ultrasound, intestinal microbiome and its metabolites determination, biomarkers and other methods contribute to early diagnosis.This article reviews the advances in the pathogenesis and early diagnosis of NEC to guide clinical prevention and treatment.

Determination of the Potential Genotoxic Impurities in Oxiracetam Raw Material by GC-MS / 中国药师

Objective:To establish a method for the determination of the potential genotoxic impurities [ methyl chloroacetate and ( R, S) 4-ethyl chloro-3-hydroxybutyrate ] in oxiracetam raw material .Methods:GC-MS was conducted , and the potential genotoxic impurities were extracted by ethyl acetate .The column was a VF-1701 ms capillary column (30 m ×0.25 mm, 0.25 μm) with pro-grammed temperature and the inlet temperature was 220 ℃.The column flow was 1.0 ml· min-1 and the purge flow was 5.0 ml· min-1 .The split injection was used and the split ratio was 5:1 .The carrier gas was high purity helium and the detector was a mass spectrometer detector .The ion source temperature was 230℃and the interface temperature was 230 ℃.The delay time of solvent was 4 min and the ionization mode was electron impact .The scanning ( detection ) method was selective ion monitoring , the electron energy was 70 eV, and the injection volume was 1.0 μl.Results:The separation between the impurities met the requirements .The concen-tration linear range was 50-400 ng· ml-1 (r≥0.9995).The recoveries were 89.7％-96.3％ (RSD=2.3％, n=9) and 91.0％-105.3％(RSD=4.4％, n=9), respectively.Conclusion:The method is simple, accurate, sensitive and rapid, and can be used for the determination of two potential genotoxic impurities in oxiracetam raw material .

The application of prostate specific antigen in differential diagnosis of benign and malignant prostatic tumors / 国际检验医学杂志

Objective To investigate serum total prostate special antigen(tPSA),complexed prostate special antigen(cPSA)and cPSA/tPSA ratio(C/T) in the differential diagnosis of benign prostate hyperplasia(BPH)and prostate cancer(PCa).Methods A total of 184 serum samples from hospital outpatient and inpatient were collected from May 2009 to December 2015,and which were divided into three groups including other diseases 68 patients,benign prostate hyperplasia(BPH group)80 patients,prostate cancer (PCa group)36 patients.Chemiluminescence immunoassay was used to detect the concentration of tPSA and cPSA,and the C/T ratio were calculated in the study.Results The tPSA,ePSA levels and C/T ratio were significant different from patients with PCa,BPH and other diseases group(P＜0.01).Compared with BPH group(r=0.661),the tPSA and cPSA levels have a higher relativity in PCa group(cPSA=0.708 × tPSA-0.219,r=0.956).While when tPSA level ranges 4.0-10.0 ng/mL),no significant difference of tPSA,cPSA levels and C/T ratio were found in these 3 groups(P＞0.05).Conclusion Combined detection of serum tPSA,cPSA and C/T,making importance in the differential diagnosis of BPH and PCa.

PERK/eIF2a/CHOP signal pathway involved in the pathogenesis of necrotizing enterocolitis in neonatal rats / 中华实用儿科临床杂志

Objective By establishing multivariate necrotizing enterocolitis (NEC) model in newborn rats to study the expression of the related molecules protein kinase R-like ER kinase(PERK),pho-protein kinase R-like ER kinase(p-PERK),eukaryotic translation initiation factor 2 alpha(eIF2a),pho-eukaryotic translation initiation factor 2 alpha (p-eIF2a),CCAAT/enhancer-binding protein-homologous protein (CHOP) in the PERK/eIF2a/ CHOP signaling pathway to explore the pathogenesis of NEC,and in order to provide a theoretical basis for clinical pre-vention and treatment of NEC.Methods One hundred and fifty neonatal Sprague-Dawley (SD) rats were divided into 3 groups according to random number table.NEC group:fed with formula,experienced hypoxia and cold stress,and lipopolysaccharide(LPS) fed via orogastric gavage to induce NEC model.Salubrinal(SAL) group:estabhshing NEC model and intraperitoneal injection of SAL (1 mg/kg).Control group:the same amount of 9 g/L saline was injected intraperitoneally.Ten rats selected from each group randomly were decapitated at 0,12,24,48 and 72 h,respectively,and intestinal tissues were obtained,intestinal general situation and made pathology scores observed.Expressions of PERK,p-PERK,eIF2a,p-eIF2a,CHOP proteins were detected by Western blot technique and the expression levels of CHOP mRNA gene were detected by real-time polymerase chain reaction.Results The control group had no NEC.The incidence of NEC in NEC group was 90％ (9/10 cases).The incidence of NEC in SAL group was 40％ (4/10 cases).The p-PERK and p-eIF2a protein expressions in NEC and SAL groups were increased with the modeling time.The p-PERK and p-eIF2a protein expressions of NEC and SAL groups were up-regulated compared with the control group (p-PERK:1.528 ± 0.264,1.402 ± 0.233 vs.0.303 ± 0.036;p-eIF2a:0.969 ± 0.076,1.173 ± 0.066 vs.0.209 ±0.045;P ＜0.05).The p-eIF2a protein expressions of SAL group were higher than those of the NEC group (P ＜ 0.05).The CHOP protein and CHOP mRNA expressions in the NEC and the SAL groups were increased with the modeling time.The CHOP protein and CHOP mRNA expressions of NEC and SAL groups were up-regulated than those of the control group (CHOP protein:1.456 ± 0.223,0.929 ± 0.064 vs.0.165 ± 0.026;CHOP mRNA:0.343 ±0.035,0.198 ± 0.044 vs.0.017 ± 0.010;P ＜ 0.05).The CHOP protein and CHOP mRNA expressions of SAL group were lower than that in the NEC group (P ＜ O.05).Conclusions The PERK/eIF2a/CHOP signal pathway may participate in NEC,and salubrinal probably by inhibiting p-eIF2a dephosphorylation,and inhibiting CHOP gene and protein expression to work.

Mechanism of apoptosis induced by Mcl-1 inhibitor UMI-77 on gastric cancer MGC-803 cells / 安徽医科大学学报

Objective To investigate the mechanism of apoptosis induced by UMI-77 , a novel selective inhibitor of Mcl-1, in gastric cancer MGC-803 cells. Methods MGC-803 cells were treated with UMI-77 in different concen-trations for 24 h, apoptotic rates were determined by Annexin V/PI method using flow cytometry. Mitochondrial membrane potential was determined by JC-1 staining on a flow cytometer. The activation of Caspase-9, Caspase-3 and cleavage of PARP were measured by Western blot analysis. The protein level of Bcl-2, Bcl-XL and Mcl-1 was monitored by Western blot as well. Chemically synthesized Mcl-1 siRNA was transfected into MGC-803 cells using Lipofectamine 2000 Reagent. The efficacy of gene silencing was confirmed by Western blot analysis, and opoptotic rates before and after transfection was measured by flow cytometry using Annexin V/PI staining. Results UMI-77 was effective in induction of apoptosis in gastric cancer MGC-803 cells, apoptotic rates were increased in a dose-de-pendent manner. Mitochondrial membrane potential was collapsed after UMI-77 treatment. Activation of Caspase-9, Caspase-3 and cleavage of PARP occurred at 24 h (P<0. 05). The expression level of Bcl-2 and Bcl-XL were not altered after exposure to UMI-77 , while Mcl-1 was down-regulated after 12 h ( P<0. 05 ) . Transfection with Mcl-1 siRNA successfully decreased the expression level of Mcl-1 in MGC-803 cells ( P<0. 05 ) and blocked apoptosis induced by UMI-77 ( P<0. 05 ) . Conclusion UMI-77 induces apoptosis through activation of the intrinsic path-way in gastric cancer MGC-803 cells, and knocking down Mcl-1 expression abrogates apoptosis by UMI-77.

Diagnostic value and clinical significance of 3D-CE-MRA in infantile superficial hemangioma / 实用放射学杂志

Objective To investigate the diagnostic value and clinical significance of the three-dimensional contrast-enhanced MR angiography (3D-CE-MRA)in the infantile superficial hemangioma.Methods Forty-four children with superficial hemangioma un-derwent conventional and dynamic contrast-enhanced MRI.MRI scanning was started at the time of inj ection,and four dynamic pha-ses of images were acquired continually.Maximum intensity proj ection (MIP)images were reconstructed to show the blood vessels of the lesions in multiple phases.Results Forty-nine infantile superficial hemangiomas were detected by MRI,including a single le-sion in 41 patients and multiple ones in 3.3D-CE-MRA showed 37 lesions in 32 patients,and other 12 lesions were not found in 12 patients.Conclusion The conventional and dynamic contrast-enhanced MRI can reflect the location,number and the range of the su-perficial hemangioma,and show the relationship between the lesion and the surrounding tissues.3D-CE-MRA directly shows the blood supply of the tumors.

Activation of caspase-4 was involved in TRAIL-induced apoptosis of gastric cancer cells / 中国药理学通报

Aim To investigate the potential involve-ment of caspase-4 in TRAIL ( tumor necrosis factor-re-lated apoptosis-inducing ligand )-induced apoptosis in gastric cancer cells. Methods The effect of treatment with TRAIL /z-LEVD-fmk alone or in combination for 24 h on the apoptotic rate of gastric cancer cells was detected by FCM ( flow cytometry) using propidium io-dide DNA staining. Chemically synthesized three siR-NAs targeting caspase-4 gene were transfected into gas-tric cancer cells by Lipofectamine 2000 Reagent. The efficacy of gene silencing was confirmed by Western blot analysis . The apoptotic rates of gastric cancer cells to TRAIL before and after transfection with caspase-4 siRNA were observed by FCM. The expression level of GRP78 (78-ku glucose-regulated protein) protein was examined by Western blot, the classic endoplasmic re-ticulum stress inducer tunicamycin ( TM) was used as a control. The expression levels of caspase-4 and caspase-3 after TRAIL treatment were also measured by Western blot. Results z-LEVD-fmk decreased TRAIL-induced apoptosis of gastric cancer cells signifi-cantly(P<0. 05). As compared with negative control, the expression level of caspase-4 protein was reduced after transfection, and the apoptotic rate was also de-creased ( P <0. 05 ) . While TM induced marked up-regulation of GRP78 , treatment with TRAIL resulted in, albeit to a lesser extent, increases in GRP78, in-dicative of induction of ER stress by TRAIL. Activa-tion of caspase-4 and caspase-3 occurred early after TRAIL treatment. Conclusion Activation of caspase-4 contributes to TRAIL-induced apoptosis and is asso-ciated with induction of ER stress by TRAIL in gastric cancer cells.

Anti-tumor Effect of Phellinus Linteus and Coriolus Versicolor Capsule on S180 sarcoma and H22 hepatoma in mice / 中国实验方剂学杂志

Objective: To observe the anti-tumor effect of Phellinus Linteus and Coriolus Versicolor Capsules (PLCVC) in S180 sarcoma and H22 hepatoma animal models in mice. Methods: The sarcoma S1180 and hepatoma H22 models were established in mice. After 12 days of treatment, the animals were killed, and the subcutaneous sarcoma were separated and weighted. The levels of vascular endothelial growth factor(VEGF), CD4 and CD8 of S180 tumor tissue were investigated by immunohistochemical method. KM mice were intraperitoneal injected with H22 hepatoma cells, and treated with different experimental drugs. The survival time was observed and recorded, and life-prolongation rate was calculated. Result: PLCVC could inhibit the growth of S180 and H22 tumor, and inhibit the expression of VEGF, improve the expression of CD4 and CD8. The survival time of the mice treated by PLCVC were significantly longer than the untreated group. Conclusion: PLCVC can inhibit the growth of tumour, the mechanism is partially related to inhibiting angiogenesis and improving the immunological function.