IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis. However, their involvement in optic neuropathy due to trauma and glaucoma remains unclear. Here, we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina. Deletion of IL-33 or ST2 exacerbated retinal ganglion cell (RGC) loss, retinal thinning, and nerve fiber degeneration following optic nerve (ON) injury. This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33^-/- mice. In vitro, rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors, thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants. Exogenous IL-33 treatment improved RGC survival in Il33^-/- and WT mice after ON injury, but not in ST2^-/- mice. Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.
Animals ; Interleukin-33/genetics* ; Interleukin-1 Receptor-Like 1 Protein/genetics* ; Optic Nerve Injuries/pathology* ; Retinal Ganglion Cells/pathology* ; Astrocytes/pathology* ; Mice ; Mice, Knockout ; Mice, Inbred C57BL ; Neuroprotection/physiology*

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Objective:To investigate the application effect of early awake prone position in mild-to-moderate acute respiratory distress syndrome (ARDS) patients, and analyze the related factors affecting the prone position outcome.Methods:A prospective cohort study was conducted. The mild-to-moderate ARDS patients admitted to the emergency department of Yingshang County People's Hospital from January 2020 to June 2023 were enrolled as the research subjects. According to the results of prone tolerance test, the patients were divided into awake prone position group and non-prone position group. All patients were given high flow nasal cannula (HFNC) according to the standard procedures. The patients in the awake prone position group received prone position treatment within 12 hours after admission, in addition to the standard treatment. This could be performed in several times, at least once a day, and at least 2 hours each time. In order to prolong the prone position as much as possible, the patients were allowed to move or keep a small angle side prone. The changes of oxygenation index (PaO 2/FiO 2) at 0, 24, 48, and 72 hours after admission, the rate of intensive care unit (ICU) transfer, the use rate and use time of non-invasive ventilation (NIV), the total hospital stay, and the daily prone position time and 2-hour ROX index [ratio of pulse oxygen saturation/fraction of inspired oxygen (SpO 2/FiO 2) and respiratory rate (RR)] of prone position patients were recorded. The successful termination of HFNC was defined as the successful prone position, and the failure of prone position was defined as switching to NIV or transferring to ICU. Subgroup analysis was performed, and the binary multivariate Logistic regression analysis was used to screen the influencing factors of the early awake prone position outcome. Results:A total of 107 patients were finally enrolled, with 61 in the awake prone position group and 46 in the non-prone position group. Both groups showed a gradual increase in PaO 2/FiO 2 with prolonged admission time. The PaO 2/FiO 2 at 24 hours after admission in the awake prone position group was significantly higher than that at 0 hour [mmHg (1 mmHg ≈ 0.133 kPa): 191.94±17.86 vs. 179.24±29.27, P < 0.05], while the difference in the non-prone position group was only statistically significant at 72 hours (mmHg: 198.24±17.99 vs. 181.24±16.62, P < 0.05). Furthermore, the PaO 2/FiO 2 at 48 hours and 72 hours after admission in the awake prone position group was significantly higher than that in the non-prone position group. The use rate of NIV in the awake prone position group was significantly lower than that in the non-prone position group [36.1% (22/61) vs. 56.5% (26/46), P < 0.05]; Kaplan-Meier curve analysis further confirmed that the patients in the awake prone position group used NIV later, and the cumulative rate of NIV usage was significantly lower than that in the non-prone position group (Log-Rank test: χ2 = 5.402, P = 0.020). Compared with the non-prone position group, the ICU transfer rate in the awake prone position group was significantly lowered [11.5% (7/61) vs. 28.3% (13/46), P < 0.05], and the HFNC time, NIV time, and total hospital stay were significantly shortened [HFNC time (days): 5.71±1.45 vs. 7.24±3.36, NIV time (days): 3.27±1.28 vs. 4.40±1.47, total hospital stay (days): 11 (7, 13) vs. 14 (10, 19), all P < 0.05]. Of the 61 patients who underwent awake prone positioning, 39 were successful, and 22 failed. Compared with the successful group, the patients in the failure group had a higher body mass index [BMI (kg/m 2): 26.61±4.70 vs. 22.91±5.50, P < 0.05], lower PaO 2/FiO 2, proportion of asymptomatic hypoxemia and 2-hour ROX index of prone position [PaO 2/FiO 2 (mmHg): 163.73±24.73 vs. 185.69±28.87, asymptomatic hypoxemia proportion: 18.2% (4/22) vs. 46.2% (18/39), 2-hour ROX index of prone position: 5.75±1.18 vs. 7.21±1.45, all P < 0.05], and shorter daily prone positioning time (hours: 5.87±2.85 vs. 8.05±1.99, P < 0.05). Binary multivariate Logistic regression analysis showed that all these factors were influencing factors for the outcome of awake prone positioning (all P < 0.05), among which BMI [odds ratio ( OR) = 1.447, 95% confidence interval (95% CI) was 1.105-2.063] and non-asymptomatic hypoxemia ( OR = 13.274, 95% CI was 1.548-117.390) were risk factors for failure of prone position, while PaO 2/FiO 2 ( OR = 0.831, 95% CI was 0.770-0.907), daily prone positioning time ( OR = 0.482, 95% CI was 0.236-0.924), and 2-hour ROX index of prone position ( OR = 0.381, 95% CI was 0.169-0.861) were protective factors. Conclusions:Early awake prone positioning in patients with mild-to-moderate ARDS supported by HFNC is safe and feasible, reducing the use rate and duration of NIV, lowering the ICU transfer rate, and shortening the hospital stay. High BMI and non-asymptomatic hypoxemia are risk factors for failed prone position, while higher PaO 2/FiO 2 and the ROX index within 2 hours of prone position (the patient's good response to prone position), and prolonged daily prone position can improve the success rate of prone position.

Objective To investigate the effect of transcranial alternating current stimulation(tACS)on cerebral blood flow(CBF)in patients with Alzheimer's disease(AD).Methods A ret-rospective study was conducted on 21 mild AD patients admitted in our hospital from September 2019 to April 2022.All of them received tACS treatment for 3 weeks.Mini-mental state examina-tion(MMSE),auditory verbal learning test(AVLT)and MRI were applied to obtain the data at baseline(T0),the end of the treatment(T1)and in three months after treatment(T2).Z-trans-form CBF(zCBF)was performed to reduce individual variability.The changes in MMSE and AVLT scores,as well as brain zCBF and CBF values before and after tACS treatment were ana-lyzed.Spearman correlation analysis was used to examine the relationship of zCBF and CBF with cognitive scores.Results In the AD patients,their MMSE score was significantly increased at T1 than at T0[22.00(20.00,25.00)vs 20.00(18.00,21.50),P＜0.01].Based on voxel analysis,the AD patients exhibited significantly increased zCBF in the bilateral frontal and temporal cortex at T1,and in the right frontal and temporal cortex at T2 when compared with the levels at T0(P＜0.05).The most pronounced increase in zCBF was observed in the right insular.Based on region of inter-est analysis,increased zCBF and CBF in the right frontal and temporal cortex at T1 were observed(P＜0.05).There was a positive correlation between the change of CBF in the right frontal cortex and AVLT-recognition recall at T1(r=0.617,P=0.005)and between the change of CBF in the left frontal cortex and MMSE at T2(r=0.596,P=0.012).Conclusion MRI 3D-ASL can objec-tively evaluate the changes of CBF in AD patients after tACS treatment,and it provides a reliable imaging marker for evaluating the efficacy of tACS.

Objective: To investigate the awareness of hepatitis C prevention and control knowledge and its influencing factors among female sex workers (FSWs) in Jiaxing City, Zhejiang Province. Methods: According to the HIV/AIDS Sentinel Surveillance Plan, FSWs at ages of 15 to 65 years monitored by the national AIDS surveillance sentinel in Jiaxing City were recruited, and demographic information, awareness of hepatitis C prevention and control knowledge and related behaviors were collected by questionnaire surveys. Factors affecting the awareness of hepatitis C prevention and control knowledge were identified by a multivariable logistic regression model. Results: A total of 430 questionnaires were allocated, and 412 were valid, with an effective rate of 95.81%. The respondents had a mean age of (28.58±4.93) years, and included 258 unmarried FSWs (62.62%), 344 with registered residence outside Zhejiang Province (83.50%), 212 with junior high school education or below (51.46%) and 243 from high-end entertainment places (58.98%). The overall awareness of hepatitis C prevention and control knowledge among FSWs was 20.39%, and the awareness of "Transfusion of blood containing hepatitis C virus may acquire hepatitis C" (38.83%) and the awareness of "tattooing, eyebrow tattooing and ear piercing in streets or small shops may infect hepatitis C" (38.11%) were relatively low. Multivariable logistic regression analysis identified marital status (divorced or widowed, OR=0.161, 95%CI: 0.054-0.482), educational level (high school or technical secondary school, OR=2.568, 95%CI: 1.446-4.560; junior college or above, OR=6.110, 95%CI: 2.658 -14.045) and grade of entertainment places (high-end entertainment places, OR=2.756, 95%CI: 1.525-4.982) as factors affecting the awareness of hepatitis C prevention and control knowledge among FSWs. Conclusion FSWs in Jiaxing City have a low awareness of hepatitis C prevention and control knowledge, especially lacking of knowledge about the transmission routes and prognosis of hepatitis C.

Diabetic gastroparesis （DGP） is a common diabetic neuropathy that affects the normal function of gastric motility and emptying. Clinically， it often manifests as abdominal distension， nausea and vomiting， early satiety， dyspepsia， etc. The pathogenesis of DGP is multifactorial， closely related to many factors， such as chronic hyperglycemia， neuropathy， autonomic nervous system disorders， inflammation， and oxidative stress. These factors can interact with each other， leading to delayed gastric emptying and the occurrence of related symptoms. Traditional Chinese medicine （TCM） has significant advantages in the prevention and treatment of DGP， including a long history， remarkable efficacy， individualized treatment， diverse therapeutic formulations， and improvement in the quality of life. Additionally， TCM is known for its low adverse reactions， good tolerance， and multi-targeted effects， making it an important approach in the management of DGP. Previous research has found that the main mechanisms of Chinese medicine in the prevention and treatment of DGP include the regulation of gastrointestinal hormones， inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and modulation of related signaling pathways such as stem cell factor （SCF）/cellular growth factor receptor （c-Kit）， adenosine monophosphate-activated protein kinase （AMPK）， Ras homologous genome member A （RhoA）/Rho-associated coiled-coil forming kinase （ROCK）. This article primarily summarized the research progress on Chinese medicine in preventing and treating DGP through the inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and regulation of related signaling pathways， aiming to provide a reference and basis for further research on the application value of Chinese medicine in the prevention and treatment of DGP.

Flubromazolam(Flub)is a novel psychoactive substance of benzodiazepines and the mechanism underlying its addiction still remains elusive.This study investigated the reward effect of Flub using conditioned place preference(CPP)mouse model.The neuronal activity was evaluated by c-Fos expression,and the neural circuit was tracked by virus tracing.This study also investigated the regulatory effect of neural circuits on Flub-induced reward effects through chemogenetic approach.The results showed that,at the dose of 3 mg/kg,Flub significantly increased CPP score and c-Fos expression in dopaminergic(DA)neurons of ventral tegmental area(VTA).Inhibition of VTA dopaminergic neuron activity dramatically decreased Flub-induced CPP score.Virus tracing verified GABAergic neuronal projection of medial rostrum tegmental nucleus(RMTg)to VTA dopaminergic neurons.Activation of RMTgGABA→VTADA circuit or blockade of benzodiazepine receptors(BZR)in RMTg significantly decreased Flub-induced CPP score.These results indicate that Flub produced reward effect via BZR-mediated RMTgGABA→VTADA circuit.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.