Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma： A Review / 中国实验方剂学杂志

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Screening and correction of myopia in children and adolescents from the Gannan region / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To understand the screening and correction of myopia in children and adolescents from the Gannan region of Gansu Province, and to provide guidance for the prevention and control of myopia.METHODS: A cross-sectional stratified cluster sampling study was conducted to select 2 kindergartens and 12 primary and secondary schools in Hezuo City and Zhouqu County, Gannan region of Gansu Province, two classes were randomly selected from each grade, and the whole class was used as a unit for screening. The screening and correction of myopia in children and adolescents were collected for statistical analysis.RESULTS: A total of 5 072 children and adolescents were selected, and 4 806 valid data were finally included after excluding unqualified records. The overall prevalence of myopia was 45.55%, and the prevalence of myopia showed an increasing trend with the increase of grade(P<0.001). The prevalence of myopia in girls(48.66%)was higher than that in boys(42.18%; P<0.001). The prevalence of myopia increased with age(P<0.001), and the age group of 10-12 years old was the fastest growing for myopia, increasing from 25.62% to 60.57%. Furthermore, moderate myopia and high myopia showed an increasing tread with the increase of the grade(all P<0.001). The overall glasses wearing rate of the Gannan region was 28.55%, with a full correction rate of 50.72%, and the glasses wearing rate showed an increasing trend with the increase of grades(P<0.001). The glasses wearing rate of female students(30.84%)was higher than that of male students(26.69%; P=0.008). The full correction rates of low, moderate and high myopia in junior high were the lowest among the 3 phases of studying. The full correction rate of high myopia was the lowest in all phases of studying.CONCLUSION: The prevalence of myopia in children and adolescents from the Gannan region is lower than the national average, but the myopia of children and adolescents is still a trend of young age and high incidence, and the glasses wearing rate of myopia and full correction rate are low.

Pharmacological Effect of Phellodendri Chinensis Cortex and Active Components on Gout： A Review / 中国实验方剂学杂志

Gout is a metabolic disease closely associated with hyperuricemia and urate deposition. Because of the complex pathogenesis， high morbidity， multiple complications， and increasingly young patients， gout has received worldwide attention. Currently， western medicine mainly treats gout by lowering the uric acid level and reducing inflammation， which， however， causes serious adverse reactions and has contraindications. Phellodendri Chinensis Cortex （PCC） is the dried bark of Phellodendron chinense， with the effects of clearing heat， drying dampness， purging fire， detoxifying， and treating sores. Studies have shown that PCC and its active components have anti-inflammatory， pain-relieving， uric acid-lowering， and anti-gout activities， with extensive sources and high safety. PCC and its active components could prevent and treat gout through multi-targets and multi-pathways， whereas the systematic review remains to be carried out. Therefore， this paper summarized the pharmacological activities and mechanisms of PCC and its active components in the treatment of gout. The available studies have shown that PCC and its active components exert the anti-gout effect by lowering the uric acid level， reducing inflammation， alleviating oxidative stress， and regulationg intestinal flora， and protecting the kidneys. Particularly， the active components represented by alkaloids contribute obviously to the therapeutic effect of of PCC. Herein， we analyzed the problems and future development of the research on PCC， aiming to provide theoretical support and a scientific basis for the research and development of new drugs against gout.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Preparation, pharmacokinetics and pharmacodynamics of curcumin nano emulsion / 药学实践杂志

Objective To explore the pharmacokinetic properties of curcumin nano emulsion and its pharmacodynamic effects on hyperlipidemia in rats. Methods The method for determination of curcumin was established by HPLC-MS. The pharmacokinetics characteristics of curcumin nano emulsion oral administration system were investigated. SD rats were used as model animals to establish hyperlipidemia animal models, and the pharmacodynamic effects of curcumin nano emulsion on hyperlipidemia induced by high fat diet was preliminarily investigated. Results The results of pharmacokinetic studies in vivo showed that the relative bioavailability of curcumin nano emulsion was 313.47% with bulk drug group as the reference preparation. The relative bioavailability of curcumin nano emulsion was 279.52 % with tablets as reference preparation. Cmax of curcumin nano emulsion group was 201.48 % of that of bulk drug group and 193.02 % of that of tablet group, and had higher MRT value (183.52 % of that of bulk drug group and 154.21 % of that of tablet group) than bulk drug group and tablet group. Pharmacodynamics research results showed that curcumin nano emulsion oral administration system could significantly reduce the levels of triglyceride and LDL-c in serum of model rats, and relieve liver lipid deposition and liver injury caused by high-fat diet in model animals. Conclusion The oral administration system of curcumin nano emulsion could effectively improve the bioavailability of curcumin, which has a good hypolipidemic effect. It also could control the weight gain of hyperlipidemia rats and improve the changes of liver coefficient caused by lipid metabolism disorder.

Traditional Chinese Medicine Intervention in Membranous Nephropathy Based on Podocyte Injury： A Review / 中国实验方剂学杂志

Membranous nephropathy， an autoimmune kidney disease with glomerular podocyte injury as the core mechanism， is a common pathological type of adult nephrotic syndrome and has become the main cause of end-stage renal disease in China. Podocytes are terminally differentiated cells that play an important role in maintaining the structural and functional stability of glomeruli and are molecular barriers for protein filtration. Glomerular filtration membrane injury induced by podocyte injury is an important cause of massive proteinuria. Persistent or aggravated proteinuria may prolong the course of membranous nephropathy. It is believed that podocyte destruction in membranous nephropathy is mainly related to oxidative stress， autophagy dysregulation， abnormal expression of podocyte marker proteins， chronic inflammation， epithelial-mesenchymal cell transdifferentiation， and so on. At present， western medicine mostly uses immunosuppressants and hormones for treatment according to its pathological stage， but there are certain adverse reactions. Traditional Chinese medicine （TCM） has made some achievements in the prevention and treatment of membranous nephropathy. In recent years， studies have found that many Chinese medicines can affect the occurrence and development of membranous nephropathy in different links by acting on multiple targets in the human body， with manifest advantages. This paper overviewed the podocyte injury mechanism in membranous nephropathy and summarized the treatment of membranous nephropathy with Chinese medicine monomers， compounds， and Chinese patent medicines in intervening related target pathways， aiming to provide a basis for the clinical treatment， basic research， and targeted drug development of TCM against membranous nephropathy.

Relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders / 中国学校卫生

Objective@#To investigate the potential relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders (ASD), to provide a basis for the diagnosis and treatment of children with ASD.@*Methods@#A total of 40 ASD children who were treated or recovered in Xi an medical institutions and 16 typically developing (TD) children who were from several kindergatens in Xi an were invited for participation. Sensory characteristics were evaluated by the sensory processing and self regulation checklist, 3D structural brain images were obtained with TIWI, and gray matter volumes were analyzed by voxel based morphometry. Sensory characteristics and gray matter volumes were compared between groups and the relationship between sensory characteristics and different gray matter volumes were analyzed.@*Results@#The scores of auditory, visual, tactile, sensory processing ability and sensory under responsivity in the ASD group were lower than those in the TD group ( Z/t =-2.63, -2.57 , -3.11, -2.19, -3.83, P <0.05). Gray matter volumes in nine brain regions increased in the ASD group compared to the TD group, including the left and right posterior inferior lobe, right parahippocamal gyrus, left insula, left media frontal gyrus, left superion occipital gyrus, right superion occipital gyrus, right superion parietal lobe, and right posterion central gyrus ( t =3.53, 3.69 , 3.37, 3.86, 3.61, 3.37, 4.04, 3.38, 3.16, P <0.01). In the ASD group, the scores of visual, vestibular, proprioceptive, sensory processing ability, sensory seeking behavior and sensory over responsivity were negatively correlated with gray matter volumes of left superior occipital gyrus ( r =-0.36, -0.40, -0.39, -0.36, -0.40, -0.36), and the scores of visual, vestibular, and sensory over responsivity were negatively correlated with gray matter volumes of the right superior parietal lobule ( r =-0.36, -0.50, -0.42)( P <0.05).@*Conclusion@#The presence of paresthesia in children with ASD is associated with gray matter volumes of the left superior occipital gyrus and right superior parietal lobule.

Retrospective analysis of strabismus surgery in adolescents and children in Yunnan province / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the strabismus surgery situation of adolescents and children in Yunnan province.METHODS: A retrospective analysis was conducted on medical records data of 3 068 adolescents and children who received strabismus surgery at Affiliated Hospital of Yunnan University from January 2017 to December 2021. The analysis included gender, constituent ratio of age, distribution of strabismus types and combination with other ocular diseases, etc.RESULTS: Among the included patients, 52.12% were males, and 47.88% were females. Preschool patients(1 to 6 years old)accounted for 32.89%, primary pupils(7 to 12 years old)accounted for 45.89% and high school students(13 to 18 years old)accounted for 21.22%. Exotropia accounted for 63.17% of the total strabismus, of which intermittent exotropia was the most common type. Esotropia accounted for 19.69%, and concomitant esotropia was the most common type. The special type of strabismus accounted for 17.14%, and A-V syndrome and dissociative vertical deviation(DVD)were the most common types. Strabismus combined with ametropia accounted for 61.02% and amblyopia accounted for 10.89%. A few patients also combined with other eye diseases.CONCLUSION: In Yunnan province, intermittent exotropia was the most common type of strabismus among adolescents and children. Some patients combined with other ocular diseases.

Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism / 中西医结合学报

OBJECTIVE@#Anxiety is one of the most common symptoms associated with autistic spectrum disorder. The essential oil of Cananga odorata (Lam.) Hook. f. & Thomson, usually known as ylang-ylang oil (YYO), is often used in aromatherapy as a mood-regulating agent, sedative, or hypotensive agent. In the present study, the effects and mechanisms of YYO in alleviating anxiety, social and cognitive behaviors in autism-like rats were investigated.@*METHODS@#The prenatal valproic acid (VPA) model was used to induce autism-like behaviors in offspring rats. The effectiveness of prenatal sodium valproate treatment (600 mg/kg) on offspring was shown by postnatal growth observation, and negative geotaxis, olfactory discrimination and Morris water maze (MWM) tests. Then three treatment groups were formed with varying exposure to atomized YYO to explore the effects of YYO on the anxiety, social and cognitive behaviors of the autistic-like offspring through the elevated plus-maze test, three-chamber social test, and MWM test. Finally, the monoamine neurotransmitters, including serotonin, dopamine and their metabolites, in the hippocampus and prefrontal cortex (PFC) of the rats were measured using a high-performance liquid chromatography.@*RESULTS@#Offspring of VPA exposure rats showed autism-like behaviors. In the VPA offspring, medium-dose YYO exposure significantly elevated the time and entries into the open arms in the elevated plus-maze test, while low-dose YYO exposure significantly enhanced the social interaction time with the stranger rat in session 1 of the three-chamber social test. VPA offspring treated with YYO exposure used less time to reach the platform in the navigation test of the MWM test. YYO exposure significantly elevated the metabolism of serotonin and dopamine in the PFC of VPA offspring.@*CONCLUSION@#YYO exposure showed the effects in alleviating anxiety and improving cognitive and social abilities in the offspring of VPA exposure rats. The role of YYO was related to the regulation of the metabolism of serotonin and dopamine. Please cite this article as: Zhang N, Wang ST, Yao L. Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism. J Integr Med. 2023; 21(2): 205-214.

The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse / 神经科学通报·英文版

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.

Change in corneal endothelial cell density and morphology in different stages of keratoconus / 中华实验眼科杂志

Objective:To assess the changes in corneal endothelial cell density (CD) and morphology in patients with different stages of keratoconus.Methods:A cross-sectional study was conducted.One hundred and nineteen patients (199 eyes) with keratoconus who were treated in the Eye Hospital of Shandong First Medical University were included from March 2018 to October 2021.The 199 eyes were classified into stage Ⅰ (111 eyes of 58 cases), stage Ⅱ (41 eyes of 30 cases), stage Ⅲ (47 eyes of 31 cases) keratoconus groups according to the Amsler-Krumeich classification.In the same period, 25 age- and sex-matched healthy subjects (50 eyes) were enrolled as a normal control group.Corneal topography and anterior segment parameters such as keratometry (K), central corneal thickness (CCT), thinnest corneal thickness (TCT), anterior chamber depth (ACD), corneal diameter and corneal volume were obtained by Pentacam 3-dimensional anterior segment imaging and analysis system.The corneal endothelial CD, percentage of hexagonal cells (6A), average cell area (AVE), maximum cell area (MAX), minimum cell area (MIN), cell area standard deviation (SD) and cell area coefficient of variation (CV) in the central area were evaluated by non-contact specular microscopy.The correlation between corneal endothelial CD, morphological parameters and corneal topographic parameters was analyzed by Spearman rank correlation.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Shandong Eye Hospital (No.SDSYKYY201803). All patients were informed of the purpose and methods of the study and written informed consent was obtained before any medical examination.Results:The CD of the normal control group and stage Ⅰ, Ⅱ, Ⅲ keratoconus groups was 2 941(2 809, 3 072), 2 825(2 667, 3 030), 2 747(2 475, 2 903) and 2 370(2 142, 2 525) cells/mm 2, respectively.With the progression of keratoconus, CD decreased gradually, and there was a significant difference in CD among the four groups ( H=94.862, P<0.001). There were significant differences in CV and 6A among the four groups ( H=45.018, 20.421; both at P<0.001). CV was significantly higher in stage Ⅲ keratoconus group than that of the normal control group and stage Ⅰ and Ⅱ keratoconus groups and 6A was significantly lower in stage Ⅲ keratoconus group than that of the normal control group and stage Ⅰ keratoconus group (all at P<0.05). With the progression of keratoconus, MAX, MIN, AVE and SD increased gradually, and there were significant differences in MAX, MIN, AVE and SD among the four groups ( H=37.905, 32.437, 110.182, 72.941; all at P<0.001). MAX and MIN in stage Ⅲ keratoconus group were significantly higher than those in stage Ⅰ keratoconus groups and normal control group (all at P<0.05). AVE and SD in stage Ⅲ keratoconus group were significantly higher than those in normal control group and stage Ⅰ and Ⅱ keratoconus groups (all at P<0.05). In patients with keratoconus, CD was moderately positively correlated with CCT ( rs=0.47, P<0.001) and TCT ( rs=0.53, P<0.001), and was moderately negatively correlated with mean keratometry (Km) ( rs=-0.59, P<0.001).6A was weakly positively correlated with CCT ( rs=0.18, P=0.01) and TCT ( rs=0.22, P=0.002), and was weakly negatively correlated with Km ( rs=-0.32, P<0.001). CV was weakly negatively correlated with CCT ( rs=-0.35, P<0.001) and TCT ( rs=-0.37, P<0.001), and was moderately positively correlated with Km ( rs=0.48, P<0.001). There was no correlation between CD, CV, 6A and ACD, or corneal volume. Conclusions:As the keratoconus progresses, the cornea protrudes and becomes thinner with CD and 6A decreasing while CV increasing.Corneal topographic parameters are related to the density and morphology of corneal endothelial cells.

Research progress on the influencing factors of health literacy in patients with coronary heart disease based on the perspective of health ecology / 中国实用护理杂志

The self-health management level of patients with coronary heart disease depends largely on their health literacy level. The theory of health ecology believes that the factors affecting individual health are multi-level. Based on the perspective of health ecology, this paper analyzed the influencing factors of health literacy of patients with coronary heart disease from five aspects: personal characteristics, behavior, interpersonal network, living and working conditions, environmental policies, so as to provide a basis for formulating targeted and systematic strategies for improving the health literacy of patients with coronary heart disease in the future.

Urban-rural differentials in the relationship between personality traits and changes in depressive symptoms / 北京大学学报(医学版)

OBJECTIVE@#The prevalence of depressive symptoms has become a significant public health issue in China. Research on the relationship between personality traits and changes in depressive symptoms, as well as further exploration of urban-rural differences, not only benefits for the understanding of the prevalence trend of depression in China, but also provides a useful reference for the government to develop personalized mental health prevention strategies.@*METHODS@#Based on the data from the China Family Panel Studies in 2018 and 2020, a univariate analysis was conducted on 16 198 Chinese residents aged 18 years and above. Five dimensions of personality traits were conscientiousness, extraversion, agreeableness, neuroticism and openness. In the study, 16 198 residents were divided into "keep good group", "better group", "worse group" and "keep bad group" according to the changes in depressive symptoms in 2018 and 2020. After controlling for factors, such as gender and education, multinomial Logistic regression analysis was used to examine whether personality traits were associated with changes in depressive symptoms. In addition, we evaluated whether urban-rural and personality traits interacted to influence depressive symptoms.@*RESULTS@#The five dimensions of personality traits were significantly correlated with changes in depressive symptoms. Conscientiousness, extroversion, and agreeableness were negatively associated with depressive symptoms, while neuroticism and openness were positively related. Urban and rural differences moderated the relationship between personality traits and depressive symptoms. Compared with urban residents, rural residents showed stronger correlations between neuroticism (OR=1.14; 95%CI: 1.00-1.30) and the group of depression-recovery, as well as conscientiousness (OR=0.79;95%CI: 0.68-0.93) and the group of persistent-depression.@*CONCLUSION@#The study finds that personality traits have a significant correlation with changes in depressive symptoms, with certain traits showing a negative or positive relationship. Specifically, higher levels of conscientiousness, extraversion, and agreeableness are associated with lower levels of depressive symptoms, while higher levels of neuroticism and openness are associated with higher levels of depressive symptoms. In addition, the study finds that rural residents have a stronger association between their personality traits and persistent or improved depressive symptoms, which highlights the need for tailoring mental health intervention and prevention programs that should take into account personality traits and urban-rural differences in China. By developing targeted strategies that are sensitive to personality differences and geographic disparities, policymakers and mental health professionals can help prevent and reduce the incidence of depressive symptoms, ultimately improving the overall well-being of Chinese adults. Meanwhile, additional studies in independent populations are needed to corroborate the findings of this study.

Expert consensus on late stage of critical care management / 中华内科杂志

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.

The predictive value of warning scores for intensive care unit admission in coronavirus disease 2019 patients / 中华内科杂志

To evaluate the predictive value of early warning scores for intensive care unit (ICU) admission in patients with coronavirus disease 2019 (COVID-19). For COVID-19 patients who were admitted to Shijiazhuang People's Hospital from January 2021 to February 2021, national early warning score (NEWS), national early warning score 2 (NEWS2), rapid emergency medicine score (REMS), quick sepsis-related organ failure (qSOFA), altered consciousness, blood urea nitrogen, respiratory rate, blood pressure, and age-65 (CURB-65) were used to evaluate the inpatient condition and the predictive value for ICU admission. A total of 368 patients were included, and 32 patients (8.7%) were transferred to the ICU. The median age was 49.0 (34.0,61.0) years. The scores of NEWS, NEWS2, REMS, and CURB-65 were 1 (0, 2), 1 (0, 2), 4 (2, 6) and 0 (0, 1), respectively. The receiver operating characteristic (ROC) cure (AUC) was used to evaluate the predictive value in detecting patients who are at risk of being transferred to the ICU. Area under the ROC AUC of NEWS was 0.756, sensitivity 65.6%, and specificity 71.3%. ROC AUC of NEWS2 was 0.732, sensitivity 62.5%, and specificity 61.3%. ROC AUC of REMS was 0.787, sensitivity 84.4%, and specificity 64.6%. ROC AUC of CURB-65 was 0.814, sensitivity 81.3%, and specificity 76.8%. The predictive value of NEWS and NEWS2 combined with age were significantly improved. The ROC AUC of NEWS combined with age was 0.885, sensitivity 85.1%, and specificity 75.0%. The ROC AUC of NEWS2 combined with age was 0.883, sensitivity 84.2%, and specificity 75.0%. NEWS and NEWS2 combined with age can be used as a predictive tool for whether COVID-19 patients will be admitted to the ICU.

Application of mixture analysis methods in association between metals mixture exposure and DNA oxidative damage / 中华预防医学杂志

Objectives: To study the association between metals mixture exposure and DNA oxidative damage using mixture analysis methods, and to explore the most significant exposure factors that cause DNA oxidative damage. Methods: Workers from steel enterprises were recruited in Shandong Province. Urinary metals were measured by using the inductively coupled plasma mass spectrometry method. The level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined by using the ultra-high performance liquid chromatography-mass spectrometry method. Bayesian kernel machine regression (BKMR), elastic net regression and quantile g-computation regression were used to analyze the association between urinary metals and urinary 8-OHdG. Results: A total of 768 subjects aged (36.15±7.40) years old were included in the study. BKMR, elastic net regression and quantile g-computation all revealed an overall positive association between the mixture concentration and increased urinary 8-OHdG. The quantile g-computation results showed that with a 25% increase in metal mixtures, the urinary 8-OHdG level increased by 77.60%. The elastic net regression showed that with a 25% increase in exposure risk score, the urinary 8-OHdG level increased by 26%. The BKMR summarized the contribution of individual exposures to the response, and selenium, zinc, and nickel were significant contributors to the urinary 8-OHdG elevation. Conclusion: Exposure to mixed metals causes elevated levels of DNA oxidative damage, and selenium, zinc, and nickel are significant exposure factors.

Echinacoside hampers malignant progression of breast cancer MCF-7 cells by modulating AKR1B10/ERK signal transduction / 中国中药杂志

This study analyzes the impact of echinacoside(ECH) in the proliferation, metastasis and adriamycin(ADR) resistance of breast cancer(BC) MCF-7 cells via the modulation of aldo-keto reductase family 1 member 10(AKR1B10)/extracellular signal-regulated kinase(ERK) pathway. The chemical structure of ECH was firstly confirmed. MCF-7 cells were treated with different concentration(0, 10, 20, 40 μg·mL~(-1)) of ECH for 48 h. Western blot was used to analyze expression of AKR1B10/ERK pathway-associated proteins and cell counting kit-8(CCK-8) assay to determine cell viability. MCF-7 cells were collected and classified into control group, ECH group, ECH + Ov-NC group, and ECH + Ov-AKR1B10 group. Then Western blot was employed to analyze the expression of AKR1B10/ERK pathway-associated proteins. CCK-8 and 5-ethynyl-2'-deoxyuridine(EdU) assay were used to examine cell proliferation. Cell migration was appraised with scratch assay, Transwell assay, and Western blot. Eventually, MCF-7 cells were treated with ADR for 48 h to induce ADR resistance. Cell viability was tested by CCK-8 assay and cell apoptosis was estimated based on terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) assay and Western blot. Based on Protein Data Bank(PDB) and molecular docking, the binding affinity of ECH to AKR1B10 was assessed. Various doses of ECH decreased the expression of AKR1B10/ERK pathway-associated proteins in a dose-dependent manner and declined cell viability compared with the control group. Compared with the control group, 40 μg·mL~(-1) ECH blocked the AKR1B10/ERK pathway in MCF-7 cells and inhibited the proliferation, metastasis and ADR resistance of the cells. Compared with the ECH + Ov-NC group, ECH + Ov-AKR1B10 group showed the recovery of some biological behaviors of MCF-7 cells. ECH also targeted AKR1B10. ECH can inhibit the proliferation, metastasis, and ADR resistance of BC cells by blocking AKR1B10/ERK pathway.

Standardized Jin's three-needle therapy for stroke: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of standardized Jin's three-needle therapy on limb motor function and nerve function defect in stroke patients, and to evaluate the placebo control method.@*METHODS@#A total of 66 patients with stroke were randomly divided into a Jin's three-needle group (33 cases, 3 cases dropped off) and a placebo needle group (33 cases, 4 cases dropped off). All the patients were treated with conventional medication and rehabilitation treatment. In addition, the patients in the Jin's three-needle group were treated with standardized Jin's three-needle therapy at temporal three points, spirit four points, hand three points, foot three points, upper extremity spasm three points, lower extremity spasm three points, etc.; while the patients in the placebo needle group were treated with placebo needling at identical points. All the treatments were given once a day, 5 days a week, and 3-week treatment was given with an interval of 2 days between weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were observed before treatment, 10 d and 21 d into treatment, and the blind evaluation was conducted after treatment.@*RESULTS@#On the 10 d and 21 d into treatment, the FMA scores in both groups were higher than those before treatment (P<0.01), and the NIHSS scores were lower than those before treatment (P<0.01). On the 10 d and 21 d into treatment, the FMA scores in the Jin's three-needle group were higher than those in the placebo needle group (P<0.05); on the 10 d into treatment, the NIHSS score in the Jin's three-needle group was were lower than that in the placebo needle group (P<0.05). There was no significant difference between the two groups on judging the type of treatment (P>0.05), and the consistency with the real situation was poor (Cohen's kappa coefficient<0.20).@*CONCLUSION@#The standardized Jin's three-needle therapy could effectively improve the limb motor function and nerve function defect in stroke patients. The placebo control method used in this study shows good clinical operability and masking effect.

Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miRNAs / 中华肿瘤杂志

Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.

Chang Wei Qing Decoction enhances the anti-tumor effect of PD-1 inhibitor therapy by regulating the immune microenvironment and gut microbiota in colorectal cancer / 中国天然药物

The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment (TIME). This study aimed to mechanistically assess whether Chang Wei Qing (CWQ) Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy. PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), rather than those with mismatch repair-proficient/microsatellite stable (pMMR/MSS) CRC. Hence, immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients. Flow cytometry was used to analyze T-lymphocytes in tumors from mice. Western blot was used to measure the expression of PD-L1 protein in mouse tumors. The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry. 16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice. Subsequently, Spearmanapos;s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes. The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins. In vivo, CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+ and PD-1+CD8+ T cells in tumors. Additionally, the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone. CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes, andActinobacteria. Additionally, the proportion of infiltrated CD8+PD-1+, CD8+, and CD3+ T cells were found to be positively correlated with the abundance of Akkermansia. Accordingly, CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.