In order to investigate the feasibility of the extract from Cyclocarya paliurus as an additive in cigarettes,the volatile aromatic components were analyzed by gas chromatography-ion mobility spectrometry(GC-IMS),and C.paliurus extract was pyrolyzed to simulate cigarette smoking by TGA-GC/MS.The cracking products of C.paliurus were analyzed in a nitrogen environment,and the possible cracking mechanism of the products was reasonably speculated.The results showed that aldehydes,alcohols,and ketones were the primary volatile aroma components of the C.paliurus extract,comprising 62.28%of the total aroma components.The cracking products of C.paliurus extract varied greatly under different temperature conditions.A total of 79 compounds were identified at 200,360,and 440℃,among which 24 aromatic components were clearly identified as having significant effects on cigarette style,including aldehydes,ketones,alcohols,phenols,furans,benzene series,and other natural aromatic substances.Among them,phenols containing a high concentration are mainly formed by compounds containing the structure of guaiacol unit and eugenol unit by side chain cleavage,demethylation,demethoxylation,dehydration,etc.Furan and its derivatives are mainly formed by glycosides or glycoside compounds by breaking glucoside bonds and dehydration.

This article reported a case of neurodevelopmental disorder accompanied by spastic diplegia and visual impairment with the manifestation of small fetal head circumference. Prenatal ultrasonography performed at 33 +5 weeks of pregnancy revealed small fetal head circumference (-2.61SD) and oligohydramnios. Whole-exome sequencing identified a heterozygous frameshift variation of c.1623_1624insA (p.R542Tfs*30) in the CTNNB1 gene (NM_001904.4) of the fetus. No phenotypic abnormalities or corresponding gene variations were detected in the parents, suggesting it was a de novo variation. Based on the clinical manifestations, the fetus was diagnosed with a neurodevelopmental disorder accompanied by spastic diplegia and visual defects. Following genetic counseling, the pregnant woman chose to terminate the pregnancy.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

Objective:To upgrade the wisdom of traditional wards through the internet of things platform to achieve intelligent and refined management of wards, and to evaluate the effect of the upgrade.Methods:In June 2020, the convenience sampling method was used to selecte two wards of the cardiology department of Shandong First Medical University as the pilot units of the affiliated provincial Hospital to implement the intelligent ward management mode. Based on the principle of easy transformation, easy construction and easy maintenance, on the basis of realizing the full coverage of the internet of things, the hardware and software system were connected to complete the intelligent upgrade of the traditional ward, and the structured observation and semi-structured interview methods were adopted to evaluate the upgraded work efficiency and the use experience of patients.Results:The time spent on vital sign collection and recording, nursing risk assessment and time spent, and signage production and hanging were (4.24 ± 0.87), (4.07 ± 0.86) and 0 min respectively, which were effectively reduced than those before the upgrade (6.50 ± 2.95), (4.73 ± 1.62) and (1.13 ± 0.43) min, with statistically significant differences ( t=8.04, 3.99, 28.96, all P<0.01). The results of semi-structured interviews showed that patients perceived the smart ward as intelligent, saving manpower and waiting time; simple to operate, improving the experience of healthcare workers and patients in using it; and untimely system updates. Conclusions:The wisdom upgrade of traditional wards can help refine patient management, improve work efficiency, and improve the experience of health care workers and patients in using them, which will be continuously improved in future development and can provide practical paths for reference for the wisdom upgrade of similar wards.

Objective:To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells.Methods:Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. Results:Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2 -ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2 -ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2 -ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2 -ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2 -ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2 -ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2 -ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2 -ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2 -ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2 -ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2 -ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2 -ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. Conclusions:The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. AKT may be involved in the effect of LPS on the inhibition of O-GlcNAc modification.

Objective:To understand the epidemiological and clinical characteristics of patients with tsutsugamushi disease in Zaozhuang City, Shandong Province, and to provide a basis for formulating effective diagnosis and treatment plan of tsutsugamushi disease. Methods:Retrospective analysis was carried out to collect clinical data of 38 patients with tsutsugamushi disease admitted to Zaozhuang Municipal Hospital of Shandong Province from 2018 to 2020. The epidemiological characteristics, clinical manifestations, laboratory examination results and drug treatment of patients with tsutsugamushi disease were analyzed. Results:Among the 38 patients with tsutsugamushi disease, 15 were males and 23 were females, aged (58.58 ± 14.47) years old; the occupation distribution was mainly farmers, accounting for 92.11% (35/38); the onset time was concentrated in October and November, accounting for 100.00% (38/38); the regional distribution was mainly in Yicheng District, accounting for 34.21% (13/38); 38 patients had a history of grassland/forest contact. All patients had fever, and other main symptoms were eschar (97.37%, 37/38), headache (68.42%, 26/38), fatigue (42.11%, 16/38), and whole body aches (36.84%, 14/38), etc. The results of laboratory examination mainly showed that C-reactive protein increased (89.47%, 34/38), procalcitonin increased (81.58%, 31/38), abnormal liver function (78.95%, 30/38), D-dimer increased (71.05%, 27/38), eosinophils decreased (60.53%, 23/38), and erythrocyte sedimentation rate increased (57.89%, 22/38). All 38 patients were cured after treated with doxycycline or azithromycin. Conclusions:The high incidence time of tsutsugamushi disease in Zaozhuang City is autumn. The clinical symptoms are mainly fever, eschar and headache. Doxycycline and azithromycin are the first choices for treatment of the disease.

Objective:To analyze the relationship between renin-angiotensin-aldosterone system (RAAS) gene polymorphisms and susceptibility to essential hypertension (EH) in military secret service personnel.Methods:In October 2019, military secret service personnel (162 people) who were recuperating in a sanatorium from January to December 2017 were selected as the research subjects, all of whom were Han and male. The patients (79 people) who were diagnosed with EH according to the diagnostic criteria of hypertension in the "Chinese Guidelines for the Prevention and Treatment of Hypertension" (2016 Revised Edition) were the case group, and the people with normal blood pressure (83 people) were the control group. Occupational epidemiological investigation was conducted, 5 ml of fasting cubital venous blood was collected, genomic DNA was extracted by phenol-chloroform method, and RAAS gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism method. The distribution differences of genotype and allele frequency between groups were compared, and the relationship between genotype, allele frequency and EH was analyzed.Results:The average age of military secret service personnel was (38.2±5.3) years old, and there was no statistical significance in the average age and the age distribution over 40 years old of the case group and the control group ( P>0.05) . There were significant differences in the distribution of AGT gene M235T locus, ACE gene I/D polymorphism genotype and allele between the case group and the control group ( P<0.05) . The TT genotype with AGT gene M235T locus ( OR=3.28, 95% CI: 1.21-8.91) and DD genotype with ACE gene ( OR=2.86, 95% CI: 1.17-7.00) were risk factors for EH in military secret service personnel. Conclusion:The TT genotype of AGT gene M235T and the DD genotype of ACE gene may be the susceptibility genotypes of military secret service personnel for EH.

Objective:To analyze the relationship between renin-angiotensin-aldosterone system (RAAS) gene polymorphisms and susceptibility to essential hypertension (EH) in military secret service personnel.Methods:In October 2019, military secret service personnel (162 people) who were recuperating in a sanatorium from January to December 2017 were selected as the research subjects, all of whom were Han and male. The patients (79 people) who were diagnosed with EH according to the diagnostic criteria of hypertension in the "Chinese Guidelines for the Prevention and Treatment of Hypertension" (2016 Revised Edition) were the case group, and the people with normal blood pressure (83 people) were the control group. Occupational epidemiological investigation was conducted, 5 ml of fasting cubital venous blood was collected, genomic DNA was extracted by phenol-chloroform method, and RAAS gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism method. The distribution differences of genotype and allele frequency between groups were compared, and the relationship between genotype, allele frequency and EH was analyzed.Results:The average age of military secret service personnel was (38.2±5.3) years old, and there was no statistical significance in the average age and the age distribution over 40 years old of the case group and the control group ( P>0.05) . There were significant differences in the distribution of AGT gene M235T locus, ACE gene I/D polymorphism genotype and allele between the case group and the control group ( P<0.05) . The TT genotype with AGT gene M235T locus ( OR=3.28, 95% CI: 1.21-8.91) and DD genotype with ACE gene ( OR=2.86, 95% CI: 1.17-7.00) were risk factors for EH in military secret service personnel. Conclusion:The TT genotype of AGT gene M235T and the DD genotype of ACE gene may be the susceptibility genotypes of military secret service personnel for EH.

Objective:To analyze the gene variants in patients with primary distal renal tubular acidosis (dRTA), and explore the correlation between the genotype and phenotype.Methods:The Sanger direct sequencing or whole-exome sequencing was used to identify causal variants and the variation pathogenicity was evaluated according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines in 44 dRTA patients (37 families) diagnosed in the Affiliated Qingdao Municipal Hospital of Qingdao University and the Affiliated Hospital of Qingdao University from April 2010 to September 2020. The clinical features of the patients were summarized, and the correlation between the genotype and phenotype was investigated.Results:Seven variants of SLC4A1 gene, 17 variants of ATP6V0A4 gene, and 15 variants of ATP6V1B1 gene were identified in 44 patients with dRTA, and of which 11 variants were new ones. According to ACMG guidelines, the pathogenic, likely pathogenic, benign variants among the 39 variants were 22, 16 and 1, respectively. Nine patients were autosomal dominant hereditary dRTA caused by SLC4A1 gene mutation, 4 patients with autosomal recessive hereditary dRTA complicated with Southeast Asian ovalocytosis and anemia were caused by SLC4A1 gene mutation, and 14 patients caused by ATP6V0A4 gene mutation and 8 patients caused by ATP6V1B1 gene mutation were autosomal recessive hereditary dRTA; Two children with dRTA were found to carry one monoallelic defect in ATP6V1B1, and no causal gene mutation was identified in 7 patients. One patient showed incomplete dRTA, and the other 43 patients showed complete dRTA. The prevalence of sensory neural hearing loss caused by ATP6V0A4 and ATP6V1B1 mutation were 2/14 and 6/10 respectively. The frequency of chronic kidney disease in adults, children and infants were 4/4, 2/4, and 1/36, separately. After the drug treatment based on potassium citrate and sodium citrate, the growth and development (28/40) and electrolyte disturbance (41/44) of most patients were significantly improved. Conclusions:The present study has identified 39 variants of SLC4A1, ATP6V0A4 and ATP6V1B1 genes in 44 patients with dRTA, including 11 novel ones. There is a close relationship between genotype and phenotype in dRTA patients and most patients' conditions were improved after proper treatment. This study enriches the human gene mutation database and provides valuable references for diagnosis, treatment and genetic counseling in patients with dRTA.

Objective: To explore the cause and type of pigmentation in the livers and kidneys of rats caused by a compound Chinese medicine preparation. Methods: The experiment consist of low, medium, and high dose groups and a control group, the Sprague-Dawley rats in these groups were orally given 1.0, 2.0 and 4.0 g/kgbw of a compound Chinese medicine preparation of gardenia and distilled water for 30 days, respectively. The body weight, diet, hematology and histopathology of the rats in each group were observed for changes in pigment metabolism. Results: In the first and second weeks of the experiment, the rats in the low, medium, high dose groups and the control group showed no abnormal symptoms or signs. From the third weekend, the urine of the rats in the high dose group turned thick yellow and green, and the stool color became light. During the experiment, no rats died. There were statistically significant differences in body weights and weight gains among these groups ( P<0.05 ) . There were statistically significant differences in total food utilization, direct bilirubin, r-glutamyl transferase, alkaline phosphatase, and liver/body ratios among these groups ( P<0.05 ). Gross examination revealed that the livers and kidneys of rats in the high dose group were dull and green. Microscopic examination revealed changes in dark pigment particles in the livers and kidneys of rats in the high dose group. Histochemical staining confirmed that pigments in the livers and kidneys were bile pigments. Conclusions At a dosage of 4.0 g/kgbw, a compound Chinese medicine preparation of gardenia can lead to bile pigment deposition in the livers and kidneys of rats due to cholestasis.