Objective:To explore the effects of mechanical ventilation（MV）at birth transition on lung pathophysiology and pathobiology in a very preterm animal model.Methods:Based on the model of respiratory distress syndrome（RDS）in very preterm rabbits at gestational age 26（term 31）days well established by the research group using perinatal medication and lung-protective ventilation strategies（very low tidal volume 1-3 mL/kg），we conducted a secondary data analysis. The studied rabbits were re-grouped according to the MV length（≤3 h，3-6 h，6-9 h，9-12 h，and >12 h）. The changes in lung mechanics，histopathology，phospholipid biochemistry，and mRNA relative expression of inflammatory/growth factor in lung tissue were evaluated over the time course of MV. The trend of each variable was tested by ANOVA trend test（ F trend）and Jonckheere-Terpstra trend test（ J-T value）with corresponding P value. Results:With the prolonged MV length，there was improved mean dynamic compliance of respiratory system（ F trend=16.722， P trend<0.001），along with decreased mean peak inspiratory pressure（ F trend =42.226， P trend<0.001）. The content of total phospholipids，disaturated phosphatidylcholine（ J-T=1 222，1 197， P trend=0.018，0.034，respectively）and total protein（ J-T=1 247 ，P trend= 0.009）in bronchoalveolar lavage fluid gradually increased. The wet lung weight in the ≤3 h group was significantly higher than in the other groups（ F=6.819， P<0.001）. The lung injury score（total，or hemorrhage，or inflammation）had progressive exacerbation in the ≤3 h，3-6 h and 6-9 h groups. The lung tissue mRNA expression of major proinflammatory cytokines increased modestly over the time groups in contrast to decreased expression of growth factors，of which the change of keratinocyte growth factor reached statistical significance（ J-T=531， P trend =0.034）. Conclusion:In the 26-day very preterm rabbits，with prolonged MV time，the content of surfactant phospholipid in the alveolar increased gradually，the lung compliance and lung fluid clearance gradually improved. Nevertheless，ventilator-induced lung injury remained evolving. The study warrants further study on the pathogenesis and protective strategies of early postnatal acute lung injury and chronic lung disease.

Objective:To explore the effects of mechanical ventilation（MV）at birth transition on lung pathophysiology and pathobiology in a very preterm animal model.Methods:Based on the model of respiratory distress syndrome（RDS）in very preterm rabbits at gestational age 26（term 31）days well established by the research group using perinatal medication and lung-protective ventilation strategies（very low tidal volume 1-3 mL/kg），we conducted a secondary data analysis. The studied rabbits were re-grouped according to the MV length（≤3 h，3-6 h，6-9 h，9-12 h，and >12 h）. The changes in lung mechanics，histopathology，phospholipid biochemistry，and mRNA relative expression of inflammatory/growth factor in lung tissue were evaluated over the time course of MV. The trend of each variable was tested by ANOVA trend test（ F trend）and Jonckheere-Terpstra trend test（ J-T value）with corresponding P value. Results:With the prolonged MV length，there was improved mean dynamic compliance of respiratory system（ F trend=16.722， P trend<0.001），along with decreased mean peak inspiratory pressure（ F trend =42.226， P trend<0.001）. The content of total phospholipids，disaturated phosphatidylcholine（ J-T=1 222，1 197， P trend=0.018，0.034，respectively）and total protein（ J-T=1 247 ，P trend= 0.009）in bronchoalveolar lavage fluid gradually increased. The wet lung weight in the ≤3 h group was significantly higher than in the other groups（ F=6.819， P<0.001）. The lung injury score（total，or hemorrhage，or inflammation）had progressive exacerbation in the ≤3 h，3-6 h and 6-9 h groups. The lung tissue mRNA expression of major proinflammatory cytokines increased modestly over the time groups in contrast to decreased expression of growth factors，of which the change of keratinocyte growth factor reached statistical significance（ J-T=531， P trend =0.034）. Conclusion:In the 26-day very preterm rabbits，with prolonged MV time，the content of surfactant phospholipid in the alveolar increased gradually，the lung compliance and lung fluid clearance gradually improved. Nevertheless，ventilator-induced lung injury remained evolving. The study warrants further study on the pathogenesis and protective strategies of early postnatal acute lung injury and chronic lung disease.

Objective To investigate the interventional effect and mechanism of a novel ampelopsis hydrogel on dampness-heat accumulation syndrome of gouty arthritis. Methods A total of 90 patients with gouty arthritis who met the diagnostic criteria of western medicine and were differentiated as damp-heat accumulation syndrome of traditional Chinese medicine(TCM) were randomly divided into treatment group, control group and blank group, with 30 patients in each group. The blank group was treated with etoricoxib only, the control group was treated with etoricoxib combined with ampelopsis hydrogel, and the treatment group was treated with etoricoxib combined with external application of ampelopsis hydrogel. The clinical efficacy, time to symptom improvement, safety, comfort, changes in syndrome scores of TCM, serum inflammatory factors[C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), erythrocyte sedimentation rate (ESR)], NF-κB signaling pathway-related proteins, Visual Analogue Scale (VAS) scores for pain, and joint mobility were compared among the three groups before and after treatment. Results The total effective rates in the treatment group and control group were 93.33% and 90.00%, respectively, which were higher than 70.00% in the blank group (P < 0.05). The time for improvement of pain, redness, tenderness, and limited joint mobility in the treatment group was shorter than that in the control group and blank group (P < 0.05). After 7 days of treatment, the TCM syndrome score in the treatment group was lower than that in the control group and blank group, and the levels of serum CRP, TNF-α, and ESR and the expressions of NF-κB signalingpathway-related proteins P50 and P65 in the treatment group and control group were lower than those in the blank group (P < 0.05). After 7 days of treatment, the VAS score in the treatment group was lower than that in the control group and blank group, and the comfort score in the treatment group was higher than that in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions among the three groups (P>0.05). Conclusion The effect of ampelopsis hydrogel in treating gouty arthritis is better than that of ampelopsis paste, and its mechanism may be related to the regulation of the NF-κB pathway and inhibition of inflammatory factor expression. The hydrogel is easy to use, hygienic, and comfortable, and is expected to become a safe, effective, and convenient external medicine for gouty arthritis.

Objective To explore the changes in periretinal defocus and visual quality after femtosecond laser-assis-ted in situ keratomileusis(FS-LASIK).Methods Fifty-one myopic patients(102 eyes)who underwent FS-LASIK at the Ineye Hospital of Chengdu University of Traditional Chinese Medicine from March to May 2023 were selected for the study,including 27 females(54 eyes)and 24 males(48 eyes).The defocus around the retina was measured using a multispectral refraction topography,and the total refraction difference value(TRDV)was recorded.The refraction difference value(RDV)in four quadrants:superior RDV(RDV-S),inferior RDV(RDV-I),nasal RDV(RDV-N),and temporal RDV(RDV-T),as well as the RDV in the concentric ring areas corresponding to 10°,20°,30°,40°,and 53° from the fovea of the mac-ula(represented as RDV 0°-10°,RDV 10°-20°,RDV 20°-30°,RDV 30°-40°,and RDV 40°-53°,respectively)were also re-corded.The objective scattering index(OSI),Strehls ratio(SR),modulation transfer function(MTF)values(represen-ted as 10 c·d-1 MTF,20 c·d-1 MTF,and 30 c·d-1MTF,respectively)and cutoff frequencies(MTF cutoff)at the spa-tial frequencies of 10 c·d-1,20 c·d-1 and 30 c·d-1 were measured and recorded using a visual quality analysis system.The data of corneal vertical trefoil(Z3-3),vertical coma(Z3-1),horizontal coma(Z31),horizontal trefoil(Z33),vertical tetrafoil(Z4-4),vertical secondary astigmatism(Z4-2),spherical aberration(Z40),horizontal secondary astigmatism(Z42),horizontal tetrafoil(Z44),and total higher-order aberration(HOA)were measured and recorded using the iTrace aberration meter.The measurement data of patients before surgery,one month after surgery,and three months after sur-gery were compared,and their correlations were analyzed.Results TRDV,RDV-S,RDV-N,RDV 20°-30°,RDV 30°-40°,and RDV 40°-53° around the retina of patients decreased one month and three months after surgery compared with those be-fore surgery,and the differences were statistically significant(all P＜0.001).There were statistically significant differences in OSI,MTF cutoff,and 10 c·d-1 MTF among patients before surgery,one month after surgery,and three months after surgery(all P＜0.05).There were statistically significant differences in corneal Z3-3,Z3-1,Z31,Z33,Z4-4,Z4-2,Z40,Z42,Z44,and HOA among patients before surgery,one month after surgery,and three months after surgery(all P＜0.001).The Pearson correlation analysis results showed that,ΔRDV 0°-10° was positively correlated with ΔZ3-3,ΔZ31,ΔZ4-2,ΔZ40,and ΔZ42(all P＜0.05);ΔRDV 10°-20° was positively correlated with ΔZ4-4 and ΔZ4-2(both P＜0.05);ΔRDV 20°-30° was positively correlated with ΔZ4-4 and ΔZ44(both P＜0.05);ΔTRDV and ΔRDV 40°-53° were negatively correla-ted with ΔHOA(both P＜0.05).ΔRDV-S and ΔZ3-1 were negatively correlated with ΔHOA(both P＜0.05)and positively correlated with ΔZ44(P＜0.05);ΔRDV-N was positively correlated with ΔZ4-4(P＜0.05).Conclusion FS-LASIK can reduce periretinal hyperopic defocus in myopic patients,but it introduces corneal HOA,and there is a certain correlation between the two.

Objective:To investigate the effectiveness of case-based learning (CBL) combined with online teaching in standardized residency training of rheumatology and immunology.Methods:A total of 78 individuals who participated in standardized residency training in Department of Rheumatology and Immunology in our hospital from June 2019 to August 2020 were included and divided into observation group and control group. The individuals in the control group received traditional teaching, and those in the observation group received CBL combined with online teaching. The physicians receiving standardized residency training were evaluated by theoretical examination, clinical operation skill assessment, and instructor rating, and the degree of satisfaction with teaching, degree of satisfaction with teaching methods, and classroom learning atmosphere were also evaluated.Results:The observation group had a theoretical examination score of (94.10±2.01) and a clinical operation skill assessment score of (90.44±1.57), which were significantly higher than those of the control group ( P<0.05), and the observation group had a significantly better instructor rating (89.36±1.33) than the control group ( P<0.05). Compared with the control group, the observation group had significantly higher degree of satisfaction with teaching (3.79±0.41), degree of satisfaction with teaching methods (3.92±0.27), and evaluation of classroom learning atmosphere (3.90±0.31) ( P<0.05). Conclusion:CBL combined with online teaching can help to improve learning efficiency, stimulate the enthusiasm for learning, expand clinical thinking, promote the growth of teaching and learning, and form a virtuous cycle among trainees receiving standardized residency training, which holds promise for further exploration.

Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients.
Rats ; Animals ; Hyperalgesia/metabolism* ; Sleep Deprivation/metabolism* ; Rats, Sprague-Dawley ; Periaqueductal Gray/pathology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Pain, Postoperative/pathology*

Diabetes have been shown to cause progressive neuronal injury with pain and numbness via advanced glycation end-products (AGEs)-induced neuronal cell apoptosis; however, the valuable drug targets for diabetic neuropathy have been poorly reported so far. In this study, we discovered a natural small-molecule schisandrol A (SolA) with significant protective effect against AGEs-induced neuronal cell apoptosis. ATP6V0D1, a major subunit of vacuolar-type ATPase (V-ATPase) in lysosome was identified as a crucial cellular target of SolA. Moreover, SolA allosterically mediated ATP6V0D1 conformation via targeting a unique cysteine 335 residue to activate V-ATPase-dependent lysosomal acidification. Interestingly, SolA-induced lysosome pH downregulation resulted in a mitochondrial-lysosomal crosstalk by selectively promoting mitochondrial BH3-only protein BIM degradation, thereby preserving mitochondrial homeostasis and neuronal cells survival. Collectively, our findings reveal ATP6V0D1 is a valuable pharmacological target for diabetes-associated neuronal injury via controlling lysosomal acidification, and also provide the first small-molecule template allosterically activating V-ATPase for preventing diabetic neuropathy.

OBJECTIVE: To assess the value of copy number variations (CNVs) and chromosomal karyotyping analysis for patients with intellectual disability/developmental delay (ID/DD). METHODS: Chromosomal karyotype analysis was applied to 530 children diagnosed with ID/DD. Single nucleotide polymorphism array (SNP-array) was further applied for 120 children with unknown etiology. RESULTS: Among the 530 children with ID/DD, 104 (19.62%) were detected with chromosomal abnormalities. For the 120 children analyzed by SNP-array, 44 (36.67%) were detected with CNVs, among which 20 were predicted as pathogenic, 6 as likely pathogenic, 10 as variants of unknown significance, 7 as likely benign,and 1 as loss of heterozygosity. CONCLUSION SNP-array can facilitate delineation of the etiology of patients with ID/DD, which may provide a basis for their prognosis, consultation and clinical intervention.
Child ; Chromosome Aberrations ; DNA Copy Number Variations ; Developmental Disabilities/genetics* ; Humans ; Intellectual Disability/genetics* ; Karyotyping

Objective:To evaluate the changes in the blood-cerebrospinal fluid barrier in postoperative delirium rats.Methods:One hundred and forty-seven healthy female Sprague-Dawley rats, aged 3 months, weighing 240-300 g, were divided into 3 groups ( n=49 each) using a random number table method: control group (group C), anesthesia group (group A) and postoperative delirium group (group P). Group C received no treatment.Group A received 2-h anesthesia with 1.4% isoflurane.Group S underwent an exploratory laparotomy under 1.4% isoflurane anesthesia.The behaviors of rats in each group were tested at 24 h before surgery and 6, 9 and 24 h after surgery using buried food test, open field test and Y maze test.Sodium fluorescence was injected through the tail vein at 6, 9 and 24 h after surgery.Then the rats were sacrificed, the choroid plexus (CP) was obtained, and cerebrospinal fluid (CSF) of bilateral cerebral ventricles was collected, and the expression of ZO-1, occludin, claudin1, E-cadherin and VE-cadherin in CP was detected using Western blot.FITC-dextran 10, 40 and 70 kDa was injected through the tail vein at 6 h after surgery, and then CSF was collected for determination of the concentrations of NaFI, 10, 40 and 70 kDa fluorescein isothiocyanate labeled dextran (FITC-dextran) in CSF by fluorescence spectrophotometry.CP was obtained to observe the morphology of choroid plexus epithelial cells (CPECs) of bilateral cerebral ventricles with a transmission electron microscope. Results:Compared with group C and group A, the latency to eat food in buried food test was significantly prolonged, the time of staying at the central region was shortened, the percentage of the number of entries into novel arm and percentage of time of staying at novel arm in Y maze test were decreased, the freezing time in open field test was shortened, the expression of ZO-1, occludin and claudin1 in CP was down-regulated, the concentrations of NaFI and 10 kDa and 40 kDa FITC-dextranin CSF were increased ( P<0.05 or 0.01), the CPECs arranged at random and loose, the microvilli of CPECs were absent, the tight junction was blurred, and the gap became wider in group P. Conclusion:The occurrence of postoperative delirium is related to the change in blood-cerebrospinal fluid barrier.

Objective:To observe the therapeutic effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on insulin resistance, and to investigate the molecular mechanisms in T2DM rats.Methods:The T2DM rats were induced by a high fat and high glucose diet for 10 weeks combined with low-dose streptozocin. Four weeks after infusion of HUC-MSCs via tail vein of the rats, fasting blood glucose, triglycerides, cholesterol were measured. Intraperitoneal glucose tolerance test, intraperitoneal insulin tolerance test and hyperinsulinemic-euglycaemic clamp test were performed to evaluate the islet function and insulin resistance level of rats. The protein expression levels of lipid metabolism signal pathway adenine monophosphate activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC) in liver tissue were detected by western blot.Results:Compared with the T2DM group, HUC-MSCs treatment can significantly reduce fasting blood glucose, triglycerides, total cholesterol levels ( P<0.01), and the values of area under the curve of glucose tolerance and insulin tolerance ( P<0.05) in the T2DM+ HUC-MSCs group. Hyperinsulinemic-euglycaemic clamp test found that compared with the T2DM group, after HUC-MSCs treatment, the glucose infusion rate level was significantly higher in the T2DM+ HUC-MSCs group( P<0.01); Western blot showed that compared with the T2DM group, the ratio of p-AMPK to AMPK and p-ACC to ACC in liver tissues of T2DM+ HUC-MSCs group were significantly increased( P<0.01). Conclusion:Human umbilical cord mesenchymal stem cells treatment may improve lipid metabolism and insulin resistance by activating AMPK/ACC signaling pathways in type 2 diabetic rats.