Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.

Objective To investigate the reliability and feasibility of spectral entropy in evaluate the effectiveness of analgesic sedation in patients with ischemic stroke.Methods A total of 64 patients with acute ischemic stroke admitted to Hongqi Hospital Affiliated to Mudanjiang Medical University from July 2021 to November 2022 were selected as study objects,and the included patients were divided into control group and experimental group according to random number table method,with 32 cases in each group.Patients in control group adjusted analgesia and sedation regimen according to Richmond agitation-sedation scale(RASS)score and critical-care pain observation tool(CPOT)score.Patients in experimental group adjusted the analgesic and sedation regimen according to the results of spectral entropy.The vital signs,C-reactive protein(CRP),dose of sedative and analgesic drugs and incidence of adverse reactions were compared between two groups.The correlation between spectral entropy and RASS score and CPOT score was used Spearman correlation analysis.Results The spectral entropy values were positively correlated with the RASS score and CPOT score,respectively(r=0.719,0.556,P<0.001).There were no significant differences in mean arterial pressure and percutaneous arterial oxygen saturation between two groups at different time points(P>0.05).The heart rate at T3 in experimental group was significantly lower than that in control group(P<0.05).At T1,T2 and T3,CRP levels in experimental group were significantly lower than those in control group(P<0.05).The dosage of sufentanil and midazolam in experimental group were significantly lower than those in control group(P<0.05).The incidence of adverse reactions in experimental group was significantly lower than that in control group(12.50%vs.34.38%,χ2=4.267,P=0.039).Conclusion Spectral entropy can be used as an objective method to monitor the depth of analgesia and sedation in patients with ischemic stroke,and has a good correlation with RASS score and CPOT score,which can reduce the incidence of adverse reactions,effectively avoid stress reactions,and reduce the application of analgesia and sedation drugs.

In recent years, externalizing behavior problems in children have become increasingly prevalent. Research has shown that early parenting interventions can effectively improve children′s externalizing behaviors. The dyadic parent-child interaction coding system (DPICS) is a validated, evidence-based tool for assessing and guiding parent-child interactions in families with children aged 3 - 8 years. This article reviews the current status and influence mechanisms of parent-child interactive interventions using DPICS, aiming to provide richer evidence for interventions targeting children′s behavior problems.

Objective:To analyze the differentially expressed genes of human respiratory syncytial virus (RSV) subtype A genotype ON1, a predominant genotype in Beijing, after infecting A549 cells using transcriptomic sequencing, and provide potential targets for RSV prevention and treatment.Methods:A local strain (61397-ON1) identified by whole-genome sequencing as ON1 genotype of RSV subtype A was selected to infect A549 cells. Total mRNA was extracted, and the differentially expressed genes in infected and uninfected A549 cells were screened by transcriptomic sequencing. GO analysis and KEGG pathway analysis were performed. Besides, six genes with differential expression ratio greater than two times were randomly selected for qRT-PCR verification.Results:There were 1 632 differentially expressed genes between infected and uninfected A549 cells, of which 807 genes were up-regulated and 825 genes were down-regulated. The differentially expressed genes were mainly involved in immune response-related biological processes such as cytokine response and positive regulation of MAPK cascades, and were enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, p53 signaling pathway, TNF signaling pathway, IL-17 signaling pathway and NF-κB signaling pathway. The results of qRT-PCR for six differentially expressed genes were consistent with the trend of transcriptome data.Conclusions:The differentially expressed genes of RSV A subtype ON1 genotype after infecting A549 cells are mainly involved in cytokine response and immune-related signaling pathways. This study provides basic data for further study of the molecular mechanism of RSV infection and the development of prevention and treatment strategies.

Objective:To investigate the value of ultrasonic measurement of the ratio of optic nerve sheath diameter (ONSD) to eyeball transverse diameter(ETD) in the diagnosis and prognosis of intracranial hypertension in patients with craniocerebral trauma.Methods:A total of 120 patients with craniocerebral trauma treated in the Xingtai General Hospital of North China Medical and Health Group from December 2021 to January 2023 were perspectively selected, and they were divided into normal intracranial pressure group (73 cases) and intracranial hypertension group (47 cases) according to the results of intracranial pressure measurements, and the intracranial hypertension group was divided into good prognosis group (20 cases) and poor prognosis group (27 cases) according to the follow-up prognosis. The efficacy of ONSD, ETD and ONSD/ETD in intracranial hypertension diagnosis and prognosis assessment were analyzed by receiver operating characteristic (ROC) curve. Kaplan-Meier method was used to evaluate the 6-month risk of adverse prognosis of patients, and the comparison was made by Log-rank test.Results:The levels of intracranial pressure, ONSD, ONSD/ETD in the normal intracranial pressure group were lower than those in the intracranial hypertension group: (130.73 ± 23.63) mmH 2O (1 mmH 2O = 0.009 8 kPa) vs. (270.11 ± 35.78) mmH 2O, (5.47 ± 0.29) mm vs. (5.78 ± 0.44) mm, 0.246 ± 0.018 vs. 0.263 ± 0.018, there were statistical differences ( P<0.05). The scores of Glasgow Coma Scale (GCS), intracranial pressure, ONSD, ONSD/ETD in the good prognosis group were lower than those in the poor prognosis group: (5.50 ± 1.24) scores vs. (6.41 ± 1.34) scores, (256.15 ± 30.23) mmH 2O vs. (280.44 ± 36.56) mmH 2O, (5.62 ± 0.40) mm vs. (5.90 ± 0.44) mm, 0.254 ± 0.014 vs. 0.270 ± 0.017, there were statistical differences ( P<0.05). ROC curve analysis results showed that the area under the curve (AUC) of ONSD and ONSD/ETD for diagnosing intracranial hypertension in patients with craniocerebral trauma were 0.718 and 0.765, respectively, and the critical values were 5.87 mm and 0.263, respectively. The AUC of ONSD and ONSD/ETD predicting prognosis of intracranial hypertension patients was 0.677 and 0.763, respectively, and the critical values were 5.90 mm and 0.267, respectively. Grouped by the threshold of ONSD/ETD for the prognosis of intracranial hypertension (0.267), the incidence of adverse prognosis in ONSD/ETD > 0.267 group was higher than that in the ONSD/ETD≤0.267 group, there was statistical difference ( P<0.05). Conclusions:ONSD/ETD can be used as an index for diagnosis and prognosis of intracranial hypertension.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective To evaluate the short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure. Methods The patients undergoing modified Bentall procedure with the remnant aortic wall as a sleeve to cover the sewing area of composite valved graft and the aortic annulus for proximal hemostasis between March 2021 and March 2022 in Shenzhen Fuwai Hospital were enrolled. Short-term results were assessed by cardiopulmonary bypass time, aortic clamping time, mechanical ventilation time, ICU stay, postoperative hospital stay, effusion drainage on the first postoperative day, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), and follow-up results. Results A total of 14 patients were collected, including 12 males and 2 females, with a mean age of 55.33±10.57 years. There was no postoperative or follow-up death. Cardiopulmonary bypass time was 147.90±21.29 min, aortic clamping time was 115.70±15.23 min, mechanical ventilation time was 19.42±8.98 h, ICU stay was 99.08±49.42 h, and postoperative hospital stay was 16.33±2.74 d. Thoracic drainage volume was 333.33±91.98 mL on the first postoperative day. Only 2 patients required blood transfusion (4.5 U and 2 U, respectively). During the follow-up of 6.17±3.69 months, there was no death, no aortic or valve-related complications. There was statistical difference in the LVEDD between preoperation and before discharge after surgery (P＜0.001), and between half a year after surgery and before discharge after surgery (P＜0.001). There was a little decrease of LVEF before discharge after surgery compared with preoperative LVEF, but there was no statistical difference (P=0.219). There was no statistical difference in the LVEF half a year after operation compared with that before operation (P=1.000). Conclusion Sleeve wrapping technique using remnant aortic wall in modified Bentall procedure has good short-term results. This modification may be a simple, effective way in controlling proximal bleeding.

Objective To analyze the correlation of interferon-induced protein with tetratricopeptide repeats 1(IFIT1)with immune infiltration and prognosis of ovarian cancer(OC).Methods GEO database was employed to select the tumor immune related genes,and Kaplan-Meier and Prognoscan databases were used to identify the genes significantly associated with OC prognosis.The differential expression of IFIT1 between OC tissue and normal tissue were confirmed with GEPIA,Human Protein Atlas,and Timer databases.The expression level of IFIT1 in OC tissues with different grades and stages were analyzed in the UALCAN database.In addition,based on David database,GO enrichment analysis was used to analyze the interacting genes and proteins of IFIT1 in the String and Genemania databases.Timer and Tisidb databases verified the correlation between IFIT1 and immune cells mutually.Finally,after IFIT1 knockdown xenograft model was constructed based on lentiviral vector of IFIT1 shRNA,the tumor growth was observed in the transplanted nude mice,and infiltration of neutrophils was observed with immunohistochemical assay.Results FIT1,a tumor immune gene,selected from the GEO database,Kaplan-Meier and Prognoscan databases,was negatively correlated with the OC prognosis.GEPIA,Human Protein Atlas,Timer database,and UALCAN database indicated that the expression level of IFIT1 was significantly higher in the OC tissues than the normal ovarian tissues,and had no obvious correlation with tumor stage and grade.Analysis in String,Genemania,and David database found the interaction genes and proteins of IFIT1 were enriched in activation of 2'-5'oligonucleotide synthase,virus defense,and innate immunity,and other processes.The Timer database presented that IFIT1 was positively correlated with the infiltration of CD8+T cells,B cells,dendritic cells,neutrophils,and macrophage in OC,with neutrophils having the most significant correlation.Tisidb and GSCA also confirmed the positive correlation between IFIT1 and neutrophil infiltration in OC(P＜0.05).RT-qPCR and Western blotting confirmed that IFIT1 knockdown resulted in suppressed tumor growth in OC cells xenograft nude mice(P＜0.05)and reduced neutrophil infiltration in the xenograft tissues.Conclusion IFIT1 may influence the malignant progression of OC by promoting neutrophil infiltration.

Dong qi,referring to beating beside the navel,was proposed for the first time by Nan Jing."Beating above the navel""beating below the navel",and"beating below the heart"in Shanghan Lun all belong to the category of Dong qi.The pathogenesis of Dong qi can be learned from Shanghan Lun.Yang deficiency of the heart,spleen,and kidney,with qi failing to transform body fluids,results in fluid retention.Fluid retention is the key etiological factor of Dong qi.Although there is an exterior pattern with Dong qi,the exterior-releasing and purgative method cannot be used for treatment,or the patient will be impaired of yang and exhausted of yin,fluid circulation will be disturbed,and so on.Reinforcing yang qi to drain water retention is the treatment principle of Dong qi.The coupled medicines of Fuling and Guizhi were commonly used by ZHANG Zhongjing to treat Dong qi.This reflects the treatment principle of strengthening the spleen and warming yang for transforming qi to circulate body fluids.ZHANG Bi,a physician from the Yuan Dynasty who learned from ZHANG Zhongjing,thought that the treatment of Dong qi was based on the method of cultivating earth to restrain water and taking into account the ascending,descending,entering,and exiting of qi of the liver,heart,lung,and kidney while tonifying the spleen,and then created Baoming Siqi Powder(Zhiqiao,Fuling,Fangkui,and Qianhu Powder)for the treatment of Dong qi,which is of great significance to the clinic.

The basic diagnostic and treatment principles of traditional Chinese medicine are the pattern-differentiation-deduced pathogenesis and treatment based on examination of the pathogenesis.Shanghan Lun established a system of pattern differentiation of six meridians,systematically summarized the evolution laws of exogenous febrile disease,and discussed miscellaneous diseases as exogenous diseases.It contains 112 classic formulas and advocates that"those whose disease corresponds to the formulas should take them accordingly",combining disease differentiation and pattern differentiation,containing not only the knowledge of treatment based on pattern identification,but also the profundity of pattern-differentiation-deduced pathogenesis.Based on the original meaning of"pathogenesis",from the three angles of"subtle meaning","core meaning",and"appropriate meaning",this paper exemplifies the concept of pattern differentiation for six meridians in Shanghan Lun,analyzes the relationship and connotation of formula patterns of classical formulas in Shanghan Lun by"taking pattern with formulas",and explores the concept of pattern-differentiation-deduced pathogenesis in Shanghan Lun.This paper emphasizes that during the clinical practice of traditional Chinese medicine,it is important(i)to deduce the pathogenesis based on pattern differentiation,understand symptoms upon first onset,and deduce the pathogenesis before symptoms appear,thereby treating the disease at an early stage;(ii)to identify the most important concepts,solve complications with simple method,discern the core of the disease,and treat the entire body;and(iii)to optimize timing,act quickly,take advantage of opportunities,accept outcomes,and provide judicious guidance to patients.This paper serves to interpret Shanghan Lun based on pattern-differentiation-deduced pathological mechanism and provides ideas and inspiration for applying the theory of Shanghan Lun to guide clinical practice.