AIM:To investigate the impact of aquaporin 4(AQP4)expression inhibition on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion(I/R)injury,and to elucidate its underlying mechanism.METHODS:Cerebral I/R injury was induced in mice via transient middle cerebral artery occlusion(tMCAO).Totally 60 mice were randomly divided into sham group,I/R group,AQP4 inhibition group,and 3-methyladenine(3-MA)group,with 15 mice in each group.Among them,the mice in sham and I/R groups received intraperitoneal injections of normal saline,while those in AQP4 inhibition group and 3-MA group received intraperitoneal injections of AER-271(2 mg·kg-1·d-1)and AER-271+3-MA(2 mg·kg-1·d-1)for 3 d,respectively,once per day.Longa score was adopted to assess the neu-rological function,and to record changes in body weight.Cerebral infarction volume and histopathological alterations were evaluated using hematoxylin-eosin staining.Western blot analysis was performed to determine the levels of AQP4,LC3-Ⅱ,P62 and cleaved caspase-3,while the LC3-Ⅱ,P62,cleaved caspase-3 and NeuN(neuronal marker)colocalization and expression assessment were conducted with immunofluorescence.RESULTS:The mice in I/R and AQP4 inhibition groups exhibited extensive cerebral infarction,cerebral edema,and elevated Longa scores.However,in comparision to I/R group,the mice in AQP4 inhibition group showed significantly reduced cerebral infarct volume,cerebral edema vol-ume,and Longa score(P<0.05).Additionally,in contrast to sham group,the mice in I/R group displayed increased ex-pression of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.01),accompanied by decreased body weight and P62 expression(P<0.05 or P<0.01).Furthermore,compared with I/R group,the mice in both AQP4 inhibition group and 3-MA group demonstrated a decrease in the expression levels of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.05 or P<0.01),along with increased body weight and P62 expression(P<0.05 or P<0.01).Nonetheless,no significant differences were ob-served between AQP4 inhibition group and 3-MA group regarding Longa score,cerebral infarct volume,body weight,and the expression of AQP4,LC3-Ⅱ,cleaved caspase-3 and P62.CONCLUSION:Inhibition of AQP4 expression signifi-cantly reduces cerebral infarction area and nerve injury severity in tMCAO mice.Moreover,AQP4 expression inhibition decelerates autophagy and apoptosis after cerebral infarction,with the additional autophagy inhibitor showing no notable impact on the protective effect of AQP4 inhibition.

Objective:To explore the influence of airway mucus plugs on patients with bronchial asthma and its management.Methods:In this cross-sectional study, from January 2020 to June 2022, 100 patients who were diagnosed with asthma and underwent chest CT examination in the Outpatient Department of Peking University Third Hospital were included. The chest CT results and medical history, pulmonary function, fractional exhaled nitric oxide (FeNO), blood routine, total allergen IgE, Aspergillus fumigatus M3 allergen-specific IgE antibody test results were collected. According to the results of chest CT, the asthma patients were divided into group with mucus plugs and those without mucus plugs. Distribution of airway mucus plugs and the mucus plug scores based on lung segments were calculated. The relationships of mucus plugs with medical history, pulmonary function [These included before and after the bronchodilation test, forced vital capacity percent of predicted value (FVC%pred), forced expiratory volume in one second percent of predicted value (FEV 1%pred), FEV 1/FVC, peak expiratory flow percent of predicted value (PEF%pred), maximal mid-expiratory flow percent of predicted value (MMEF%pred), maximal expiratory flow at 25%, 50%, 75% of vital capacity remaining percent of predicted value (MEF 25%pred, MEF 50%pred, MEF 75%pred)], FeNO, and peripheral blood eosinophil (Eos) counts were analyzed. The logistic regression model was used to analyze whether airway mucus plug was a risk factor for asthma exacerbation, and the corresponding intervention strategies were explored. Results:Among the 100 patients with asthma, 24 cases were in the mucus plug group and 76 cases were in the non-mucus plug group. The distribution of mucus plug was more common in the lower lungs (30.53% and 9.16% in the lower and upper lobe of left lung, respectively; 29.01%, 14.50% and 16.80% in the lower, middle and upper lobe of right lung, respectively). The average score of mucus plug was (4.42±3.12) points. The body mass index (BMI), the number of visits to a doctor due to asthma exacerbations, FeNO, peripheral blood Eos counts in the mucus plug group were higher than those in the non-mucus plug group [(24.95±4.34) vs (23.22±2.91) kg/m 2, 0(0, 1) vs 0(0, 0), 97(37, 169) vs 31(18, 59) ppb (1 ppb=1×10 -9), 0.41(0.15, 0.70) vs 0.18(0.09, 0.37)×10 9/L](all P<0.05), and FVC%pred, FEV 1%pred, FEV 1/FVC, PEF%pred, MEF 50%pred, MEF 25%pred, MMEF%pred, MEF 75%pred were lower than those in the non-mucus plug group [(87.49±19.32)% vs (97.34±14.24)%, (76.49±19.58)% vs (91.07±18.33)%, (72.44±10.91)% vs (79.48±8.13)%, (82.36±24.46)% vs (93.83±18.27)%, (53.03±24.81)% vs (75.75±27.15)%, (46.47±22.92)% vs (64.09±25.90)%, (50.28±23.73)% vs (74.53±26.80)%, (71.30±27.55)% vs (89.92±26.82)%] (all P<0.05). In the group with mucus plug, the airway mucus plug score was positively correlated with the patient′s body weight and the number of peripheral blood Eos counts at enrollment ( r=0.413, 0.478; all P<0.05), and negatively correlated with FVC%pred and FEV 1%pred ( r=-0.576, -0.465; all P<0.05). Logistic regression analysis showed that airway mucus plug score was a risk factor for acute asthma attack ( OR=1.269, 95% CI: 1.031-1.562; P=0.024). Conclusions:Asthma patients have a high incidence of airway mucus plug, which is related to the level of Eos inflammation and body size. Airway mucus plugs can promote airflow obstruction and acute exacerbation of asthma. In clinical practice, appropriate asthma management policies can be formulated for airway mucus plugs to delay the progression of asthma and reduce the number of acute attacks.

Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8%
Critical Illness ; Cross-Sectional Studies ; Echocardiography ; Humans ; Intensive Care Units ; Lung/diagnostic imaging* ; Retrospective Studies

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.

Objective To investigate the effects and mechanism of interleukin 33 (IL-33) on renal tubular injury in mice with lupus nephritis.Methods Twelve-week-old female MRL/lpr mice were randomly divided into model group,IL-33 group and solvent control group with 10 rats in each group.Ten female MRL/MP mice of the same age were used as normal control group.The mice in IL-33 group were intraperitoneally injected with 100 μL of phosphate buffer saline (PBS),containing 2 μg of recombinant mouse IL-33,once a day for 14 days.The mice in control group and the model group were intraperitoneally injected with the same dose of PBS.All the mice were sacrificed at 14 weeks of age.Serum creatinine (Cr) and urea nitrogen (BUN) concentrations were determined by serum separation.The urine in 24 hours was collected testing urinary protein creatinine ratio and urinary protein quantification.The contents of E-cadherin,α-SMA,and JAK/STAT pathway signaling proteins,including JAK2,p-JAK2,STAT1,and p-STAT1,were detected by Western blot.Results The BUN,urinary protein creatinine ratio and urine protein level of the IL-33 group were significantly higher than those of the model group (all P＜0.05).The expression of renal tubular epithelial cells o-SMA in the IL-33 group was higher than that in the model group,and the difference was statistically significant (P＜0.05).Compared with the model group,the expression of E-cadherin in the tubular epithelial cells of IL-33 group decreased and the expression of p-JAK2 and p-STAT1 protein increased,and the differences were all statistically significant (all P＜0.05).Compared with the model group,the levels of JAK2 and STAT1 in IL-33 group change little,and the differences were not statistically significant (all P＞0.05).Conclusions IL-33 can cause tubulointerstitial lesions in lupus mice,and its mechanism may be related to the activation of JAK/STAT pathway.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.

Objective To observe ultrasonographic features and significance of scoring of the lung in preterm infants.Methods Totally 37 preterm infants (preterm group) and 33 term infants (term group) without cardiopulmonary disease nor hypoproteinemia were enrolled,and infants in each group were divided into＜1 week,1-4 weeks and ＞4 weeks subgroup,respectively.All the infants underwent lung ultrasonography and scoring.The ultrasonography scores were compared between preterm infants and term infants among different ages.Results The main ultrasonic manifestations of the lung in preterm infants were diffuse distribution of dense B-lines,with or without " falls sign" suggesting alveolar effusion.The ultrasonographic score of the lung in preterm infants and term infants was (15.24± 2.76) and (12.21 ±3.62),respectively (t=3.962,P＜0.001).There was no statistical difference of ultrasonographyic scores in ＜1 week subgroups between preterm infants and term infants (t =-0.669,P =0.513).There were statistical differences of ultrasonographic scores in 1-4 weeks subgroups and ＞4 weeks subgroups between preterm group and term group (both P＜0.05).In preterm group,the ultrasonographic scores demonstrated no statistical difference among 3 subgroups (F=0.960,P=0.393),whereas statistical difference was found among 3 subgroups in term group (F =4.277,P =0.023).The ultrasonographic score of preterm infants showed negative correlation with gestational age (r=-0.352,P=0.033),and the linear regressive equation was Y=33.805-0.548X.Conclusion The main ultrasonic manifestations of the lung in preterm infants were diffuse distribution of dense B-lines,some with "falls sign" suggesting alveolar effusion,which are more significant in smaller gestational age infants.

Objective To observe the adverse effects of 0.01％ atropine sulfate eye drops on myopic children.Methods A prospective non-randomized controlled trial was conducted.Ninety-nine myopic children (99 right eyes) were randomly assigned to experimental group(55 cases) and control group(44 cases).Myopic children of experimental group wore completely corrected frame glasses,while 0.01％ atropine sulfate eye drop was dropped into each eye once a day before going to bed.Myopic children in control group only wore completely corrected frame glasses.The follow-up time was 4 months.Best corrected visual acuity (BCVA),intraocular pressure (IOP),change of pupil diameter (PD) and amplitude of accommodation,symptoms of discomfort after medication were observed.This study followed the Helsinki declaration and was approved by Ethic Committee of the First Affiliated Hospital of Zhengzhou University.Informed consent was signed by the parents of each patient.Results No significant differences were found in best corrected distance visual acuity (BCDVA),best corrected near visual acuity(BCNVA) and IOP between the two groups before and 4 months after treatment (BCDVA:Fgroup =3.880,P =0.112;Ftime =27.220,P =0.413;BCNVA:Fgroup =5.200,P =0.311;Ftime =38.200,P =0.116,IOP:Fgroup =12.350,P=0.214;Ftime =22.300,P =0.146).After 4 months treatment,the PD was (6.99 ±0.64) mm in the experimental group,which was significantly higher than that before treatment(P＜0.001).The PD of the experimental group was higher than that of the control group after 4 months treatment,and the difference was statistically significant (P＜0.01).The amplitude of accommodation in the experimental group was 14.01 ±3.98 after 4 months treatment.which was 1.20 D lower than that before treatment,the difference was statistically significant (P＜0.01).The amplitude of accommodation of the experimental group was lower than that of the control group after 4 months treatment,the difference was statistically significant (P ＜ 0.01).Four cases (8％) appeared photophobia symptoms.Two cases and 2 cases appeared photophobia for 1 week or 2 weeks,respectively.However this symptom would relieve after wear sunglasses or sunshade caps in outdoor activities.One case (2％) appeared ocular itching and swelling after 1 month treatment,but disappeared after withdrawal.There were no other uncomfortable symptoms such as near sight blurring.Conclusions In mainland of China,the BCDVA,BCNVA and IOP of myopic children are stable;the PD is dilated and the amplitude of accommodation is decreased slightly after 4 months treatment of 0.01％ atropine,and 10％ children appear photophobia,but do not affect their study and life.

Objective To compare the changes of diopter and axial length(AL) m 2 years after wearing orthokeratology lens,rigid gas permeable contact lens (RGPCL) and spectacles in adolescent myopia,and evaluate the control effects of different methods on adolescent myopia.Methods Prospective clinical study.The date of 99 eyes of 50 adolescent myopia cases wearing orthokeratology,95 eyes of 48 adolescent myopia cases wearing RGPCL,and 100 eyes of 50 adolescent myopia cases wearing full correction single vision spectacles were collected from June 2012 to June 2014.The follow-up time was 2 years.The status of diopter and AL before and wore mirror after 2 years and the uncorrected visual acuity (UCVA) in group of orthokeratology were recorded.The examinations were repeated after 2 years without wearing orthokeratology and RGPCL at least 30 days.Results There was no statistical difference in age,refractive status and AL among three groups before wearing the mirror.After wearing for 2 years,AL and spherical equivalent in three groups were increased (F =278.43,140.12;all P ＜ 0.01).The increase of AL and SE was as follows:orthokeratology group (0.30 ± 0.39) mm,(0.83 ±0.97) D;RGPCL group (0.55 ± 0.41) mm,(1.55 ± 0.63) D;spectacles group (0.59 ± 0.34)mm,(1.73 ± 0.62)D.The increase of orthokeratology group was the least,and there was no statistical difference between the other two groups.UCVA was significantly improved at each time point after wearing orthokeratology(F =486.38,P ＜0.01).Conclusion In the three optical correction methods of orthokeratology,RGP and spectacles,the ortho-keratology is the best on controlling adolescent myopia,and no difference between the other two.At the same time,wearing orthokeratology can also significantly improve UCVA in myooia cases.

Objective To analysis the clinical features,diagnosis,treatment and prognosis of adrenal eosinophilic tumor with low testosterone levels.Methods The clinical data of a 22 years old male patient with adrenal eosinophilic tumor and low testosterone levels was analyzed.Blood pressure was 151/88 mmHg.The patient got bilateral gynecomastia.His bilateral testicular was soft and became smaller,with short penisr.Endocrine examination results showed:Estradiol 666 pg/ml,Prolactin 19.08 ng/ml,Testosterone 0.18 ng/ml,follicle stimulating hormone ＜ 0.2 U/L.The CT showed the mass density of soft tissue in the left adrenal region with diameter 7 cm,which was inhomogeneous and enhanced.There were many small vessels enhanced in the CT arterial phase,and the blood flow in the tumor was abundant.Clinical diagnosis of left adrenal tumor was pheochromocytoma.The patient underwent laparoscopic left adrenal tumor resection.The left adrenal gland was located in the superior pole of the left kidney,and there was an independent supply of the artery.Results Pathological result showed the tumor weigh was 60 g,7 cm in diameter and brown in section.The tumor cells were arranged in solid nests or acini,with more eosinophilic granules in cytoplasm.The nuclei was round and the nucleoli was located in the center,had clusters of pleomorphic and clustered cells.The tumor was wrapped in a thick fibrous envelope,mainly consisted of eosinophils,granulation tissue.There was no necrosis,mitosis,and vascular invasion.Immunohistochemical staining showed that the expression of CD56 and syn protein was positive.Pathological diagnosis was left adrenal eosinophilic tumor.After 4 months,the blood testosterone levels rose to 3.90 ng/ml,the blood pressure returned to normal (118/75 mmhg).The estradiol (21 pg/ml) was significantly inhibited.The patient began to appear beards and breasts became smaller.There were no signs of clinical or imaging recurrence.After 16 months follow-up,serum testosterone was 4.68 ng/ml and serum estrogen levels dropped to 33 pg/ml.Semen routine showed no sperm.Conclusions The clinical morbidity of functional adrenocortical oncocytoma with low testosterone levels and high estradiol levels is low.The pathological components are mainly eosinophilic granulation tissue.The adrenocortical oncocytoma are rare and preoperative diagnosis is difficult.Clinical manifestation,imaging examination and adrenal biochemistry examination should be considered to determine the localization and qualitative of tumor.Minimally invasive surgery is an effective treatment.The close follow-up after operation is essential.