Study of Triptolide on Liver Injury and Detoxification Strategy / 中国实验方剂学杂志

As a commonly used traditional Chinese medicine in clinical practice， Tripterygium wilfordii has the functions of dispelling wind and removing dampness， detoxicating and destroying parasites， detumescence， pain relief， promoting blood circulation， and dredging collateral. Modern pharmacological studies show that it also has other functions such as anticancer， anti-inflammation， and immunosuppression. It has been widely used to treat autoimmune diseases， renal diseases， and tumors. T. wilfordii contains a variety of chemical components， among which triptolide （TP） can cause varying degrees of damage to human digestive， circulatory， reproductive， and other systems， with liver injury being the most common one， which greatly limits the development of TP in new drug research and industrial application. Therefore， the authors focused on the research hotspot of TP-induced liver injury and summarized relevant Chinese and international literature regarding the clinical manifestations， injury mechanisms， and detoxification strategies of TP-induced liver injury. This helps to provide a scientific basis for the clinical drug safety and scientific drug supervision of TP. The clinical manifestations of TP-induced liver injury are mostly abnormal transaminases， loss of appetite， nausea and vomiting， anorexia， yellow staining of skin and sclera， and yellow urine. The mechanisms of the above clinical manifestations involve apoptosis， oxidative stress， influence on cytochrome P450 superfamily， macrophage polarization， regulation of biological clock gene Clock， etc. Among them， cell apoptosis is related to neurogenic locus notch homolog protein 1 （Notch1）， dynamin-related protein 1 （Drp1）-cytochrome C （Cyt C）， phosphatidylinositide 3-kinases （PI3K）/protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， tumor suppressor protein 53 （p53）， Fas cell surface death receptor （Fas）/Caspase-8， and other signaling pathways. Oxidative stress is related to inhibition of nuclear factor-erythroid 2-related factor 2 （NRF2） signaling pathway， promotion of cytochrome P450 2E1 （CYP2E1） expression， and excessive accumulation of reactive oxygen （ROS）. The influence of the cytochrome P450 superfamily is manifested as reducing the substrate affinity， activity， and expression of cytochrome P450 3A （CYP3A）， cytochrome P450 2C9 （CYP2C9）， cytochrome P450 2C19 （CYP2C19）， and cytochrome P450 1A2 （CYP1A2）. Promoting the transformation of macrophages into the M1 type is related to the secretion of inflammatory factors and the accumulation of endotoxin， and the internal rhythmic regulation of the biological clock gene Clock， is related to the expression of cytochrome P450 3A11 （CYP3A11） metabolic enzyme. The detoxification strategies in the clinical application include herbs-processing detoxification strategy and drug-pairing detoxification. The traditional Chinese medicines and monomers that are helpful for detoxification include Glycyrrhiza uralensis， Paeonia lactiflora， Lysimachia christinae， Rehmannia glutinosa， saffron， and paeoniflorin. The reviews and discussion about these topics can help to provide more references for related research and clinical application of TP.

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.

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.

Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis / 中国中药杂志

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

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.

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.

Value of machine learning model based on 18F-FDG PET/CT radiomics features in differential diagnosis between gastric cancer and primary gastric lymphoma / 中华核医学与分子影像杂志

Objective:To investigate the value of machine learning model based on 18F-FDG PET/CT radiomics features in preoperative differential diagnosis of gastric cancer (GC) and primary gastric lymphoma (PGL). Methods:A total of 155 patients with GC (104 males, 51 females; age (59.3±12.8) years) and 82 patients with PGL (40 males, 42 females; age (56.8±14.6) years) who underwent 18F-FDG PET/CT imaging before treatment from January 2012 to December 2020 in Tianjin Medical University Cancer Institute and Hospital were included in this retrospective study. Patients were randomly divided into training set and test set by using Python3.7.1 software. Volumes of interest (VOIs) in PET and CT images were drawn and two-dimensional and three-dimensional radiomics features were extracted. Two machine learning models, including multi-layer perceptron (MLP) and support vector machine (SVM), were established based on CT radiomics features alone, PET radiomics features alone and PET/CT radiomics features to differentiate GC and PGL, respectively. The predictive performance of each model was evaluated by ROC curve analysis. Results:There were 166 patients in training set and 71 patients in test set. Generally, SVM machine learning model based on PET/CT radiomics features showed a trend to be superior to MLP machine learning model in the differential diagnosis of GC and PGL (PET-SVM: AUC=0.88, 95% CI: 0.83-0.94); PET/CT-MLP: AUC=0.80, 95% CI: 0.73-0.87; z=1.15, P=0.337). The AUC of PET/CT-SVM machine learning model was significantly higher than that of CT-SVM machine learning model (CT-SVM: AUC=0.74, 95% CI: 0.67-0.81; z=2.28, P=0.022). Conclusion:Machine learning model based on 18F-FDG PET/CT radiomics features is expected to be a non-invasive, effective tool for preoperative differential diagnosis of GC and PGL.

Serum Anti-Fumarate Hydratase Autoantibody as a Biomarker for Predicting Prognosis of Acute-on-Chronic Liver Failure

Background/Aims@#To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). @*Methods@#An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. @*Results@#Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach.Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. @*Conclusions@#The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.

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.

Lipopolysaccharides protect mesenchymal stem cell against cardiac ischemia-reperfusion injury by HMGB1/STAT3 signaling / 老年心脏病学杂志（英文版）

BACKGROUND@#Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown.@*METHODS@#In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot.@*RESULTS@#The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC.@*CONCLUSIONS@#These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

Sjögren's syndrome combined with cold agglutinin disease: A case report / 北京大学学报(医学版)

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.

Self-Appraisal of Clinical Competence in Echocardiography of Chinese Intensivists Post Basic Echocardiography Training / 中国医学科学杂志(英文版)

Objectives To learn the echocardiography skills of intensivists after receiving a basic critical care echocardiography training course, and investigate factors that may influence their performance. Methods We completed a web-based questionnaire that assessed the skills in ultrasound scanning techniques of intensivists who took a training course on basic critical care echocardiography held in 2019 and 2020. Mann-Whitney test was used to analyze the factors which might affect their performance on image acquisition, recognizing clinical syndrome, and measuring the diameter of inferior vena cava, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral.Results We enrolled 554 physicians from 412 intensive care units across China. Among them, 185 (33.4%) reported that they had 10%-30% chance of being misled by critical care echocardiography when making therapeutic decision, and 34 (6.1%) reported that the chance was greater than 30%. Intensivists who performed echocardiography under the guidance of a mentor and finished ultrasound scanning more than 10 times per week reported significant higher scores in image acquisition, clinical syndrome recognition, and quantitative measurement of inferior vena cava diameter, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral than those without mentor and performing echocardiography 10 times or less per week respectively (all P < 0.05).Conclusion The skills in diagnostic medical echocardiography of Chinese intensivists after a basic echocardiographic training course remain low, and further quality assurance training program is clearly warranted.

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.

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis / 中华医学杂志(英文版)

As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.

Analysis on Ethical Issues in Off-label Use of Antitumor Drugs / 中国医学伦理学

The phenomenon of off-label use of antitumor drugs in the treatment of malignant tumors is relatively common. Although it is conducive to the development of clinical medical practice, but it is still necessary to pay attention to ethical issues such as medication risks and inadequate implementation of informed consent. Therefore, to effectively avoid ethical risks and standardize the rational use of off-label antitumor drugs, this paper proposed that pharmacists should actively participate in the process of off-label use of antitumor drugs, improve the evidence level of evidence-based medicine, implement patients’ right to informed consent, and improve the hospital’s supervision system of off-label drug use, so as to ensure the reasonable and legal use of drugs by patients.