Far-Infrared Therapy Based on Graphene Ameliorates High-Fat Diet-Induced Anxiety-Like Behavior in Obese Mice via Alleviating Intestinal Barrier Damage and Neuroinflammation.

The consumption of a high-fat diet (HFD) has been implicated in the etiology of obesity and various neuropsychiatric disturbances, including anxiety and depression. Compelling evidence suggests that far-infrared ray (FIR) possesses beneficial effects on emotional disorders. However, the efficacy of FIR therapy in addressing HFD-induced anxiety and the underlying mechanisms remain to be elucidated. Here, we postulate that FIR emitted from a graphene-based therapeutic device may mitigate HFD-induced anxiety behaviors. The graphene-FIR modify the gut microbiota in HFD-mice, particularly by an enriched abundance of beneficial bacteria Clostridiaceae and Erysipelotrichaceae, coupled with a diminution of harmful bacteria Lachnospiraceae, Anaerovoracaceae, Holdemania and Marvinbryantia. Graphene-FIR also improved intestinal barrier function, as evidenced by the augmented expression of the tight junction protein occludin and G protein-coupled receptor 43 (GPR43). In serum level, we observed the decreased free fatty acids (FFA), lipopolysaccharides (LPS), diamine oxidase (DAO) and D-lactate, and increased the glucagon-like peptide-2 (GLP-2) levels in graphene-FIR mice. Simultaneously, inflammatory cytokines IL-6, IL-1ß, and TNF-α manifested a decrease subsequent to graphene-FIR treatment in both peripheral and central system. Notably, graphene-FIR inhibited over expression of astrocytes and microglia. We further noticed that the elevated the BDNF and decreased TLR4 and NF-κB expression in graphene-FIR group. Overall, our study reveals that graphene-FIR rescued HFD-induced anxiety via improving the intestine permeability and the integrity of blood-brain barrier, and reduced inflammatory response by down regulating TLR4/NF-κB inflammatory pathway.

Far-infrared therapy promotes exercise capacity and glucose metabolism in mice by modulating microbiota homeostasis and activating AMPK.

The benefits of physical exercise on human health make it desirable to identify new approaches that would mimic or potentiate the effects of exercise to treat metabolic diseases. However, whether far-infrared (FIR) hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regulation, and its underling mechanisms remain unclear. Here, a specific far-infrared (FIR) rays generated from graphene-based hyperthermia devices might promote exercise capacity and metabolisms. The material characterization showed that the graphene synthesized by chemical vapour deposition (CVD) was different from carbon fiber, with single-layer structure and high electrothermal transform efficiency. The emission spectra generated by graphene-FIR device would maximize matching those adsorbed by tissues. Graphene-FIR enhanced both core and epidermal temperatures, leading to increased blood flow in the femoral muscle and the abdominal region. The combination of microbiomic and metabolomic analysis revealed that graphene-FIR modulates the metabolism of the gut-muscle axis. This modulation was characterized by an increased abundance of short-chain fatty acids (SCFA)-producing bacteria and AMP, while lactic acid levels decreased. Furthermore, the principal routes involved in glucose metabolism, such as glycolysis and gluconeogenesis, were found to be altered. Graphene-FIR managed to stimulate AMPK activity by activating GPR43, thus enhancing muscle glucose uptake. Furthermore, a microbiota disorder model also demonstrated that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4. Our results provided convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis. These novel findings regarding the therapeutic effects of graphene-FIR suggested its potential utility as a mimetic agent in clinical management of metabolic disorders.

Influence of diet and exercise management combined health education mode on aged patients with chro-nic heart failure / 心血管康复医学杂志

Objective:To study influence of diet and exercise management combined health education mode on aged patients with chronic heart failure(CHF).Methods:A total of 124 aged CHF patients treated in our hospital were randomly and equally divided into routine nursing group and combined intervention group(received diet and exercise management combined health education mode intervention based on routine nursing group)according to random number table method.Both groups were intervened for two months.General clinical data,left ventricular end-sys-tolic dimension(LVESd),left ventricular end-diastolic dimension(LVEDd),LVEF,6min walking distance(6MWD)and scores of Minnesota living with heart failure questionnaire(MLHFQ)and before and after interven-tion were compared between two groups.Results:Compared with routine nursing group,after intervention,there were significant reductions in LVESd[(44.88±4.90)mm vs.(33.09±3.40)mm],LVEDd[(54.02±5.49)mm vs.(48.80±5.50)mm],scores of emotional[(17.44±4.55)scores vs.(7.89±4.54)scores],physical[(31.69 ±5.73)scores vs.(21.89±6.02)scores]and others[(32.12±4.22)scores vs.(13.00±2.84)scores]of MLH-FQ and total score[(81.25±9.28)scores vs.(42.77±8.05)scores],and significant rise in LVEF[(49.64± 4.81)％vs.(52.32±4.22)％],6MWD[(352.67±28.79)m vs.(449.38±23.82)m],scores of self-care main-tenance[(2.06±0.39)scores vs.(3.26±0.51)scores],self-care management[(6.21±1.07)scores vs.(9.65 ±1.18)scores]and self-care confidence[(1.06±0.26)scores vs.(3.12±0.56)scores]in combined interven-tion group(P=0.001 all).Conclusion:Diet and exercise management combined health education mode can signifi-cantly improve cardiac function,self-management ability and quality of life in aged patients with chronic heart failure.

The study on the effect of neuregulin-1 on myocardial injury in septic rats / 重庆医学

Objective To study the effect of neuromodulatory protein-1(NRG-1)in inhibiting sepsis induced myocardial injury and its mechanism.Methods The rat sepsis model was established by cecal ligation and puncture(CLP).SD rats were divided into the sham operation group,sepsis group,sepsis+NRG group(rhNRG,10 μg/kg).After 12,24 h of successful modeling,the heart and peripheral serum of the surviving rats in each group were taken respectively.The HE staining was used to observe the changes of cardiac tissue morphology and structure,and ELISA was used to detect the expression levels of creatine kinase(CK),crea-tine kinase MB isoenzyme(CK-MB),sensitive troponin Ⅰ(cTnⅠ)in serum,tumor necrosis factor-α(TNF-α)in cardiac tissue and IL-6 expression level;Western blot was used to detect the phosphorylation protein ki-nase B(p-Akt),phosphorylation glycogen synthase kinaseβ(p-GSK3β),B-cell lymphoma/leukemia-2(Bcl-2)and Bax protein expression in rat myocardial tissue.Results After 12,24 h of modeling,compared with the sham group,the expression levels of CK,CK-MB and cTnⅠ in serum,TNF-α,IL-6 and Bax protein in myocar-dial tissue in the sepsis group all were significantly increased(P＜0.05),while the expression levels of p-Akt and p-GSK3β in myocardial tissue were significantly decreased(P＜0.05).After 12,24 h of modeling,com-pared with the sepsis group,the expression levels of CK,CK-MB,cTn Ⅰ in the serum and the expression levels of TNF-α,IL-6 in the myocardial tissue of the sepsis+NRG group were significantly decreased;after 24 h of modeling,compared with the sepsis group,the expression level of Bax protein in myocardial tissue of the sep-sis+NRG group was decreased,while the p-Akt,p-GSK3β expression levels were increased(P＜0.05).The pathological results showed that compared with the sham operation group,the sepsis group produced signifi-cant lesions;compared with the sepsis group,the lesions in the sepsis+NRG group were alleviated.Conclusion The expression levels of related biomarkers in septic myocardial injury have change.NRG-1 could improve the cardiac function through Akt/GSK3β pathway,inhibit the related proinflammatory factors and reduce the myocardial tissue damage.

Effect of montelukast combined with budesonide in the treatment of children with intermittent asthma / 中国医师进修杂志

Objective:To analyze the effect of montelukast combined with budesonide in the treatment of children with intermittent asthma, and the impact on airway remodeling and T helper type 1 (Th1)/T helper type 2 (Th1/Th2) related cytokines.Methods:A prospective study was conducted among 120 children with intermittent asthma admitted to Huanghua Municipal People′s Hospital from December 2021 to February 2023. The children were randomly divided into the control group (60 children treated with budesonide atomizationinhalation) and the observation group (60 children treated with montelukast on the basis of the treatment of control group). Clinical efficacy, airway remodeling indicators [total area of airway (Ao), outer diameter of airway (D) and wall area to total airway cross-sectional area (WA%)], pulmonary function [peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV 1)/forced vital capacity (FVC) and the maximum expiratory flow at 25% of vital capacity (MEF25%)], Th1/Th2 related cytokines, inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6) and interferon-gamma (IFN-γ)], recurrence, and the incidence of adverse reactions were compared between the two groups. Results:The total effective rate in the observation group was higher than that in the control group: 90.00% (54/60) vs. 75.00% (45/60) ( P<0.05). After treatment, Ao, D and WA% in the observation group were lower than those in the control group: (17.58 ± 1.89) mm 2 vs. (19.22 ± 1.94) mm 2, (4.25 ± 0.48) mm vs. (4.48 ± 0.49) mm, (63.75 ± 6.49)% vs. (69.22 ± 7.14)% ( P<0.05). PEF, FEV 1/FVC and MEF25% in the observation group were higher than those in the control group: (3.13 ± 0.34) L/s vs. (2.86 ± 0.35) L/s, (87.45 ± 8.86) % vs. (83.59 ± 8.42) %, (87.63 ± 8.86)% vs. (82.15 ± 8.43)% ( P<0.05). The levels of Th1 and Th1/Th2 in the observation group were higher than those in the control group: (14.13 ± 1.46) % vs. (10.27 ± 1.25) %, 3.46 ± 0.39 vs. 1.88 ± 0.25, and the level of Th2 was lower than that in the control group: (3.96 ± 0.45)% vs. (5.48 ± 0.56)% ( P<0.05). After treatment, the levels of TNF-α and IFN-γ in the observation group were higher than those in the control group: (76.15 ± 7.78) ng/L vs. (66.38 ± 6.47) ng/L, (7.15 ± 0.74) ng/L vs. (6.14 ± 0.66) ng/L. The levels of IL-4 and IL-6 were lower than those in the control group: (77.85 ± 7.96) ng/L vs. (86.42 ± 8.74) ng/L, (37.25 ± 3.89) mg/L vs. (44.23 ± 4.57) mg/L ( P<0.05). The recurrence rate in the observation group was lower than that in the control group: 3.33% (2/60) vs. 15.00% (9/60) ( P<0.05). The incidence rates of adverse reactions in the two groups were without statistically significant difference between the groups ( P>0.05). Conclusions:Montelukast combined with budesonide can reduce airway remodeling in children with intermittent asthma, improve their pulmonary function, Th1/Th2 related cytokines and inflammatory response indicators, and reduce recurrence rate, with good safety.

Exploration on Syndrome Differentiation Thinking for Stress Sensitization-induced Depression from the Perspective of"Deficient Qi with Stagnation and Heat" / 中国中医药信息杂志

TCM proposes that the core pathological mechanism of depression is"deficient qi with stagnation and heat",with the following pathogenic characteristics and evolution patterns:"deficient qi"as the nature,and deficiency in nature is in spleen,and deficiency in superficiality is in brain;"stagnation"is the superficiality,and qi stagnation,phlegm stagnation,and blood stagnation are in the brain collaterals;"heat"fires the brain collaterals,depression raised the heat,and excessive heat accumulated to stagnation.Based on the understanding of the pathogenesis of depression caused by stress sensitization in modern medicine,this article explored the potential association between this mechanism and the core pathogenesis of"deficient qi with stagnation and heat".It proposed that tonifying deficiency,promoting circulation,and clearing heat are the basic treatment principles for depression.By inhibiting inflammatory reactions and improving the stress sensitization state of neurons and glial cells,TCM compound formulas can exert multi-target and multi-dimensional therapeutic characteristics.

Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength.@*METHODS@#We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.@*RESULTS@#In the multimetal linear regression, Cu (β = -2.119), As (β = -1.318), Sr (β = -2.480), Ba (β = 0.781), Fe (β = 1.130) and Mn (β = -0.404) were significantly correlated with grip strength ( P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95% confidence interval: -1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn ( P interactions of 0.003 and 0.018, respectively).@*CONCLUSION@#In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Effects of vascular endothelial growth factor inhibitor SU5416 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension / 中国新生儿科杂志

Objective:To study the effects of vascular endothelial growth factor (VEGF) inhibitor SU5416 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).Methods:Thirty-two neonatal rats (age 7~10 d) were randomly assigned into normoxia group, hypoxia group, SU5416+hypoxia group and SU5416+normoxia group according to corresponding treatments. The endpoint was 14 d after treatments. Right ventricular systolic pressure (RVSP) was measured and cardiac and pulmonary tissue were sampled on the day. Right ventricular hypertrophy index (RVHI) was calculated. After HE staining, the morphological changes of pulmonary vessels were observed under light microscope.Media thickness (MT), external diameter(ED), cross-sectional area of tunica media (MA) and total cross-sectional area(TA) of pulmonary arterioles were measured. MT%(MT/ED) and MA%(MA/TA) were calculated as indicators of pulmonary vascular remodeling. The levels of VEGF and α-smooth muscle actin (α-SMA) in pulmonary vessels were examined using immunohistochemistry (IHC) method.Results:RVSP, RVHI, MT% and MA% in hypoxia group and SU5416+hypoxia group were significantly higher than normoxia group and SU5416+normoxia group ( P<0.05). These indicators in SU5416+hypoxia group were also higher than hypoxia group ( P<0.05),and no significant differences existed between SU5416+normoxia group and normoxia group ( P>0.05). The levels of α-SMA and VEGF in pulmonary vessels in SU5416+hypoxia group and hypoxia group were significantly higher than normoxia group and SU5416+normoxia group ( P<0.05), and α-SMA and VEGF in SU5416+hypoxia group higher than hypoxia group ( P<0.05). Conclusions:VEGF inhibitor SU5416 may exacerbate pulmonary hypertension and increase pulmonary vascular remodeling in neonatal HPH rats.

Discussion on application of mean gamma index to Compass 3D dose verification in target area receiving 50% of prescribed dose / 中华放射医学与防护杂志

Objective:To explore the value of using the mean gamma index (GI) in targer area receiving 50% prescribed dose as reference in VMAT planned dose verification through model-based dose calculation and measurement-based dose reconstruction.Methods:Based on Compass dose verificantion system, the VMAT plans for 70 patients were validated using two method. The mean GI and passing rate in target area receiving 50% of prescribed dose area for each validation plan were obtained to evaluate its application value in dose validation. First, plan information obtained by TPS calculation was input into the Compass system for performing independent dose calculation based on the accelerator data model, and obtain a three-dimensional dose based on the independent model calculation. The planned fluence measured for each patient′s treatment plan on the accelerator was reconstructed through the Compass system to obtain a three-dimensional dose based on measurement reconstruction. The three-dimensional dose obtained by the two method were compared with the three-dimensional dose calculated by TPS.Results:Combined with the gamma criteria of 3%/3 mm in the error setting condition of GI analysis, the mean GI in the area receiving 50% of prescribed dose was evaluated. GI≤0.4 was classified as PASS, 0.4 < GI ≤ 0.6 as being clinically acceptable, and GI > 0.6 as FAIL. The VMAT planned dose verification for 70 patients showed that the model-based independent calculation was in a better agreement with the TPS calculation. The GI values were all < 0.6: GI≤0.4 for 67 patients and 0.4 <GI≤ 0.6 for the other 3 patients, with gamma passing rate larger than 92%. The in- vivo measurement-based reconstructed 3D dose are slightly lesser than the model-based planed result ; theGI values were all < 0.6: GI ≤0.4 for 35 patients and 0.4 < GI ≤ 0.6 for other 35 patients, with gamma pass rate larger than 88%, of which gamma passing rate > 90% for 88 patients and < 90% for other 2, all meeting the requirements of clinical dose verification. The model-based independent dose verification is better than the measurement-based reconstructed dose verificantion, and the difference is statistically significant ( t=15.20, 10.71, P < 0.05). Conclusions:The mean GI in target area receiving 50% of prescribed dose can be used as a reference to judge the operatability of clinical plan in clinical dose verification. The mean GI value, in combination with the comprehensive result of gamma passing rate, is more convincing to evaluate dose verification. A combination of model-based dose verification, despite time-saving and labor-saving, and the measurement-based dose verification could become a reliable dose verification method for clinical application.

Xuebijing injection inhibits the degradation of pulmonary vascular endothelial calyx to improve acute lung injury induced by severe heatstroke / 解放军医学杂志

Objective To investigate the possible mechanism of Xuebijing injection in regulating abnormal degradation of pulmonary vascular endothelial calyx to improve acute lung injury induced by severe heatstroke.Methods Forty-eight Wistar rats were randomly divided into control group,heatstroke group and Xuebijing group.Before heatstroke induction,rats in Xuebijing group were administrated with Xuebijing injection(2 ml/kg,2 times/d)for 3 days.All rats were exposed to an environment with temperature of(40±2)℃and humidity of 65%±5%for 60 minutes to induce heatstroke.Two hours later,the lung wet/dry weight ratio was recorded;the concentration of proteins in BALF was measured;the pulmonary vascular permeability was measured by Evans blue(EB);HE staining was used to observe the pathological changes of lung tissue;the changes of hyaluronic acid(HA)on the surface of pulmonary vessels were observed by immunofluorescence;Western blotting was used to detect the expression of Syndecan-1,Glypican-1,VE-Cadherin,Occludin,VCAM-1 and E-selectin in lung tissues;Enzyme-linked immunosorbent assay(ELISA)was utilized to quantify the concentration of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)in serum and heparanase(HPA)in lung tissue.Results Xuebijing could decrease the lung wet/dry weight ratio,reduce protein exudation and improve pulmonary vascular permeability(P<0.01);reduce the histological injury(P<0.01);reduce the degradation of HA,Syndecan-1 and Glypican-1 on the surface of pulmonary vessels(P<0.01);increase the expression of VE-Cadherin and Occludin(P<0.01);regulate the overexpression of VCAM-1 and E-selectin(P<0.01);down-regulate the expression of TNF-α,IL-6 and HPA(P<0.01).Conclusion Xuebijing injection decrease the expression of HPA,improve the disintegration of pulmonary vascular endothelial calyx,repair the integrity of pulmonary vessels,reduce the damage of cell connections,down-regulate the expression of adhesion molecules,inhibit the inflammatory reaction,relieving acute lung injury caused by severe heat stroke.

Application of typical tasks-based mind mapping in nursing teaching for children with autism spectrum disorder / 中华医学教育探索杂志

Objective:To explore the application of typical tasks-based mind mapping in nursing teaching for children with autism spectrum disorder (ASD).Methods:A total of 102 nursing students who were involved in the nursing of children with ASD in Hunan Children's Hospital were selected and divided into control group and observation group according to the teaching methods. Fifty-one students in the control group were provided with conventional teaching, while 51 students in the observation group were provided with typical tasks-based mind mapping teaching. The students in the two groups were assessed for performance, self-directed learning ability score, and overall literacy at completion of the nursing course. SPSS 22.0 was used for the t test. Results:The scores of theoretical examination[(92.34±4.07) vs. (89.92±3.61)], nursing note writing[(91.07±3.84) vs. (88.60±3.59)], and operational examination[(90.47±2.98) vs. (88.52±2.73)] were significantly higher among students in the observation group than among those in the control group ( P<0.05); after the internship, students in the two groups had significantly increased scores in interpersonal relationships, learning awareness, learning strategies, learning behaviors, and learning evaluation, and the observation group had better performance than the control group in the above indices ( P<0.05); after the internship, students in the two groups had significantly increased scores in problem solving, interpersonal communication, critical thinking, and self-leadership, and the observation group had better performance than the control group in the above indices ( P<0.05). Conclusion:The application of typical tasks-based mind mapping in nursing teaching for children with ASD can improve nursing students' academic performance, enhance their self-directed learning, and improve their overall literacy.

Treadmill exercise alleviates neuropathic pain by regulating mitophagy of the anterior cingulate cortex in rats / 生理学报

This study aimed to investigate the effect of treadmill exercise on neuropathic pain and to determine whether mitophagy of the anterior cingulate cortex (ACC) contributes to exercise-mediated amelioration of neuropathic pain. Chronic constriction injury of the sciatic nerve (CCI) was used to establish a neuropathic pain model in Sprague-Dawley (SD) rats. Von-Frey filaments were used to assess the mechanical paw withdrawal threshold (PWT), and a thermal radiation meter was used to assess the thermal paw withdrawal latency (PWL) in rats. qPCR was used to evaluate the mRNA levels of Pink1, Parkin, Fundc1, and Bnip3. Western blot was used to evaluate the protein levels of PINK1 and PARKIN. To determine the impact of the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) on pain behaviors in CCI rats, 24 SD rats were randomly divided into CCI drug control group (CCI+Veh group), CCI+CCCP low-dose group (CCI+CCCP0.25), CCI+CCCP medium-dose group (CCI+CCCP2.5), and CCI+CCCP high-dose group (CCI+CCCP5). Pain behaviors were assessed on 0, 1, 3, 5, and 7 days after modeling. To explore whether exercise regulates pain through mitophagy, 24 SD rats were divided into sham, CCI, and CCI+Exercise (CCI+Exe) groups. The rats in the CCI+Exe group underwent 4-week low-moderate treadmill training one week after modeling. The mechanical pain and thermal pain behaviors of the rats in each group were assessed on 0, 7, 14, 21, and 35 days after modeling. Western blot was used to detect the levels of the mitophagy-related proteins PINK1, PARKIN, LC3 II/LC3 I, and P62 in ACC tissues. Transmission electron microscopy was used to observe the ultrastructure of mitochondrial morphology in the ACC. The results showed that: (1) Compared with the sham group, the pain thresholds of the ipsilateral side of the CCI group decreased significantly (P < 0.001). Meanwhile, the mRNA and protein levels of Pink1 were significantly higher, and those of Parkin were lower in the CCI group (P < 0.05). (2) Compared with the CCI+Veh group, each CCCP-dose group showed higher mechanical and thermal pain thresholds, and the levels of PINK1 and LC3 II/LC3 I were elevated significantly (P < 0.05, P < 0.01). (3) The pain thresholds of the CCI+Exe group increased significantly compared with those of the CCI group after treadmill intervention (P < 0.001, P < 0.01). Compared with the CCI group, the protein levels of PINK1 and P62 were decreased (P < 0.001, P < 0.01), and the protein levels of PARKIN and LC3 II/LC3 I were increased in the CCI+Exe group (P < 0.01, P < 0.05). Rod-shaped mitochondria were observed in the ACC of CCI+Exe group, and there were little mitochondrial fragmentation, swelling, or vacuoles. The results suggest that the mitochondrial PINK1/PARKIN autophagy pathway is blocked in the ACC of neuropathic pain model rats. Treadmill exercise could restore mitochondrial homeostasis and relieve neuropathic pain via the PINK1/PARKIN pathway.

Drug resistance and genomic characteristics of Salmonella enterica serovar London from clinical and food sources in Hangzhou City from 2017 to 2021 / 中华预防医学杂志

Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.

Solid Tumors With Cold Agglutinins:Report of Two Cases and Literature Review / 中国医学科学院学报

Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome.@*METHODS@#In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded.@*RESULTS@#From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05).@*CONCLUSION@#Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).

Ferroptosis in laryngeal squamous cell carcinoma and its regulation by M2 macrophage-derived exosomes / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04±0.65 vs. 0.99±0.09, F=30.36, P<0.001), and was closely related to T stage and clinical stage (Ⅰ-Ⅱvs.Ⅲ-Ⅳ: 1.75±0.39 vs. 2.18±0.71, F=2.25, P<0.05; T1-2 vs. T3-4: 1.71±0.42 vs. 2.20±0.69, F=2.06, P<0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P<0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells.

Effect and mechanism of vascular endothelial growth factor-A on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension / 中国当代儿科杂志

OBJECTIVE@#To study the role of vascular endothelial growth factor-A (VEGF-A) in pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH) by regulating survivin (SVV).@*METHODS@#A total of 96 neonatal rats were randomly divided into three groups: HPH+VEGF-A group, HPH group, and control group. Each group was further randomly divided into 3-, 7-, 10-, and 14-day subgroups (@*RESULTS@#The HPH group had a significantly higher mean RVSP than the control and HPH+VEGF-A groups at each time point (@*CONCLUSIONS@#Prophylactic intratracheal administration of exogenous VEGF-A in neonatal rats with HPH can inhibit pulmonary vascular remodeling and reduce pulmonary arterial pressure by upregulating the expression of SVV in the early stage of hypoxia. This provides a basis for the interventional treatment of pulmonary vascular remodeling in neonatal HPH.

Efficacy of Baxian Xiaoyaotang Against Ankylosis of Wind-Cold-Dampness Obstruction Syndrome After Acute Achilles Tendon Rupture Surgery and Its Influences on TGF-β1， IGF-1， and EGF / 中国实验方剂学杂志

Objective:To investigate the efficacy of Baxian Xiaoyaotang （BXT） in treating ankylosis of wind-cold-dampness obstruction syndrome after acute Achilles tendon rupture surgery and its effects on transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， insulin-like growth factor-1 （IGF-1）， and epidermal growth factor （EGF）. Method:According to the visiting sequence， 66 patients with fresh closed Achilles tendon rupture were included and randomly divided into a treatment group （<italic>n</italic>=33） and a control group （<italic>n</italic>=33）. Patients in both groups underwent surgical repair， followed by immobilization in long-leg brace， which was then replaced by the boot brace in the fourth week， with the plantar-flexion angle adjusted correspondingly. Six weeks later， the brace was removed for accelerated functional rehabilitation training. On this basis， patients in the treatment group were further instructed to fumigate and wash the affected Achilles tendon with BXT， twice a day， for 45 d. The Leppilahti Achilles tendon performance scores and American Orthopaedic Foot and Ankle Society （AOFAS） ankle-hindfoot scores between the two groups were compared at the time of brace removal and the third， sixth， and twelfth months after surgery. The strength of triceps surae on the affected side was evaluated at the last follow-up visit. The serum TGF-<italic>β</italic>₁， IGF-1， and EGF levels were detected before and after treatment. The wind-cold-dampness obstruction syndrome scores， symptom scores， the changes in foot dorsiflexion angle， and the overall clinical efficacy were compared. Result:The changes in scores of patients receiving different treatment measures did not synchronize. After the removal of brace， the Leppilahti Achilles tendon performance score and AOFAS ankle-hindfoot score determined at three time points in the treatment group were higher than those in the control group （<italic>P</italic><0.05）. At the last follow-up visit， the good-to-excellent rate of muscle strength in the treatment group was 93.94% （31/33）， higher than 72.73% （24/33） in the control group （χ²=0.031，<italic>P</italic><0.05）， implying that the strength of triceps surae in the treatment group was better recovered. After treatment， the serum TGF-<italic>β</italic>₁， IGF-1， and EGF levels in both groups were increased in contrast to those before treatment （<italic>P</italic><0.05）， and these levels in the treatment group were all higher than those in the control group （<italic>P</italic><0.05）. The foot dorsiflexion angle and the wind-cold-dampness obstruction syndrome score in the treatment group were superior to those in the control group （<italic>P</italic><0.05）. The overall response rate of the treatment group was 90.91% （30/33）， higher than 75.76% （25/33） of the control group （<italic>χ</italic>²=6.981， <italic>P</italic><0.05）. No adverse reactions occurred during the treatment. Conclusion:The external fumigation and washing with BXT alleviates both the clinical symptoms and traditional Chinese medicine （TCM） syndrome， improves the joint function score， triceps surae strength， and other indicators， elevates the serum TGF-<italic>β</italic>₁， IGF-1， and EGF levels， and enhances the strength and toughness of Achilles tendon of patients with ankylosis due to wind-cold-dampness obstruction after the acute Achilles tendon rupture surgery. Its clinical efficacy is better than that of functional rehabilitation training.

Liver Tissue-specific Genes IGFALS,CYP3A4,SLC22A1 and CYP2E1 May be Associated with Poor Prognosis of Liver Cancer / 中国医学科学院学报

Objective To explore the function and mechanism of related genes in the occurrence and development of liver cancer, and the possibility of key genes as potential biomarkers and prognostic indicators for the treatment of liver cancer.Methods We selected 4 datasets(GSE57957, GSE121248, GSE36376 and GSE14520)from the GEO database.With

IgA removal by plasma component Ⅱ solution: A comparative study of different filter membrane combinations / 中国输血杂志

【Objective】 To compare the effect of different combinations of filter membranes on the removal of IgA by component Ⅱ solution. 【Methods】 The dissolved solution of component Ⅱ was filtered with different combinations of filter membranes, and the turbidity, IgA residue, molecular size distribution and purity were compared. 【Results】 After filtering through the combination of NA-16+ Millpore 0.5μ, NA-16+ EmphazeTMAEX HP, and ZetaPlus™ + Emphaze™AEX HP filter membranes, the turbidity of the filtrate decreased by 35.5%(22.4/63.1), 39.2%(24.8/63.3) and 59.8%(37.4/62.5), the IgA residue decreased by 5.8%(14.77/253.70), 20.0%(50.90/254.00) and 44.3%(112.13/253.33), respectively.Molecular size distribution was 99.60%, 99.85% and 100%, and the purity was 100%, 100% and 100%, respectively. 【Conclusion】 The combination of ZetaPlus™ + Emphaze™AEX HP filter membrane can not only effectively remove IgA in the dissolution solution of component Ⅱ with other quality indicators remaining high-level, which can be used in IVIG large-scale production process.