Objective:To explore the effects of imperatorin(IMP)on airway remodeling in the bronchial asthma mice,and to elucidate the possible mechanisms.Methods:Forty SFP male BALB/c mice were randomly divided into control group,model group,low dose of IMP group(IMP-L group),high dose of IMP group(IMP-H group)and dexamethasone group,with 8 mice in each group.Except for contol group,the mice in the other groups were injected with an ovalbumin(OVA)suspension intraperitoneally to induce the asthma models.After one week,the daily asthma symptoms of the mice were observed and scored.After 8 weeks,the enhanced pause(Penh)values of the mice in various groups were detected to evaluate the airway reactivities.The percentages of eosinophils in the bronchoalveolar lavage fluid(BALF)of the mice in various groups were detected by flow cytometry.The levels of serum IgE,interleukin interferon-gamma(IL)-13,IL-5,IL-4 and interferon-gamma(IFN-γ)in BALF of the mice in various groups were measured by enzyme-linked immunosorbent assay(ELISA)method.HE,PAS and Masson staining were applied to observe the pathomorphology,the number of goblet cells and collagen deposition of the lung tissue of the mice in various groups.Immunohisto chemistry method was applied to detect the expressions of α-smooth muscle actin(α-SMA)and mouse mammary tumor virus(MMTV)wingless type MMTV intergration site family member 5A(Wnt5A)proteins in lung tissue of the mice in various groups.The expression levels of Wnt5A,cellular myelocytomatosis oncogene(c-Myc),β-catenin and α-SMA in lung tissue of the mice in various groups were detected by Western blotting method.The expression levels of α-SMA protein in lung tissue of the mice in various groups were detected by immunofluorescence method.Results:Compared with control group,the score of asthma symptoms of the mice in model group was increased(P<0.01);the Penh value was significantly increased(P<0.01);the serum IgE levels and the levels of IL-13,IL-5,IL-4 in BALF,as well as the percentage of eosinophils(EOS)in BALF were significantly increased(P<0.05 or P<0.01),and the level of IFN-γ was reduced(P<0.05);the expression levels of α-SMA and Wnt5A proteins in lung tissue were markedly increased(P<0.01);the expression levels of proteins associated with the Wnt/β-catenin signaling pathway in the lung tissue were significantly increased(P<0.01);the immofluorescence method results showed the expression level of α-SMA protein in lung tissue was significantly increased(P<0.01).Compared with model group,the scores of asthma symphtoms of the mice in IMP-L group,IMP-H group,and dexamethasone group were decereased(P<0.01),and the Penh values of the mice in IMP-H group were decreased(P<0.05);the serum IgE levels and the levels of IL-13,IL-5,IL-4 in BALF,as well as the percentages of EOS in BALF of the mice in IMP-L group,IMP-H group,and dexamethasone group were decreased(P<0.05 or P<0.01),and the levels of IFN-γ were increased(P<0.05);the expression levels α-SMA and Wnt5A proteins in lung tissue were decreased(P<0.05 or P<0.01);the expression levels of proteins related to the Wnt/β-catenin signaling pathway in the lung tissue were decreased(P<0.05 or P<0.01);the immunofluorescence method results showed that expression levels of the α-SMA protein in the lung tissue were reduced(P<0.05 or P<0.01).Conclusion:IMP has an improving effect on airway remodeling in the asthmatic mice and can inhibit the expression levels of Wnt/β-catenin pathway-related proteins.

Objective:To observe the clinical efficacy of exercise-based acupuncture in treating ischemic stroke and its effects in improving the patient's motor function and daily living ability. Methods:A total of 106 patients with motor dysfunction due to cerebral infarction were randomized into a trial group and a control group,each consisting of 53 cases.Both groups received conventional rehabilitation;in addition,the control group was given point-toward-point acupuncture at scalp points,and the trial group was offered exercise-based acupuncture,3 times weekly for 4 consecutive weeks.Before treatment,after 2 and 4 weeks of treatment,and at the 2-month follow-up,the Fugl-Meyer assessment(FMA)scale,Lovett scale for muscle strength,modified Ashworth scale(MAS),and activities of daily living(ADL)scale were used to assess the patient's motor function,muscle strength,muscle tension,and daily living ability. Results:After treatment,both groups gained improvements in motor function and daily living ability;after 4-week treatment and at the 2-month follow-up,the trial group had higher FMA and ADL scores than the control group(P<0.05).The MAS score decreased after treatment in both groups;after 2 and 4 weeks of treatment and at the 2-month follow-up,the MAS score was lower in the trial group than in the control group(P<0.05).After the intervention,the Lovett score increased in both groups;after 4 weeks of treatment,the Lovett score was higher in the trial group than in the control group(P<0.05). Conclusion:Based on routine rehabilitation,exercise-based acupuncture and scalp point-toward-point acupuncture both can improve the motor function and daily living ability in ischemic stroke patients;exercise-based acupuncture performs better than scalp point-toward-point acupuncture.

Objective:To explore the influence of tomoxetine hydrochloride on the cognitive processing of children with attention deficit hyperactivity disorder (ADHD).Methods:From January 2018 to July 2021, 62 ADHD children who were treated with tomoxetine hydrochloride for the first time for(8±4) weeks were selected as the ADHD group.And 62 healthy children matched with age and sex were selected as the healthy control group.Pre-test and post-test by the Das-Naglieri: Cognitive Assessment System(DN: CAS) were performed to evaluate the cognitive function of all individuals.The differences of cognitive processing in pre-treatment and post-treatment of ADHD group were compared with those in healthy control group.The difference between before and after treatment of ADHD group was also compared.SPSS 26.0 statistical software was adopted for statistical analysis.The scores of ADHD group pre-treatment and post-treatment were compared by paired sample t-test, and the scores of ADHD group pre-treatment and post-treatment were compared with those of healthy control group by independent sample t-test. Results:Compared with healthy control group, there were lower of planning score((18.77±5.92) vs (28.56±5.55)), attention score((22.24±5.93) vs (29.56±6.16)), simultaneous processing ((34.21±7.75) vs (37.61±6.29)), successive processing((30.37±7.12) vs (33.74±5.43)), and the total scores((105.60±21.29) vs (134.84±22.87)) in ADHD group before treatment, and there were significant differences( t=9.49, 6.74, 2.68, 2.96, 7.36, all P<0.05). Compared with healthy control group, there were lower of planning score ((22.13±5.99)s), attention score((25.26±7.11) with significant difference( t=6.20, 3.60, both P<0.05) in ADHD group after treatment.And there was no significant difference in the simultaneous processing test and the successive processing test after treatment compared with the healthy control group(both P>0.05). In ADHD group, the scores of planning, simultaneous processing, attention, successive processing and the total score were significantly higher after treatment than those before treatment and there were significant differences( t=-6.03, -4.13, -4.77, -5.48, -8.59, all P<0.05). (2) Compared with the healthy control group, there were lower of matching number score and other 8 sub-test scales in DN: CAS test in ADHD group before treatment, and the differences were statistically significant (all P<0.05). Meanwhile, there were still lower of matching number score and other 4 sub-test scales in DN: CAS test in ADHD group after treatment, and the differences were statistically significant (all P<0.05). The matching number score and other 10 sub-test scales in DN: CAS test in ADHD group after treatment were all higher than those of before treatment(all P<0.05). Conclusion:The planning, attention, simultaneous processing, successive processing and total cognitive function of ADHD children were significantly improved after treatment with tomoxetine hydrochloride, special for simultaneous processing and successive processing.

Ferroptosis is defined as an iron-dependent, non-apoptotic cell death pathway, with specific morphological phenotypes and biochemical changes. There is a growing realization that ferroptosis has significant implications for several neurodegenerative diseases. Even though ferroptosis is different from other forms of programmed death such as apoptosis and autophagic death, they involve a number of common protein molecules. This review focuses on current research on ferroptosis and summarizes the cross-talk among ferroptosis, apoptosis, and autophagy that are implicated in neurodegenerative diseases. We hope that this information provides new ideas for understanding the mechanisms and searching for potential therapeutic approaches and prevention of neurodegenerative diseases.
Apoptosis ; Autophagy ; Cell Death ; Ferroptosis ; Humans ; Neurodegenerative Diseases

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause of multidrug resistance (MDR), which is a significant hurdle to the success of chemotherapy in many cancers. Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR. Olmutinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been approved in South Korea for advanced EGFR T790M-positive non-small cell lung cancer (NSCLC). Here, we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABC transporter subfamily G member 2 (ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [I]-iodoarylazidoprazosin (IAAP). However, olmutinib neither altered ABCG2 expression at protein and mRNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly, olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.

Objective To explore the influence of Methylphenidate Hydrochloride prolonged-release tablets on the cognitive processing of children with attention deficit hyperactivity disorder (ADHD).Methods Thirty ADHD children and 30 healthy controls were enrolled in this study,and the ADHD subjects were treated with Methylphenidate Hydrochloride prolonged-release tablets for (28 ± 3) days.Pre-test and post-test by the Das-Naglieri:Cognitive Assessment System(DN:CAS) were done to evaluate the cognitive function of all individuals.The differences of cognitive processing in pre-treatment and post-treatment of ADHD group with healthy control group were compared.The difference between before and after treatment of ADHD was also compared.Results Compared with healthy control group,there were lower of planning score [(21.86 ± 4.61) scores vs.(29.33 ± 5.06) scores],attention score [(25.00 ± 4.57) scores vs.(29.83 ± 3.79) scores],and the total scores [(111.93 ± 13.95) scores vs.(127.26 ±15.53) scores] in ADHD group,and there were significant differences (t =-5.976,-4.455,-4.023,all P ＜0.05).The matching number,planned codes,planned connections,expressive attention,number detection and receptive attention scores were also lower in ADHD group,and there were significant differences (t =-4.787,-3.703,-4.991,-2.216,-2.488,-3.219,all P ＜ 0.05).Compared with healthy control group,there were lower of planning score with significant difference [(25.53 ± 4.98) scores vs.(29.33 ± 5.06) scores,t =-2.931,P ＜ 0.05] in ADHD group after treatment,matching number and planned codes were lower with significant difference (t =-2.654,-2.044,all P ＜ 0.05) in ADHD group after treatment.In ADHD group,the scores of planning [(25.53 ± 4.98)scores vs.(21.86 ± 4.61) scores],simultaneous processing [(36.10 ± 7.10) scores vs.(34.13 ± 6.04) scores],attention [(27.90 ± 5.69) scores vs.(25.00 ± 4.57) scores] and the total score [(121.50 ± 16.55) scores vs.(111.93 ± 13.95) scores] were significantly higher after treatment than that before treatment and there were significant differences (t =-5.679,-2.949,-3.869,-5.963,all P ＜ 0.05);matching number,planned codes,planned connections,nonverbal matrices,number detection,receptive attention and word series were significantly higher after treatment than that before treatment,and there were significant differences (t =-2.528,-3.209,-3.890,-2.276,-4.489,-2.208,-2.373,all P ＜ 0.05).Conclusion The Methylphenidate Hydrochloride prolonged-release tablets can improve the function of cognitive processing in children with ADHD,especially in attention.

Objective To evaluate the cardioprotection induced by ischemic preconditioning ( IPC) and hypoxic preconditioning ( HPC) which were carried out by using the double cardiopulmonary bypass ( CPB) circuits in in vivo hearts of dogs. Methods Eighteen healthy male dogs, weighing 17?5-24?5 kg, aged 13-24 months, were divided into 3 groups ( n=6 each) using a random number table: my?ocardial ischemia?reperfusion group (group I∕R), IPC group and HPC group. The double CPB circuits were established as follows: systemic and coronary circulation, and independent systemic and coronary cir?culation was carried out. In group IPC, the aorta was clamped, and the coronary circulation pump was sus?pended for 5 min followed by 5 min opening, repeating for 3 cycles. In group HPC, the aorta was clamped, the coronary circulation was started, and pure nitrogen was insufflated for 5 min followed by 5 min of oxygen insufflation, repeating for 3 cycles. CPB was performed for 1 h starting from the time point immediately after IPC or HPC. Before splitting of sternum ( T1 ) , after establishment of double CPB circuits ( T2 ) , at the end of preconditioning ( T3 ) , and at 60 and 120 min after restoration of spontaneous heart
beat ( T4,5 ) , heat rate, mean arterial pressure, central venous pressure, left ventricular end?systolic pres?sure, left ventricular end?diastolic pressure and the maximum rate of increase∕decrease of left ventricular pressure were recorded. Blood samples were collected from the right internal jugular vein at T1 and T4,5 for determination of serum cardiac troponin I concentrations. The animals were sacrificed after determination of the parameter or after blood sampling at T5 , myocardial specimens were obtained for examination of the ul?trastructure and for detection of apoptosis in cardiomyocytes, and apoptosis index was calculated. Before aortic clamping, immediately after aortic unclamping and at 30 min after aortic unclamping, myocardial specimens were obtained for determination of ATP contents in cardiomyocytes. Results Compared with I∕R group, left ventricular end?systolic pressure was significantly increased, and the serum cardiac troponin I concentrations were significantly decreased at T4,5 , the myocardial ATP contents were significantly in?creased immediately after aortic unclamping and at 30 min after aortic unclamping, apoptosis index was sig?nificantly decreased ( P<0?05 or 0?01) , and the pathological changes were significantly attenuated in IPC and HPC groups. Compared with group IPC, the myocardial ATP contents were significantly increased (P<0?05), and the pathological changes were attenuated in group HPC. Conclusion Both HPC and IPC can exert cardioprotection when carried out by using the double CPB circuits, and HPC provides better cardioprotection than IPC in in vivo hearts of dogs.

OBJECTIVETo explore the impacts on the fine movement of upper extremity with flaccid paralysis in stroke treated with acupuncture and motor imagery.

METHODSSixty-two cases of flaccid paralysis of upper extremity in stroke were randomized into an observation group (30 cases) and a control group (32 cases). In the control group, the conventional western medication and the passive movement of the extremity were applied. Additionally, the penetrating needling technique was used at the head points [penetrating needling from Baihui (GV 20) to Taiyang (EX-HN 5)] and the local affected extremity [penetrating needling from Jianyu (LI 15) to Binao (LI1 14), from Quchi (LI 11) to Shaohai (HT 3), from Waiguan (TE 5) to Neiguan (PC 6), etc]. The needles were retained for 30 min. In the observation group, on the basic treatment as the control group, during the needle retaining, the motor imagery therapy was supplemented. The treatment was given once a day, 5 treatments a week, for 4 weeks totally in the either group. The scores in the action research arm test (ARAT) and the modified Fugl-Meyer assessment (FMA) were recorded at the moment of enrollment, in 2 and 4 weeks of treatment, in the 6th and 8th weeks, as well as after 90 days separately.

RESULTS(1) ARAT score: since the 2nd week, ARAT scores in the observation group were all improved significantly as compared with those in the control group at the each time points (all P<0. 05). In the observation group, the scores were improved significantly in the pair comparison at the time points (all P<0. 05). In the control group, the score in the 2nd week was not different significantly as compared with that before treatment (P>0. 05), but the scores at the rest time points were improved significantly in the pair comparison (all P<0. 05); (2) FMA score: in the 2nd week and on the 90th day, FMA score in the observation group was higher significantly than those in the control group (both P < 0. 05). In the observation group, the scores were all improved significantly in the pair comparison at the time points (all P<0. 05). In the control group, except that in comparison between the 90th day and the 8th week (P>0. 05), the results were all P<0. 05 at the rest time points.

CONCLUSIONThe early intervention of the combined therapy of acupuncture and motor imagery effectively promotes the recovery of the coordination function and the fine movement of upper extremity, especially the improvements of the fine movement in stroke at flaccid paralysis stage. The efficacy is better than the single acupuncture treatment.

Acupuncture Therapy ; Adult ; Aged ; Combined Modality Therapy ; Female ; Humans ; Imagery (Psychotherapy) ; Imagination ; Male ; Middle Aged ; Motor Activity ; Paraplegia ; etiology ; physiopathology ; psychology ; therapy ; Stroke ; complications ; therapy ; Upper Extremity ; physiopathology

Objective To observe the ultrasonic manifestation of metatarsal fatigue fractures and probe into the clinical values of ultrasonic diagnosis and follow-up to the disease.Methods The clinical data and sonographic features of 30 cases with metatarsal fatigue fracture confirmed by X-ray and CT were analyzed retrospectively.Results All the subjects in this study were metatarsals insufficiency fractures located in the second or third diaphysis.2D-ultrasound found microfracture in the cortex and the periosteal elevation by increased vascularity in the early stage.During the 3-month follow-up,thickened cortex and callus shown as the shape of mushroom or cauliflower and a great amount of neovascularisation were visualised with color Doppler flow imaging.Then,the cortex surface became gradually changing from rough to smooth and obvious posterior shadows were observed with the illness progression.Conclusions Ultrasonography could be used to detect the cortical continuity,callus characteristics and blood flow perfusion of fatigue fracture in the different damage stages.