ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula（YHJF） on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated， model， low-dose YHJF（4.1 g·kg^-1）， and high-dose YHJF（8.2 g·kg^-1） groups. Except for the sham-operated group， a cecal ligation and puncture（CLP） procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses， while the sham-operated and model groups received an equal volume of physiological saline. After the intervention， the 7-day survival rate of each group was recorded， and spleen samples were collected 72 h post-intervention， and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL） staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay（ELISA） was performed to measure the levels of interleukin（IL）-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes（DEGs） and differential metabolites in the spleen， followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction（Real-time PCR）， flow cytometry， and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice（P0.05）. Compared with the sham-operated group， the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling， with markedly elevated peripheral serum IL-4 and IL-10 levels（P0.01）. Compared with the model group， the high-dose YHJF group showed a reduction in apoptosis of spleen cells， an increase in the spleen index， and a significant decrease in peripheral serum IL-4 and IL-10 levels（P0.05）. Spleen transcriptomics identified 255 DEGs between groups， potentially serving as intervention targets for YHJF. Gene Ontology（GO） enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer（NK） cell-mediated positive immune regulation， cell killing， cytokine production， positive regulation of innate immune cells， and interferon production. Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions， viral protein interactions with cytokines and cytokine receptors， chemokine signaling pathway， and nuclear transcription factor-κB（NF-κB） signaling pathway. Protein-protein interaction（PPI） network analysis identified CD160， granzyme B（GZMB）， and chemokine ligand 4（CCL4） as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention， and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism， arachidonic acid metabolism， glycosylphosphatidylinositol（GPI） anchor biosynthesis， linoleic acid metabolism， and α-linolenic acid metabolism pathways. Verification results showed that， compared with the sham-operated group， the model group exhibited significantly elevated CD160 mRNA expression level in the spleen， along with markedly decreased CCL4 and GZMB mRNA expression， and had a significant increase in CD160 expression on the surface of natural killer T（NKT） cells in the spleen（P0.01）. Compared with the model group， the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen， a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group， CD160 expression on the surface of splenic NKT cells in the model group was significantly increased（P0.01）， while high-dose YHJF intervention significantly reduced CD160 expression（P0.01）. ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160， and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.

ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula（YHJF） on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated， model， low-dose YHJF（4.1 g·kg^-1）， and high-dose YHJF（8.2 g·kg^-1） groups. Except for the sham-operated group， a cecal ligation and puncture（CLP） procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses， while the sham-operated and model groups received an equal volume of physiological saline. After the intervention， the 7-day survival rate of each group was recorded， and spleen samples were collected 72 h post-intervention， and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL） staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay（ELISA） was performed to measure the levels of interleukin（IL）-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes（DEGs） and differential metabolites in the spleen， followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction（Real-time PCR）， flow cytometry， and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice（P0.05）. Compared with the sham-operated group， the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling， with markedly elevated peripheral serum IL-4 and IL-10 levels（P0.01）. Compared with the model group， the high-dose YHJF group showed a reduction in apoptosis of spleen cells， an increase in the spleen index， and a significant decrease in peripheral serum IL-4 and IL-10 levels（P0.05）. Spleen transcriptomics identified 255 DEGs between groups， potentially serving as intervention targets for YHJF. Gene Ontology（GO） enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer（NK） cell-mediated positive immune regulation， cell killing， cytokine production， positive regulation of innate immune cells， and interferon production. Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions， viral protein interactions with cytokines and cytokine receptors， chemokine signaling pathway， and nuclear transcription factor-κB（NF-κB） signaling pathway. Protein-protein interaction（PPI） network analysis identified CD160， granzyme B（GZMB）， and chemokine ligand 4（CCL4） as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention， and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism， arachidonic acid metabolism， glycosylphosphatidylinositol（GPI） anchor biosynthesis， linoleic acid metabolism， and α-linolenic acid metabolism pathways. Verification results showed that， compared with the sham-operated group， the model group exhibited significantly elevated CD160 mRNA expression level in the spleen， along with markedly decreased CCL4 and GZMB mRNA expression， and had a significant increase in CD160 expression on the surface of natural killer T（NKT） cells in the spleen（P0.01）. Compared with the model group， the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen， a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group， CD160 expression on the surface of splenic NKT cells in the model group was significantly increased（P0.01）， while high-dose YHJF intervention significantly reduced CD160 expression（P0.01）. ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160， and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective To understand the current situation of breastfeeding duration in children aged 0-5 years in Yunnan Province,and to explore the influencing factors of breastfeeding duration.Methods Using the data of the 6th National Health Service Survey in Yunnan Province,1582 children aged 0～5 years in Yunnan Province were selected as the research subjects,and the Kaplan-Meier method and Cox regression were used to analyze the influencing factors of breastfeeding duration.Results The mean duration of breastfeeding for children aged 0～5 years in Yunnan Province was 9.29 months,and region,time of complementary food addition,time of suckling and family income were the main factors influencing the duration of breastfeeding.Conclusion The duration of breastfeeding for children aged 0～5 years in Yunnan Province deviates significantly from the recommendations provided by both the World Health Organization(WHO)and China's child breastfeeding guidelines.Given the current situation,the relevant departments must enhance their focus on this issue.

ObjectiveTo study the effects of Huangjing Jiannao granules on learning and memory abilities and cerebral blood flow in the rat model of vascular cognitive impairment （VCI） and to explore the mechanism of Huangjing Jiannao granules in the treatment of VCI. MethodSeventy-two SPF-grade male SD rats were randomly selected， with 12 rats as the sham operation group. The remaining rats were subjected to bilateral carotid artery ligation （2-VO） for the modeling of VCI. According to the randomized block design， the successfully modeled rats were grouped as follows： model， donepezil hydrochloride （0.50 mg·kg^-1）， and low-， medium-， and high-dose （2.36， 4.72， 9.44 g·kg^-1， respectively） Huangjing Jiannao granules. After 6 weeks of treatment， Morris water maze test and new object recognition test were conducted to evaluate the learning and memory abilities of the rats. After continuous gavage for 8 weeks， the cerebral blood flow was recorded by a laser microcirculation blood flow imager， and the survival and injury of hippocampal neurons were observed by Nissl staining. The expression of neuronal nuclear antigen （NeuN） in the hippocampus was detected by immunohistochemistry （IHC）. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay. The protein levels of phosphatidylinositol 3-kinase （PI3K）， phosphorylated protein kinase B （p-Akt）， nuclear factor-κB p65 （NF-κB p65）， and nuclear factor-κB inhibitor α （IκBα） in the hippocampus were determined by Western blot. ResultCompared with the sham operation group， the model group showed weakened learning and memory abilities （P<0.01）， reduced blood flow in the whole brain， forebrain， and hindbrain （P<0.01）， damaged neurons and reduced survived neurons in the hippocampal CA1 region （P<0.01）， down-regulated expression of NeuN （P<0.01）， elevated levels of IL-1β and TNF-α in the serum （P<0.01）， up-regulated protein levels of PI3K， p-Akt， and NF-κB p65 in the hippocampal tissue， and down-regulated protein level of IκBα （P<0.01）. Compared with the model group， medium- and high-dose Huangjing Jiannao granules improved the learning and memory abilities （P<0.05，P<0.01）. High-dose Huangjing Jiannao granules increased the blood flow in the whole brain， forebrain， and hindbrain （P<0.05，P<0.01）， and medium-dose Huangjing Jiannao granules increased the blood flow in the whole brain （P<0.05）. All the doses of Huangjing Jiannao granules increased the number of survived neurons （P<0.05，P<0.01） and up-regulated the protein level of NeuN （P<0.05，P<0.01）. Medium and high-dose Huangjing Jiannao granules lowered the level of TNF-α （P<0.05，P<0.01）， down-regulated the protein levels of PI3K， p-Akt， and NF-κB p65 （P<0.05，P<0.01）， and up-regulated the protein level of IκBα （P<0.01）. ConclusionHuangjing Jiannao granules can improve the learning and memory abilities and promote the recovery of cerebral blood flow in the rat model of VCI induced by 2-VO by regulating the expression of proteins involved in the PI3K/Akt signaling pathway， inhibiting inflammation， and reducing hippocampal neuron injury.

Objective:To systematically estimate the effectiveness of physical activity intervention and Borg perceived exertion on the prevention of gestational diabetes mellitus (GDM), and to provide references for physical activity management during pregnancy.Methods:Databases such as PubMed, Cochrane Library Central Register of Controlled Trails, EMBASE, Scopus, CNKI and Wanfang were searched to collect randomized controlled trials (RCT) focusing on the effect of physical activity intervention on glucose control and pregnancy outcomes in pregnant women. The primary outcome was the incidence of GDM. The secondary outcomes included the 2 hour oral glucose tolerance test (2 h OGTT), gestational weight gain, gestational week of delivery, and neonatal weight. The statistical analysis was performed by R 4.0.2 software. The quality of the literatures was evaluated based on the Cochrane Risk of bias tool.Results:A total of 14 RCTs involving 4 509 participants were included in this meta-analysis. The results of meta-analysis showed that the incidence of GDM ( RR=0.74, 95% CI=0.59-0.93, P<0.01), 2 h OGTT (MD=-0.27, 95% CI=-0.48--0.07, P<0.01), and gestational weight gain (MD=-1.04, 95% CI=-1.91--0.18, P=0.02) in the experimental group were all significantly lower than those in control group, while the neonatal weight (MD=-27.43, 95% CI=-58.77-3.92, P=0.09) and gestational week of delivery (MD=-0.18, 95% CI=-0.93-0.57, P=0.64) showed no significant difference between the two groups. Subgroup analysis showed that Borg rating scale of perceived exertion scored higher than 12 ( RR=0.64, 95% CI=0.46-0.89, P<0.01), physical activity conducted in groups ( RR=0.66, 95% CI=0.46-0.94, P=0.02), intervention organized by fitness specialist ( RR=0.73, 95% CI=0.56-0.95, P=0.02) were associated with the decreased risk of GDM. In addition, the meta-regression result showed that total intervention time more than 2 hours per week (correlation coefficient=-1.06, 95% CI=-1.86--0.27, P<0.01) was the main source of study heterogeneity. Conclusions:Physical activity during pregnancy with Borg rating scale of perceived exertion scored higher than 12 had a positive effect on reducing the incidence of GDM.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To explore the effects of Kaixin Jieyu Pill(KJP)on peroxisome proliferator-activated receptor alpha(PPARα),serum and hippocampal tissue fibroblast growth factor 21(FGF21)and hippocampal tissue fibroblast growth factor receptor 1(FGFR1)in rats with depression model.Methods A rat chronic stress model was prepared using the chronic unpredictable mild stimulus method(CUMS)to observe behavioral changes in depression.Hippocampal FGF21,FGFR1 and liver PPARα protein and mRNA expression levels were measured in hippocampal tissues by western blot and real-time fluorescence quantification(RT-qPCT).Results The expression levels of PPARα,FGF21 and FGFR1's protein and their mRNA were dramatically decreased in the CUMS model rats compared with the normal group(P<0.001).KJP could modify the depressive-like behaviors of rats(P<0.001),upregulate the protein expression level of PPARα,FGF21,and FGFR1(P<0.05,P<0.01,P<0.01);markedly modify the mRNA expression levels of PPARα,FGF21,and FGFR1(P<0.001,P<0.01,P<0.01).Conclusion PPARα/FGF21/FGFR1 pathway may participate in the pathogenesis of depression;upregulation of PPARα/FGF21/FGFR1 pathway may be related to the antidepressant mechanism of KJP.