OBJECTIVE To identify core genes associated with the treatment of coronary heart disease （CHD） with Tongmai yangxin pills， and predict their potential immunological and metabolic mechanisms. METHODS Mendelian randomization （MR） analysis was conducted using protein quantitative trait loci （pQTL） data from the UK Biobank and Icelandic，and data from genome- wide association study to screen core genes related to Tongmai yangxin pills in the treatment of CHD. Gene expression changes were further validated using transcriptomic sequencing data. Mediation analyses of immune cells and plasma metabolites were subsequently performed to explore the downstream regulatory networks of these core genes. RESULTS A total of 62 positive pQTL genes showed significant causal associations with CHD. MR analysis combined with transcriptomic sequencing validation identified three core genes FAM3D，OXT， and ENPP5-associated with Tongmai yangxin pills in the treatment of CHD. The transcriptomic sequencing results showed that after treatment with Tongmai yangxin pills， the expression levels of FAM3D and OXT were significantly reduced （P＜0.01）， while the expression level of ENPP5 was significantly increased （P＜0.05）. Mediation analyses between immune cells and plasma metabolites indicated that these genes may positively or negatively regulate CHD through immune pathways involving regulatory T cells and myeloid dendritic cells expressing CD11c and CD62L， as well as through metabolic pathways related to lipid and fatty acid metabolism， cholesterol metabolism， and bile acid metabolism. CONCLUSIONS This study identified FAM3D，OXT， and ENPP5 as core genes associated with the treatment of CHD by Tongmai yangxin pills， which may exert therapeutic effects via modulation of immune cells and plasma metabolic pathways involving fatty acids and bile acids.

Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.

Malignant tumors in children are one of the most important diseases that threaten the health and quality of life of children and are the second most common cause of death in children.With the continuous improvement and progress of treatment technology, the long-term survival rate of children with tumor has been significantly improved, but both the disease itself and the treatment can impair the immune function of children, which makes them vulnerable to various infectious diseases and secondary serious complications, and even become a source of infection, endangering the health of others. Vaccination is the most cost-effective measure to prevent infectious diseases. For children with normal immune functions, the benefits of vaccination usually outweigh the disadvantages. However, there is a lack of detailed data on the vaccination situation, efficacy and safety of vaccine use for such immunocompromised tumor survivors, and there are no authoritative and uniform vaccination recommendations. This article reviewed and summarized the literature and consensus of some domestic and foreign scholars on current status of post-treatment vaccination status, efficacy and safety of vaccination for children with tumors after treatment, with the aim of providing a reference for the practice in this field in China.

Purpose To investigate the diagnostic value of postsystolic shortening in ischemia with non-obstructive coronary arteries(INOCA).Materials and Methods A total of 85 INOCA patients admitted to People's Hospital of Liaoning Province from May 2020 to December 2022 were selected and divided into two groups according to the ratio of distal diastolic average blood velocity of left anterior descending branch before and after treatment obtained by thymosidine load echocardiography(coronary flow velocity reserve,CFVR):CFVR<2.0 was in the coronary microvascular dysfunction(CMD)group(n=40),and CFVR≥2.0 was in the control group(n=45).Conventional echocardiographic parameters of all enrolled subjects were measured:left ventricular end-diastolic diameter index(LVEDDI),left ventricular end-diastolic volume index(LVEDVI),left ventricular end-systolic volume index(LVESVI),left ventricular ejection fraction(LVEF),early and late mitral valve diastolic blood flow velocity(E,A),E/A,average velocity of mitral valve annulus and interventricular septum in early diastolic(e')and E/e'on the wall and septal side were measured.The global longitudinal strain(GLS)and the post systolic index(PSI)of the left ventricle were measured by two-dimensional speckle tracking automated functional imaging.The differences of echocardiographic parameters,GLS and PSI between CMD group and control group were observed.The relationship between CFVR and PSI in CMD group was analyzed.Results There were no significant differences in LVEDDI,LVEDVI,LVESVI,LVEF,E,A,E/A,e',E/e'and GLS between control group and CMD group(t=-0.577-1.472,P>0.05).There was a statistically significant difference in PSI increase between CMD group and control group(t=-5.370,P<0.05).There was a good correlation between CFVR and PSI in CMD group(r=-0.486,P<0.05).The receiver operator characteristic curve showed that the area under the curve predicted by PSI for CMD was 0.786,the sensitivity was 68.0%,and the specificity was 77.8%.Conclusion PSI has good application value in evaluating left ventricular systolic function in INOCA patients,and can detect left ventricular systolic function injury in such patients at an early stage.

L-theanine has been shown to have a therapeutic effect on depression.However,whether L-theanine has an excellent preventive effect on depression in children and adolescents and what its mechanism is have not been well explained.Given the complexity of the pathogenesis of depression,this study investigated the preventive effect and mechanism of L-theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies.Behavioral tests,hippocampal tissue sections,and serum and hippocampal biochemical indexes were studied,and the results confirmed the preventive effect of L-theanine.Untargeted reversed-phase liquid chromatography-quadrupole-time-of-flight mass spec-trometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spec-trometry were developed to analyze the metabolism changes in the serum and hippocampus to screen for potential biomarkers related to L-theanine treatment.The results suggested that 28 abnormal me-tabolites in the serum and hippocampus that were considered as potential biomarkers returned to near-normal levels after L-theanine administration.These biomarkers were involved in various metabolic pathways,mainly including amino acid metabolism and lipid metabolism.The levels of amino acids and neurotransmitters in the phenylalanine,tryptophan,and glutamic acid pathways were significantly reduced after L-theanine administration compared with chronic unpredictable mild stress-induced rats.In summary,L-theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body,such as amino acids,lipids,and inflammation.This research systematically analyzed the mechanism of L-theanine in preventing depression and laid the foundation for applying L-theanine to prevent depression in children and adolescents.

OBJECTIVE: To explore the coagulation deficit and genetic basis for a Chinese pedigree affected with Congenital dysfibrinogenemia (CD). METHODS: Peripheral venous blood samples of the proband and her family members (including 4 individuals from three generations) were subjected to routine blood test and assays of liver and kidney functions and viral hepatitis to exclude related diseases. Clauss method and DFg-PT method were used to determine the fibrinogen activity (Fg:C), and an immunoturbidimetric assay was used to determine the level of fibrinogen antigen (Fg:Ag). All of the exons (22 in total) and their flanking sequences of the FGA, FGB and FGG genes were amplified by PCR and directly sequenced. Variants in the coding regions of the three genes and transcriptional splicing sites were screened by using Mutation Surveyor^TM software. RESULTS: The Clauss method showed that Fg:C was significantly reduced in the proband and her father, whilst her mother and son were normal. With the DFg-PT method, the proband, her parents and son were all within the normal range. The Fg:C/Fg:Ag ratio of the proband and her father was lower than 0.7, whilst her mother and son were above 0.7. No significant change in the prothrombin time, activated partial thromboplastin clotting time and thrombin time was noted. Two genetic variants were detected, which included a homozygous missense variant in the FGA gene [c.991A>G (p.Thr331Ala)], which was predicted to be benign, and a heterozygous missense variant of the γ chain of the FGG gene [c.1211C>G (p.Ser404Phe)], which is located in a conserved region and unreported in the CLINVAR/HGMD/EXAC/1000G databases and literature. CONCLUSION This pedigree has conformed to the autosomal dominant inheritance of CD. The c.1211C>T (p.Ser404Phe) missense variant of the γ chain of the FGG gene probably underlay the pathogenesis of CD in this pedigree. The variant was unreported previously and named as "Fibrinogen Harbin II Ser404Phe".
Female ; Humans ; Afibrinogenemia/congenital* ; East Asian People ; Fibrinogen/genetics* ; Mothers ; Mutation ; Pedigree

OBJECTIVE: To investigate the correlation of procalcitonin (PCT), interleukin-6 (IL-6) and antithrombin III (AT III) with the severity of sepsis, and to compare the predictive value of the above indicators alone or in combination. METHODS: A retrospective cohort study was conducted. Eighty-five patients with sepsis admitted to the department of intensive care medicine of Shandong Provincial Hospital Affiliated to Shandong First Medical University from April 2021 to September 2022 were enrolled. General information, sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation II (APACHE II) score within 24 hours of admission, inflammatory indicators [PCT, IL-6, serum amyloid A (SAA), neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP)] and coagulation indicators (D-dimer and AT III) levels at admission, and 28-day prognosis were collected. The differences of the above indicators were compared among patients with different prognosis at 28 days and different severity of sepsis. The correlation between PCT, IL-6, AT III and the severity of sepsis was analyzed by Spearman rank correlation method. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCT, IL-6 and AT III alone or in combination on the 28-day death of patients with sepsis. RESULTS: Eighty-five patients were enrolled finally, 67 cases survived and 18 cases died at 28 days. The mortality was 21.2%. There were no statistical significant differences in gender, age and other general data between the two groups. The patients in the death group were more serious than those in the survival group, and PCT, IL-6, and CRP levels were significantly higher than those in the survival group [PCT (μg/L): 4.34 (1.99, 14.42) vs. 1.17 (0.31, 3.94), IL-6 (ng/L): 332.40 (50.08, 590.18) vs. 61.95 (31.64, 194.20), CRP (mg/L): 149.28 (75.34, 218.60) vs. 83.23 (48.22, 174.96), all P < 0.05], and AT III activity was significantly lower than that in the survival group [(53.67±28.57)% vs. (80.96±24.18)%, P < 0.01]. However, there were no significant differences in D-dimer, NLR and SAA between the two groups. Among the 85 patients, 36 had sepsis with single organ dysfunction, 29 had sepsis with multiple organ dysfunction, and 20 had septic shock with multiple organ dysfunction. With the increase of the severity of sepsis, PCT and IL-6 levels gradually increased [PCT (μg/L): 0.36 (0.19, 1.10), 3.00 (1.22, 9.94), 4.34 (2.18, 8.86); IL-6 (ng/L): 43.99 (20.73, 111.13), 100.00 (45.37, 273.00), 332.40 (124.4, 693.65)], and the activity of AT III decreased gradually [(89.81±21.42)%, (71.97±24.88)%, and (53.50±25.41)%], all with statistically significant differences (all P < 0.01). Spearman rank correlation analysis showed that PCT and IL-6 levels in sepsis patients were significantly positively correlated with the severity of the disease (r values were 0.562 and 0.517, respectively, both P < 0.01), and AT III activity was significantly negatively correlated with the severity of the disease (r = -0.523, P < 0.01). ROC curve analysis showed that PCT, IL-6, and AT III alone or in combination had some predictive value for the death of sepsis patients at 28 days. The area under the ROC curve (AUC) of the above three indicators in combination was higher than that of the individual tests (0.818 vs. 0.722, 0.725, and 0.770), with a sensitivity of 83.3% and a specificity of 73.1%. CONCLUSIONS PCT, IL-6, and AT III were significantly correlated with the severity of sepsis patients. The combined assay of the above three indicators can effectively improve the prediction of the prognosis of sepsis patients.
Humans ; Procalcitonin ; Interleukin-6 ; Antithrombin III ; Retrospective Studies ; Multiple Organ Failure ; ROC Curve ; Sepsis/diagnosis* ; Prognosis ; C-Reactive Protein/analysis* ; Anticoagulants

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

ObjectiveTo study the effect of organophosphate-solubilizing bacteria and compound bacteria on the photosynthesis and physiological and biochemical characteristics of leaves of Paris polyphylla var. yunnanensis， and to provide a reference for selecting suitable bacterial fertilizers in artificial cultivation of this medicinal species. MethodPot experiment was carried out indoor and the following groups were designed： control （CK）， inoculation with Bacillus mycoides （S1）， inoculation with B. wiedmannii （S2）， inoculation with B. proteolyticus （S3）， inoculation with B. mycoides and B. wiedmannii （S4）， inoculation with B. mycoides and B. proteolyticus （S5）， inoculation with B. wiedmannii and B. proteolyticus （S6）， and inoculation with B. mycoides， B. wiedmannii and B. proteolyticus （S7）. Then， the growth and development， photosynthesis， and various physiological and biochemical indexes of the leaves of this species were observed. ResultCompared with CK， the treatment groups showed decrease in content of malondialdehyde in the leaves （P<0.05）， particularly S7 （content was only about 1/3 that of the CK）. The leaf area， photosynthetic parameters， photosynthetic pigment content， soluble sugar content， soluble protein content， and activity of superoxide dismutase （SOD）， peroxidase （POD）， and catalase （CAT） in leaves of the treatment groups were all improved. Among them， the leaf area， soluble sugar content， and soluble protein content were the highest in S7， which were 2.8， 2.1， and 2.2 times that of the CK， respectively. SOD activity peaked in S6 （2.9 times higher than that in the CK） and the highest activity of POD and CAT was detected in S5 （1.5 times and 2.1 times， respectively higher than that in the CK）. ConclusionInoculation with different organophosphate-solubilizing bacteria or compound bacteria can promote the growth and development of P. polyphylla var. yunnanensis and improve its resistance to stresses. The combination of B. mycoides and B. proteolyticus and the combination of the three achieved the have the best effect. This study provides a reference for the selection of bacterial fertilizers for artificial cultivation of P. polyphylla var. yunnanensis.

Objective:To compare the clinical efficacy and safety of continuous dosing or alternate-day dosing of apatinib combined with SOX regimen as first-line treatment for patients with advanced gastric cancer.Methods:A total of 52 patients with human epidermal growth factor receptor 2 (HER2) negative and inoperable locally advanced or advanced gastric cancer who were pathologically diagnosed from January 2018 to January 2021 in the Second Affiliated Hospital of Shandong First Medical University were collected. The patients were divided into continuous dosing group and alternate-day dosing group by random number table method. The continuous dosing group received apatinib (250 mg, once a day) combined with SOX regimen (S-1+oxaliplatin); the alternate-day dosing group received apatinib (250 mg, once every other day) combined with SOX regimen. Twenty-one days were a cycle, and the efficacy was evaluated after 2 cycles. After 4-6 cycles, patients with stable disease received apatinib and S-1 for maintenance therapy. The therapeutic effects and adverse reactions of the two groups were compared.Results:The curative effect could be evaluated in 51 patients, including 26 in the continuous dosing group and 25 in the alternate-day dosing group. The disease control rates in the continuous dosing group and the alternate-day dosing group were 84.6% (22/26) and 76.0% (19/25) ( χ2 = 0.60, P = 0.499), and the median progression-free survival time was 7.50 months (95% CI 6.17-8.83 months) and 8.30 months (95% CI 6.99-9.61 months) ( χ2 = 0.71, P = 0.401), and the median overall survival time was 15.50 months (95% CI 11.30-19.69 months) and 15.60 months (95% CI 13.63-17.57 months) ( χ2 = 1.82, P = 0.177). The main adverse reactions in the two groups were leukopenia, thrombocytopenia, hypertension, nausea, vomiting, fatigue, hand-foot syndrome, proteinuria, liver and kidney damage. The incidence rates of ≥grade 3 adverse reactions in the continuous dosing group and the alternate-day dosing group were 42.3% (11/26) and 12.0% (3/25), and the difference was statistically significant ( χ2 = 4.46, P = 0.035). Conclusions:The efficacy of continuous dosing or alternate-day dosing of apatinib combined with SOX regimen as first-line treatment for advanced gastric cancer is similar, but the incidence of ≥grade 3 adverse reactions in alternate-day dosing group is lower, which improves the compliance and tolerance of patients.