OBJECTIVE To study the ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury （ALI） based on serum exosomal microRNA （miRNA）. METHODS The rats were randomly divided into a blank group （normal saline）， model group （nomal saline）， and F. suspensa-L. japonica herb pair group （2.55 g/kg）， with 10 rats in each group. Except for the blank group， the other groups were used to establish an ALI model by intratracheal dripping of 5 mg/ mL lipopolysaccharides. After modeling， each group was given relevant medicine/normal saline intragastrically， once a day， for 3 consecutive days. After the last medication， the pathological status of lung tissue was observed； lung wet-to-dry weight ratio and leukocyte counts in bronchoalveolar lavage fluid （BALF） were determined. The levels of inflammatory factors [tumor necrosis factor-α（TNF-α）， interleukin-1β （IL-1β）， IL-10] in BALF were determined. Exosomes were isolated from rat serum， and high- throughput sequencing technology was employed to screen differentially expressed miRNA within the exosomes， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Based on the screened differentially expressed miRNA and the enriched KEGG pathways， in vitro cellular experiments were conducted for validation. RESULTS The animal experimental results demonstrated that after intervention with the F. suspensa-L. japonica herb pair， the wet-to-dry weight ratio， the number of leukocytes in BALF， as well as the levels of TNF-α and IL-1β in BALF of ALI rats were all significantly reduced （P＜0.01）， while the level of IL-10 was significantly increased （P＜0.01）. The results of high-throughput sequencing experiments revealed that the F. suspensa-L. japonica herb pair could significantly up-regulate the expressions of miR-345-3p， miR-194-5p， miR-653-5p， and others in exosomes. Among them， the KEGG pathways involved in the target genes of differentially expressed miRNA included the hypoxia-inducible factor-1（HIF-1） signaling pathway， among others. The results of cellular E-mail：huang.haiying@126.com validation experiments showed that overexpressed miR-345-3p could significantly elevate the level of IL-10 in the cell supernatant （P＜0.01）， while significantly reducing the levels of TNF-α and IL-1β in the cell supernatant， as well as the mRNA and protein expression levels of protein kinase B1， phosphatidylinositol 3- kinase， and HIF-1α （P＜0.01）. CONCLUSIONS F. suspensa-L. japonica herb pair can alleviate inflammatory responses and thereby exert a therapeutic effect in improving ALI by up-regulating the expression of miR-345-3p in serum exosomes and inhibiting the activity of the HIF-1 signaling pathway.

Objective: To explore the associations of moderate to vigorous intensity physical activity (MVPA) and sedentary behavior (SB) among primary and secondary school students and their parents, so as to provide a scientific basis for formulating targeted physical activity promotion strategies for children and adolescents. Methods: From 2021 to 2022, basic information and 24 h movement behaviors of 2 484 pairs of students and their parents were collected from five primary and secondary schools in Haizhu District, Guangzhou City, with a convenient sampling combining with cluster sampling method. Component regression models were constructed to analyze the relationship between parental MVPA, SB and primary and secondary school students MVPA and SB, and a component isochronous substitution model was used to explore the effects of mutual substitution between parental MVPA, residual components (time use components other than SB during the 24 h period), and SB on the behavioral activities of MVPA and SB in primary and secondary school students. Results: Parental MVPA and SB of students in grade 1 to 3 were positively correlated with both students MVPA and SB ( β=0.06, 0.12, P <0.01). The component isochronous substitution model showed that substituting 10 and 20 minutes of MVPA for SB by parents in grade 1 to 3 was associated with an increase in MVPA of students, and substituting 10 and 20 minutes of residual ingredients for SB was associated with a decrease in SB of students, with mean changes of 0.8 (95% CI =0.4-1.2) and 1.4 (95% CI =0.7-2.2) and -1.4 (95% CI =-1.7 to -1.1) and -2.9 (95% CI =-3.4 to -2.3)( P <0.05). No statistically significant associations were observed between parents of students in grades 4 to 6 and 7 to 9 and students physical activity and sedentary behaviour ( P >0.05). Conclusions Parents of students in grades 1 to 3 increases MVPA and decrease SB are beneficial to increase MVPA and decrease SB of students. Parents could promote physical activity among primary and secondary school students, and the intervention gateway should be advanced, with the low grades as the optimal intervention period.

ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos（FF） in the treatment of acute lung injury（ALI） by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week， and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide（LPS） solution by tracheal drip to establish an ALI model. After successful model establishment， the rats were randomly divided into the model group， the FF low-dose group（3.0 g·kg^-1）， the FF high-dose group（6.0 g·kg^-1）， and the dexamethasone group（5 mg·kg^-1）， with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution， and the blank group and the model group were gavaged with an equal amount of saline， treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin（HE） staining， wet/dry mass ratio（W/D） of the lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， combined with multivariate statistical analysis， the potential biomarkers of FF in treating ALI were screened by variable importance in the projection（VIP） value>1， P<0.05 from t-test， and log₂fold change（FC）>1 or log₂FC<-1. Kyoto Encyclopedia of Genes and Genomes（KEGG） database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate（S1P）， phosphatidylinositol 3-kinase（PI3K）， protein kinase B1（Akt1）， and phosphorylated Akt1（p-Akt1） were examined by Western bolt. The expression levels of interleukin（IL）-6， IL-1β， and tumor necrosis factor（TNF）-α in BALF were detected by enzyme-linked immunosorbent assay（ELISA）. ResultsCompared with the blank group， rats in the model group showed ALI pathological features such as alveolar lumen dilatation， interstitial hemorrhage and massive inflammatory cell infiltration， and the protein concentration in BALF and W/D of the lung tissues were significantly elevated（P<0.01）. Compared with the model group， the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats， and the protein concentration in BALF and W/D were significantly decreased（P<0.05）， and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways， including arginine biosynthesis， sphingomyelin metabolism， alanine， aspartate and glutamate metabolism， taurine and hypotaurine metabolism， α-linolenic acid metabolism， niacin and nicotinamide metabolism， and retinol metabolism. The results of Western bolt and ELISA showed that， compared with the blank group， the model group exhibited significantly elevated expression levels of S1P， PI3K， Akt1 and p-Akt1 proteins in the lung tissues， as well as increased expression levels of IL-6， IL-1β and TNF-α in BALF（P<0.01）. Compared with the model group， the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group（P<0.05， P<0.01）. ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism， and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.

In the special periods of puberty,menstruation,pregnancy,postpartum,and perimenopause of the female life,the drastic changes in qi and blood of the women cause the redistribution of qi,blood,yin and yang in those periods,which easily leads to various disordered states of disharmony between nutrient qi and defensive qi,disharmony between qi and blood,and imbalance of yin and yang.By analyzing the mechanism of the disharmony between nutrient qi and defensive qi in the special periods of puberty,menstruation,pregnancy,postpartum,and perimenopause of the female life,this paper proposes the approach of harmonizing nutrient qi and defensive qi to treat menstrual disorders,leukorrheal disease,gravid trouble,and parturition problems.Moreover,It is recommended that Guizhi Tang(Cinnamomi Ramulus Decoction),the chief of ZHANG Zhong-Jing's prescriptions and having the actions of releasing muscles and harmonizing nutrient qi and defensive qi,and activiting qi and harmonizing yin and yang,can be used to treat gynecological diseases through the modification.The utilization of Guizhi Tang for the treatment of gynecological diseases at various periods of women's lives will expand the application of classical prescriptions in treating gynecological diseases.

Objective To investigate the bidirectional causal relationship between endometriosis and thyroid cancer using bidirectional two-sample Mendelian randomization(MR).Methods Ge-nome-wide association study(GWAS)data for endometriosis were obtained from the FinnGen R11 database,and GWAS data for thyroid cancer were sourced from the European Bioinformatics Institute(EMBL-EBI).Single nucleotide polymorphisms(SNPs)that met the requirements were selected as instrumental variables.The inverse variance weighted(IVW)method was employed as the primary analytical approach,supplemented by MR-Egger regression,weighted median method,simple model,and weighted model results.Cochran's Q test,MR-Egger regression intercept analysis,and the leave-one-out method were used to assess the robustness of the results.Results Ultimately,25 SNPs high-ly associated with endometriosis and 3 SNPs highly associated with thyroid cancer were included in this study.The IVW analysis results of the forward MR analysis indicated no significant causal rela-tionship between endometriosis and the risk of thyroid cancer(P=0.50,OR=1.06,95％CI:0.88 to 1.29).This result was also supported by MR-Egger regression,simple model,weighted model,and weighted median analyses(P＞0.05).The IVW analysis results of the reverse MR analysis similarly showed no significant causal relationship between thyroid cancer and the risk of endometrio-sis(P=0.09,OR=1.03,95％CI,0.99 to 1.06).The findings from MR-Egger regression,sim-ple model,weighted model,and weighted median analyses all supported this conclusion(P＞0.05).Conclusion The MR analysis doesn't show a significant bidirectional causal relationship between endometriosis and thyroid cancer.

BACKGROUND:Among the pathogenic factors of cervical spondylosis,herniation of the intervertebral disc,dislocation of the facet joint and the stenosis of the intervertebral foramen are important factors leading to symptoms in patients.Moreover,inappropriate manipulation may aggravate the possibility of cervical disc rupture,leading to exacerbation of symptoms in patients. OBJECTIVE:To compare the effect between sagittal cervical manipulation and traditional cervical rotation manipulation on the area of the intervertebral disc,facet joint and intervertebral foramen at the operative segment by the finite element analysis. METHODS:The neck CT data of a male volunteer with a normal neck were selected and imported into Mimics 17.0 three-dimensional reconstruction software.Geo-magic Studio 12.0,Solidworks 2017 and Ansys Workbench 17.0 software were used for the construction of the finite element model of cervical vertebrae(C3-6)including intervertebral disc and articular cartilage.The lower end plate of the C5 vertebral body was fixed.A uniformly distributed vertical downward 50 N load was applied on the upper surface of the upper vertebral body(C3).The stress,deformation and deformation direction of the C4-5 intervertebral disc,joint capsule stress,the displacement of facet joints and the area of bilateral intervertebral foramen were compared between sagittal cervical manipulation and traditional rotation reduction. RESULTS AND CONCLUSION:(1)When using the rotation technique,the maximum normal equivalent stress(von Mises stress)of the C4-5 disc was 8.06 MPa;the total deformation was 1.05 mm,and the fiber ring expanded to the left and outside.When using the sagittal tip lifting technique,the maximum normal equivalent stress(von Mises stress)of the C4-5 disc was 2.60 MPa;the total deformation was 0.90 mm,and the fiber ring expanded to the left and back.Compared with the rotation technique,the pressure of the cervical manipulation technique on the disc was less(about 32.3%of the rotation technique),and the deformation degree of the disc was also light(about 85.7%of the rotation technique).(2)When the rotation technique was used,the maximum stresses of the left and right articular capsule ligaments were 0.37 MPa and 1.69 MPa,respectively.The overall displacement of the facet joint was 2.21 mm.The area of the right intervertebral foramen decreased by about 3.8%and the area of the left intervertebral foramen increased by about 0.9%.When the sagittal end lifting manipulation was performed,the maximum stresses of the left and right articular capsule ligaments were 0.27 MPa and 1.70 MPa,respectively;the overall displacement of the facet joint was 1.63 mm;the area of the right intervertebral foramen increased by about 2.6%,and the area of the left intervertebral foramen decreased by about 0.9%.Compared with rotation manipulation,sagittal end lifting manipulation had fewer changes in the displacement of facet joint,joint capsule stress and intervertebral foramen area,so it was safer to operate.(3)In conclusion,compared with cervical rotation manipulation,sagittal end lifting manipulation has fewer changes in facet joint displacement,intervertebral disc stress/deformation degree,joint capsule stress,and foraminal area.In clinical practice,more appropriate manipulation should be selected based on biomechanical results after an accurate assessment of patients'conditions.

Objective: To analyze the epidemiological and molecular characteristics of norovirus outbreaks in schools in Xicheng District of Beijing from 2017 to 2022, so as to provide evidence for the prevention and control of norovirus outbreaks in schools. Methods: Data of norovirus outbreaks in schools in Xicheng District, Beijing during 2017 to 2022 were collected and analyzed by descriptive epidemiological methods. Realtime PCR was used to detect the nucleic acid of group GⅠand GⅡnorovirus, the positive norovirus nucleic acid samples were sent to Beijing Center for Disease Control and Prevention for molecular typing. Results: From 2017 to 2022, 185 norovirus outbreaks were reported in schools in Xicheng District, including 166 cluster outbreaks and 19 outbreaks. A total of 2 044 cases were reported, with a total attack rate of 13.92%. There were two peaks in the outbreak time, which were from March to June after the spring semester and from October to December after autumn semester. Primary schools were the most common place of occurrence (101 cases), followed by nursery institutions (68 cases) and secondary schools (16 cases). There were statistically significant differences in the incidence rates among different sites(12.37%, 22.78%, 8.47%, χ2=263.34, P<0.01). There were significant differences in the incidence of vomiting, diarrhea, nausea and stomachache among different students (χ2=263.33, 90.58, 20.42, 30.29, P<0.01). Vomiting was the main symptom in primary school and nursery school children (96.41%, 98.28%), and the diarrhea rate was higher in middle school students (68.22%). The outbreaks were mainly caused by type GⅡ norovirus. The genotype from 2017 to 2021 showed the characteristics of diversity, mainly GⅡ.2[P16], but there was no significant advantage for the GⅡ.2 [P16] during 2019 to 2021. Conclusions The norovirus outbreak in schools in Xicheng district of Beijing from 2017 to 2022 are mainly caused by GⅡ type genome. The main genotype is GⅡ.2[P16]. Norovirus infection mainly occurred in primary schools and kindergartens. For the vulnerable populations, it is necessary to improve the capacity to early identification, student infectious disease management, active infection control and prevention measures, and pathogen surveillance and sporadic case monitoring.

Objective To understand the molecular epidemiological characteristics of Norovirus outbreaks and the genome evolution of Norovirus epidemic strains in Hainan Province from 2020 to 2022.Methods The information and samples have been collected from the norovirus outbreaks from 2020 to 2022.Norovirus was detected by using the real-time PCR in these samples,then the detected sequences were amplified the analyzed.The Norovirus se-quences of 8 strains had been amplified and analyzed.Results From 2020 to 2022,39 gastroenteritis outbreaks were reported,and 25 outbreaks caused by Norovirus which mainly occurred in childcare institutions and schools(20/25,80％).The Norovirus outbreaks were mainly concentrated in counties around Haikou(northeast),which including Ding'an(5 cases),Wenchang(4 cases),Chengmai(4 cases),and Lingao(3 cases);following by western regions which included Baisha(2 cases),Ledong(2 cases),and Dongfang(3 cases).1 case was in Wanning in the southeast.Among individuals aged 2-17,the positive proportion of Norovirus in males was higher than that in females.Among individuals aged over 55,the proportion of Norovirus positive in females was higher than that in males.The gender of positive samples among individuals aged 18-40 was related to their profession.According to RT-PCR typing and sequencing,GⅡ group Norovirus were classified in13 outbreaks.There were 4 genotypes detected.GⅡ.2[P1 6]was the main epidemic strain with 60％(9/13),and the other three genotypes were GⅡ.4 Sydney[P31](15.4％,2/13)GⅡ.4 Sydney[P16](7.7％,1/13)and GⅡ.3[P12](7.7％,1/13).Further genic analysis of 8 Norovirus strains showed that all of them were still in the same branch as the previ-ous strain,and all exhibited a certain amount of amino acid variation.Conclusion Norovirus is the main pathogen of gastroenteritis outbreaks in Hainan province,and the main epidemic strain is GⅡ.2[P16].It is necessary to continue to strengthen the monitoring that provides scientific evidence for the prevention and control of norovirus out-breaks in Hainan region.

Objective To assess the effects of low-dose esketamine on the median effective dose(ED50)of ciprofol for anesthesia induction in painless gastrointestinal endoscopy.Methods Fifty-nine pa-tients underwent elective painless gastrointestinal endoscopy,26 males and 33 females,aged 18-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups by random number table method:esketamine combined with ciprofol group(group EC,n = 29)and ciprofol group(group C,n = 30).Group EC received intravenous injection of esketamine 0.3 mg/kg and group C received the same amount of normal saline 2 minutes before administration of ciprofol.The initial anesthesia induction dose of ciprofol was 0.4 mg/kg.If a positive reaction occurs during the examination,the next patient will receive an increase dose of propofol 0.04 mg/kg,otherwise will decrease by propofol 0.04 mg/kg.The positive reaction was defined that the patient's BIS can not be decreased to 60 2 minutes after anesthesia induction,or the cough or body movement reaction occur at level 2 or above when entering the mirror.The dosage of ciprofol,recovery time,discharge time,the occurrence of intraoperative and postoperative adverse reactions were recorded.The ED50,95%effective dose(ED95)and 95%confidence interval(CI)of the two groups were calculated by Probit probability regression analysis.Results Compared with group C,the dosage of ciprofol,the incidence of hypotension and frequency of administration of vasoactive drugs during the exami-nation process in group EC were significantly reduced(P＜0.05).The ED50 of ciprofol for anesthesia in-duction in painless gastrointestinal endoscopy in group EC was 0.21 mg/kg(95%CI 0.12-0.25 mg/kg)and the ED95 was 0.32 mg/kg(95%CI 0.26-0.39 mg/kg).The ED50 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group C was 0.37 mg/kg(95%CI 0.32-0.40 mg/kg)and the ED95 was 0.48 mg/kg(95%CI 0.43-0.54 mg/kg).The ED50 and ED95 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group EC was significantly lower than that in group C(P＜0.05).There was no significant difference in other frequency of adverse events between the two groups.Conclusion Esketamine 0.3 mg/kg can reduce the ED50 of ciprofol in painless gastrointestinal endoscopy and reduce the dosage of ciprofol during the examination process,which is safe for painless gastrointestinal endoscopy with stable intraoperative circulation.

ObjectiveSerum metabolomics of acute lung injury（ALI） in rats was conducted using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） to explore the similarities and differences in the mechanism of Qingqiao（harvested when the fruits of Forsythiae Fructus were initially ripe and still green in color） and Laoqiao（harvested when the fruits of Forsythiae Fructus were ripe） in the treatment of ALI. MethodA total of 24 SD male rats were acclimatized and fed for 1 week， 6 of them were randomly selected for the blank group and 18 for the experimental group. The ALI model was induced in the experimental group by tracheal intubation with lipopolysaccharide（LPS）. After successfully constructing the ALI model， these rats was randomly divided into model group， Qingqiao group and Laoqiao group， with 6 rats in each group. The Qingqiao and Laoqiao groups were administered orally once a day at a dose of 1.5 g·kg^-1， while the blank and model groups received an equivalent volume of saline for 3 consecutive days. The pathological conditions of rat lung tissues were comprehensively assessed by hematoxylin-eosin（HE） staining， wet-to-dry mass ratio（W/D） of lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. The levels of interleukin（IL）-6， IL-1β and tumor necrosis factor（TNF）-α in BALF were quantified using enzyme-linked immunosorbent assay（ELISA）. UPLC-Q-TOF-MS was used to identify and analyze the chemical compositions of Qingqiao and Laoqiao， and serum metabolomics of rats in each group was analyzed， combined with multivariate statistical analysis with variable importance in the projection（VIP） value>1， P<0.05 from t-test， and fold change（FC）≥1.5 or FC≤0.5 to screen the differential metabolites Qingqiao and Laoqiao for the treatment of ALI. The Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used in combination with MetaboAnalyst for the metabolic pathway analysis of the screened differential metabolites. ResultCompared with the blank group， rats in the model group exhibited enlarged alveolar lumen， ruptured alveoli， interstitial hemorrhage， bronchial exudation of a large number of neutrophils and erythrocytes， and a significant increase in the protein concentration in the BALF and the W/D value of the lung tissues（P<0.01）. In contrast， compared with the model group， rats in the Qingqiao group and the Laoqiao group showed reduced bronchial hemorrhage in the lungs， and the protein concentration in the BALF and the W/D value of the lung tissues were significantly decreased（P<0.01）， the lung injury was significantly alleviated， but more obvious in the Qingqiao group. Compared with the blank group， the expression levels of IL-6， IL-1β and TNF-α in the BALF of the model group were significantly higher（P<0.01）. Additionally， compared with the model group， the expression levels of IL-6， IL-1β and TNF-α in the Qingqiao and Laoqiao groups were significantly lower（P<0.01）. The chemical composition analysis of Qingqiao and Laoqiao revealed that 63 components were detected in Qingqiao and 55 components were detected in Laoqiao， with 47 common components， 16 components unique to Qingqiao and 8 components unique to Laoqiao. Characterizing the differences in serum metabolomics in rats， 19 and 12 metabolites were called back by Qingqiao and Laoqiao， respectively. The metabolic pathway enrichment analysis showed that Qingqiao exerted its therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， phenylalanine metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， glycerophospholipid metabolism， α-linolenic acid metabolism， and arachidonic acid metabolism， and Laoqiao exerted therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， arachidonic acid metabolism， sphingolipid metabolism， phenylalanine metabolism， ascorbate and aldarate metabolism， and glycerophospholipid metabolism. ConclusionQingqiao and Laoqiao have therapeutic effects on ALI， and Qingqiao is more effective. Both of them can play a therapeutic role in ALI by regulating amino acid metabolism and lipid metabolism， but the metabolic pathways affected by them are different.