ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To investigate the effect of daratumumab, lenalidomide and dexamethasone on quality of life in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). METHODS: The clinical data of 93 TIE NDMM patients in our hospital from January 2020 to December 2022 were retrospectively analyzed. The patients were divided into D-Rd group (48 cases) and Rd group (45 cases) according to treatment regimen. The patients in Rd group were treated with lenalidomide and dexamethasone, while those in D-Rd group were treated with daratumumab on the basis of Rd group. The QLQ-C30 and EQ-5D VAS scores of the two groups were compared at baseline and after 3, 6 and 12 treatment cycles. The last follow-up date was June 30, 2023, and overall survival (OS) was compared between the two groups. RESULTS: The median follow-up period in the D-Rd group was 21 (7-38) months, and the median OS was 34 months, while that in the Rd group was 16 (5-35) months, and the median OS was 28 months. There was significant difference in OS between the two groups ( P <0.05). After 3, 6 and 12 treatment cycles, the QLQ-C30 score and EQ-5D VAS score of the two groups were significantly improved (all P <0.05). After 3 and 12 treatment cycles, the QLQ-C30 score and EQ-5D VAS score of D-Rd group were significantly higher than those of Rd group (all P <0.05). There were no significant differences in the improvement of QLQ-C30 GHS and pain scores between the two groups of patients with age <75 years and ECOG 0-1 score after 3, 6 and 12 treatment cycles (P >0.05). In D-Rd group of patients with age≥75 years, the improvement of QLQ-C30 GHS scores after 3 and 12 treatment cycles and QLQ-C30 pain scores after 3, 6 and 12 treatment cycles was significantly superior to that in Rd group (all P <0.05). In D-Rd group of patients with ECOG 2 scores, the improvement of QLQ-C30 GHS and pain scores after 3, 6 and 12 treatment cycles was significantly superior to that in Rd group (all P <0.05). CONCLUSION Daratumumab, lenalidomide, and dexamethasone can significantly improve OS in TIE NDMM patients without decrease of quality of life, especially in those with age≥75 years or ECOG 2 scores.
Humans ; Multiple Myeloma/drug therapy* ; Lenalidomide/therapeutic use* ; Quality of Life ; Dexamethasone/therapeutic use* ; Retrospective Studies ; Antibodies, Monoclonal/therapeutic use* ; Female ; Male ; Middle Aged ; Aged ; Stem Cell Transplantation

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective To investigate the clinical efficacy and safety of Yiqi Huatan Tongluo Prescription(mainly composed of Fici Simplicissimae Radix,Notoginseng Radix et Rhizoma,Pinelliae Rhizoma Praeparatum,Poria,Nelumbinis Folium,and Glycyrrhizae Radix et Rhizoma,etc.)combined with drug-coated balloon(DCB)in the treatment of coronary heart disease(CHD)and to observe its effect on low-shear related serological indicators.Methods A total of 106 patients with CHD of qi deficiency and phlegm stasis obstructing collateral type who were scheduled to undergo percutaneous coronary intervention were randomly divided into a treatment group and a control group,with 53 cases in each group.The control group was treated with drug-eluting stent implantation,and the treatment group was treated with DCB.After the operation,the control group was given conventional antiplatelet aggregation drugs,and the treatment group was given oral administration of Yiqi Huatan Tongluo Prescription.The medication for the two groups lasted for 12 weeks.The changes in the serum levels of monocyte chemoattractant protein 1(MCP-1),interleukin 1 β(IL-1β)and vascular endothelial growth factor(VEGF)in the two groups were observed before and after treatment.Moreover,the traditional Chinese medicine(TCM)syndrome efficacy after treatment and the incidence of adverse events one year after operation were compared between the two groups.Results(1)After 12 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 88.68％(47/53),and that of the control group was 75.47％(40/53).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.05).(2)The analysis of indicators related to endothelial dysfunction in the blood flow with low shear stress showed that after treatment,the levels of serum MCP-1,IL-1βand VEGF in the control group presented no obvious changes(P＞0.05),but the serum levels of MCP-1 and IL-1β in the treatment group were significantly lowered compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum MCP-1,IL-1β and VEGF levels in the treatment group was significantly superior to that in the control group(P＜0.05).(3)The one-year follow-up after the operation showed that the total incidence of adverse events in the treatment group was 18.87％(10/53),and that in the control group was 20.75％(11/53).There was no significant difference between the two groups(P＞0.05).Conclusion Yiqi Huatan Tongluo Prescription combined with DCB has definite action on the targets related to endothelial dysfunction in coronary blood flow with low shear stress,which is conducive to reducing inflammatory response,improving the symptoms of angina pectoris and enhancing clinical efficacy.The incidence of adverse events did not increase one year after operation,indicating good safety and effectiveness.

AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P＜0.01);decreased retinal thickness(P＜0.01);decreased retinal blood perfusion(P＜0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P＜0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P＜0.01);increased retinal blood flow(P＜0.01);increased amplitudes of ERG a wave and b wave(P＜0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P＜0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

A 6-month primary care quality improvement (QI) project was conducted for 63 general practice residents at Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from November 2021 to April 2022. The effectiveness of the QI project on the post competency of general practice residents was comprehensively assessed by three dimensions: self-satisfaction, objective evaluation and teacher-evaluation. The overall satisfaction score of general practice residents was significantly increased after the implementation of QI project((3.83±0.67) vs. (3.41±0.63), t=3.35, P=0.009). The total score of objective assessment was increased from (73.48±8.04) before the project implementation to (78.14±5.24) after the implementation ( t=3.37, P=0.001). The total score of training effectiveness significantly increased from (57.57±11.84) before the project implementation to (79.27±8.40) after the implementation ( t=30.07, P<0.001). The results indicate that the primary care QI project can improve the post competency of general practice residents, and also improve the self-satisfaction of residents for active learning and participation in the training.