Diabetic retinopathy(DR)is one of the most common and severe microvascular complications in diabetic patients and has become one of the leading causes of blindness worldwide. With the continuous rise in the prevalence of diabetes, in-depth exploration of the pathogenesis of DR and effective intervention measures is of great clinical significance. The mechanistic target of rapamycin(mTOR), as a protein kinase, is widely involved in cellular processes such as growth, metabolism, and autophagy. Research indicates that the mTOR signaling pathway plays a crucial regulatory role in the pathological progression of DR, and its abnormal activity can disrupt retinal cell autophagy function, thereby accelerating cellular damage and disease progression. Autophagy, as an important regulatory mechanism for cellular homeostasis, maintains cellular functional balance by clearing damaged organelles and protein aggregates. This article provides a systematic review of the structural and functional aspects of the mTOR signaling pathway, the molecular regulatory mechanisms of autophagy, and their roles in retinal pathological changes. By summarizing current research findings, the article aims to clarify the key regulatory role of the mTOR-autophagy axis in DR, providing theoretical support for elucidating the molecular pathogenesis of DR and offering potential targets and research directions for developing novel targeted therapeutic strategies, thereby holding significant scientific and clinical value.

OBJECTIVE: To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO). METHODS: A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed. RESULTS: A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×10⁹/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups. CONCLUSIONS Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans ; Colistin/therapeutic use* ; Retrospective Studies ; Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Male ; Female ; Middle Aged ; Gram-Negative Bacteria/drug effects* ; Aged ; Treatment Outcome ; Respiratory Tract Infections/drug therapy*

Objective To explore the correlation between speech fluency and diadochokinetic rate in children aged 7～11 years with cochlear implant.Methods Speech samples were collected from 62 children aged 7～11 years with cochlear implant using language retelling task and diadochokinetic rate test task.Their speech rate,articulation rate,syllable duration and pause duration were analyzed.The data were input into ICF converter to obtain the im-pairment limit of each parameter and analyze the speech fluency and diadochokinetic rate characteristics.Partial cor-relation analysis was performed for speech rate,articulation rate,syllable duration and pause duration by two tasks.Results ① For children with cochlear implant,the mean ICF impairment limit of diadochokinetic rate was 1.3± 0.1,the mean ICF impairment limit of fluency in retelling was 1.0±0.3,with various degree of impairment in both tasks.② There was a moderate or low correlation between speech rate,articulation rate,syllable duration in retell-ing task and those in diadochokinetic rate task(0.3＜|r |≤0.8).There was a low correlation between pause dura-tion in retelling task and speech rate and pause duration in diadochokinetic rate task(0.3＜|r |≤0.5).Conclusion The speech fluency and diadochokinetic rate of children aged 7～11 years with cochlear implant is underdeveloped,and the poor articulation movement ability limits their development of speech fluency.

Objective:To study the effects of fluoride on apoptosis and oxidative stress levels of spinal cord nerve cells in rats.Methods:A total of 54 6-week-old Sprague-Dawley female rats, weighing 150 - 200 g, were selected and fed for 1 week. They were divided into a control group [given deionized water containing 0 mg/L sodium fluoride (NaF)], a low fluoride group (given deionized water containing 50 mg/L NaF), and a high fluoride group (given deionized water containing 100 mg/L NaF) using a random number table method, with 18 rats in each group. All groups received standard feed. After 4, 8, and 12 weeks of fluoride exposure, six rats were selected from each group to observe the occurrence of dental fluorosis, and the motor function of hind limbs in rats was evaluated based on the Basso-Beattie-Bresnahan (BBB) score. Then the rats were anesthetized with 5% chloral hydrate via intraperitoneal injection and euthanized by cardiac puncture. Spinal cord tissue of the rats was collected to detect the activities of oxidative stress factors such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as the contents of malondialdehyde (MDA) and catalase (CAT). After 12 weeks of fluoride exposure, morphologic changes in rat spinal cord neurons were observed using Nissl staining, and apoptosis of spinal cord nerve cells was detected using the TdT mediated dUTP nick end labeling (TUNEL) cell apoptosis detection kit. The Western blotting was used to detect the expression of B-lymphoblastoma-2 (Bcl-2) gene related X protein (Bax), Bcl-2 promoter (Bad), and Bcl-2 protein in rat spinal cord tissue; immunofluorescence staining was used to observe the expression of Bax and Bcl-2 protein in spinal cord neurons.Results:After 12 weeks of fluoride exposure, rats in both the low fluoride and high fluoride groups developed varying degrees of dental fluorosis; the differences of BBB scores of rats in the control, low fluoride, and high fluoride groups were statistically significant ( F = 14.09, P < 0.001). The differences of SOD [(124.04 ± 4.87), (96.66 ± 15.01), (91.12 ± 15.87) U/mg prot] and GSH-Px activitives [(561.92 ± 59.65), (456.83 ± 29.51), (385.07 ± 74.87) U/mg prot], MDA [(9.96 ± 1.50), (16.64 ± 2.05), (20.80 ± 3.37) nmol/mg prot] and CAT contents [(8.97 ± 1.05), (6.39 ± 0.97), (6.42 ± 0.83) nmol/mg prot] among the control, low fluoride, and high fluoride groups were statistically significant ( F = 11.17, 14.19, 30.12, 14.52, P < 0.05). Among them, the SOD, GSH-Px activities, and CAT content in the low fluoride and high fluoride groups were lower than those in the control group, while the MDA content was higher than that in the control group ( P < 0.05). The GSH-Px activity in the high fluoride group was lower than that in the low fluoride group, and MDA content was higher than that in the low fluoride group ( P < 0.05). The intact neuronal structures and clear visible nuclei were seen, and Nissl bodies were uniformly stained in the spinal cord neurons of the control group rats, with more numbers, and no apoptotic cells were observed; the staining of Nissl bodies in the spinal cord neurons of rats was uneven in the low fluoride and high fluoride groups, with fewer numbers, and more apoptotic cells. There were statistically significant differences in the apoptosis rate of spinal cord nerve cells and the expression levels of Bax, Bad, and Bcl-2 protein in the spinal cord tissues of rats in the control, low fluoride, and high fluoride groups ( F = 272.81, 35.53, 17.57, 92.50, P < 0.05). The results of immunofluorescence staining showed that there were statistically significant differences in the fluorescent intensity of Bax and Bcl-2 proteins in the spinal cord neurons of rats in the control, low fluoride, and high fluoride groups ( F = 12.67, 22.14, P < 0.05). Conclusion:Chronic fluorosis induces a decrease in antioxidant enzyme activity, an increase in lipid peroxidation levels, and an increase in neuronal apoptosis in the spinal cord of rats.

[摘 要] 目的：探讨溶瘤新城疫病毒（NDV）对IL-6诱导的人胶质母细胞瘤U87MG细胞增殖、迁移和侵袭的作用及其可能的机制。方法：将U87MG细胞分为对照组、IL-6组、NDV组、NDV+IL-6组，其中IL-6组与NDV+IL-6组用75 ng/mL IL-6预处理1 h，其余组用DMEM预处理1 h，后分别用DMEM、75 ng/mL IL-6、1 HU NDV、1 HU NDV+75 ng/mL IL-6处理24 h。MTT法、细胞划痕实验和Transwell侵袭实验分别检测IL-6、NDV对U87MG细胞增殖、迁移和侵袭的影响，WB法检测各组细胞JAK2、p-JAK2、STAT3、p-STAT3和MMP2蛋白的表达水平。结果：与对照组相比，IL-6组细胞迁移率显著升高（P<0.05），侵袭细胞数目显著增多（P<0.01）；与IL-6组相比，NDV+IL-6组U87MG细胞增殖率显著降低（P<0.05），细胞迁移率和侵袭细胞数目均显著降低（均P<0.01）。WB实验结果显示，与对照组相比，IL-6组p-STAT3/STAT3比值显著升高（P<0.01），NDV组p-JAK2/JAK2、p-STAT3/STAT3比值显著降低（P<0.05，P<0.01），MMP-2蛋白表达量显著降低（P<0.01）；与IL-6组相比，NDV+IL-6组p-STAT3/STAT3比值、MMP-2蛋白表达量均显著降低（均P<0.05）。结论：NDV能抑制IL-6对人脑胶质瘤U87MG细胞迁移和侵袭的诱导作用，其机制可能与JAK2/STAT3信号通路的参与调控有关。

Retiform hemangioendothelioma (RH) is a rare vasogenic malignancy with a high local recurrence rate and rare distant metastasis. Hepatic RH in infants is extremely rare. Here we report a case of liver RH in a 7-month-old infant.

Objective:To assess the prevalence and type of tissue prolapse (TP) occurring after endovascular treatment (ET), investigate the association between TP types and plaque morphological characteristics before ET, and observe in-stent neointimal hyperplasia (NIH) using optical coherence tomography (OCT).Methods:Patients who underwent carotid artery stenting and received pre- and post-ET OCT assessment at Jinling Hospital between July 2018 and December 2019 were collected. Baseline plaque characteristics and TP features were evaluated using OCT. The TPs were classified into two categories: smooth TP (STP) and irregular and/or high attenuated TP (I/HTP). The association between I/HTP and plaque characteristics was analyzed, while NIH feature was also summarized.Results:A total of 29 patients were included in the study, of whom 23 patients (79.3%) presented with TP. Among these 23 patients, 9 were classified as I/HTP and 14 were classified as STP. Compared with STP, I/HTP was more commonly observed in lipid-rich plaques (7/9 vs 2/14, P=0.007), and lesions with cap rupture (7/9 vs 4/14, P=0.036). Additionally, the longitudinal length of TP appeared to be longer in cases with I/HTP compared to those with STP [3.0 (1.5, 4.6) mm vs 1.1 (0.7, 3.2) mm, Z=1.294, P=0.201]. Six patients underwent OCT follow-up for a mean duration of 6.7 months, of whom 3 patients with I/HTP showed severe heterogeneous NIH (50.1%-61.8%), while 1 patient with STP and 2 patients without TP only demonstrated mild NIH. Conclusions:The study observed that I/HTP was commonly found in plaques with larger lipid core and/or cap rupture, and suggested a potential relationship between I/HTP and NIH. These preliminary findings obtained from a limited sample should be verified by prospective large-scale studies.

Brucellosis is a zoonotic disease caused by Brucella. Its typical clinical manifestations include fever, chills, fatigue, bone and muscle pain, etc. Brucellosis can affect multiple organs and tissues, of which spine is the most common affected part, forming Brucella spondylitis. Due to the clinical manifestations and imaging characteristics of infected individuals being similar to other spinal diseases, it is easy to cause misdiagnosis, missed diagnosis, and mistreatment. This article reviews the latest research progress in clinical manifestations, imaging examination, diagnosis, differential diagnosis, and treatment of Brucella spondylitis both domestically and internationally, in order to provide reference for the diagnosis and treatment of Brucella spondylitis.

Objective:To explore the changes of mitophagy- and apoptosis-related protein expressions after spinal cord injury in rats and its related mechanism.Methods:Ninety-six healthy female SD rats were divided into sham surgery group ( n=48) and spinal cord injury group ( n=48) according to the random number table. Each group was divided into six time points of 1, 3, 7, 14, 21 and 28 days with 8 rats at each time point. In the sham surgery group, the T 8-9 spinous processes and vertebral plates were removed without damage to the spinal cord; in the spinal cord injury group, the spinal cord injury model was established using Allen′s method. At each post-injury time point in two groups, BBB score was used to evaluate the motor function of the rats; HE staining was used to observe the histopathological changes of the spinal cord; immunofluorescence was used to observe the co-localized positive cells of the voltage-dependent anion channel protein 1 (VDAC1) with microtubule-associated protein 1 light chain 3 (LC3) II, E3 ubiquitin ligase (Parkin), and polyubiquitin-binding protein (p62); Western blotting was used to observe expressions of the mitochondrial LC3 II/LC3 I, cytoplasmic Parkin, mitochondrial Parkin, cytoplasmic p62, mitochondrial p62, cytoplasmic apoptotic proteins (Bax), mitochondrial Bax, cytoplasmic cytochrome C (Cyt C), and mitochondrial Cyt C. Results:(1) Compared with the sham surgery group [(21.00±0.00)points at all time points], the BBB scores in the spinal cord injury group were (0.94±0.50)points, (1.69±0.70)points, (4.13±0.99)points, (11.81±1.03)points, (15.06±1.12)points and (18.38±0.83)points at 1, 3, 7, 14, 21 and 28 days after injury, respectively ( P<0.01). (2) Compared with the sham surgery group, the structure in the spinal cord injury group was significantly disrupted at 1 and 3 days after injury, when a large number of hemorrhagic foci, inflammatory cell infiltration, neuronal swelling, and cavity formation were observed. At 7 and 14 days after injury, the number of hemorrhagic foci was markedly reduced compared with the earlier period, when swollen neuronal cytosols, inflammatory cell infiltration and a large number of cavities were found. At 21 and 28 days after injury, a large number of cells were seen to be involved in the repair and the arrangement of cells was disorganized. (3) Compared with the sham surgery group, the number of co-localized positive cells of VDAC1 with LC3 II, Parkin and p62 separately in the spinal cord injury group, markedly increased at 1 and 3 days after surgery, and gradually decreased after that. (4) In the sham surgery group and at 1, 3, 7, 14, 21 and 28 days after injury in the spinal cord injury group, the mitochondrial LC3 II/LC3 I expression levels were 0.56±0.05, 1.00±0.05, 1.19±0.11, 0.86±0.05, 0.80±0.08, 0.66±0.13 and 0.51±0.11, respectively; the cytoplasmic Parkin expression levels were 0.80±0.13, 0.47±0.08, 0.29±0.06, 0.57±0.07, 0.70±0.05, 0.97±0.09 and 0.88±0.12, respectively; the mitochondrial Parkin expression levels were 0.67±0.09, 1.07±0.18, 1.27±0.15, 0.82±0.12, 0.59±0.09, 0.53±0.13 and 0.57±0.14, respectively; the cytoplasmic p62 expression levels were 1.25±0.08, 1.04±0.04, 0.94±0.05, 1.09±0.05, 1.19±0.06, 1.20±0.04 and 1.27±0.05, respectively; the mitochondrial p62 expression levels were 0.61±0.06, 0.88±0.07, 1.09±0.09, 0.98±0.07, 0.70±0.08, 0.68±0.08 and 0.60±0.09, respectively; the cytoplasmic Bax expression levels were 0.92±0.08, 0.67±0.07, 0.36±0.08, 0.48±0.08, 0.69±0.06, 0.88±0.11 and 0.94±0.08, respectively; the mitochondrial Bax expression levels were 0.57±0.04, 0.74±0.04, 0.91±0.05, 0.76±0.05, 0.63±0.08, 0.61±0.05 and 0.57±0.05, respectively; the cytoplasmic Cyt C expression levels were 0.28±0.05, 0.81±0.07, 1.12±0.08, 0.64±0.07, 0.67±0.13, 0.60±0.11 and 0.37±0.06, respectively; and the mitochondrial Cyt C expression levels were 1.02±0.07, 0.91±0.14, 0.37±0.07, 0.73±0.06, 0.91±0.11, 0.95±0.13 and 1.10±0.15, respectively. Compared with the sham surgery group, in the spinal cord injury group mitochondrial LC3II/LC3I had the highest expression level at 3 days after injury; cytoplasmic Parkin had the lowest expression level at 3 days after injury; mitochondrial Parkin had the highest expression level at 3 days after injury; cytoplasmic p62 had the lowest expression level at 3 days after injury; mitochondrial p62 had the highest expression level at 3 days after injury; cytoplasmic Bax had the lowest expression level at 3 days after injury; mitochondrial Bax had the highest expression level at 3 days after injury; cytoplasmic Cyt C had the highest expression level at 3 days after injury; and mitochondrial Cyt C had the lowest expression level at 3 days after injury. Conclusion:Mitochondrial autophagy and apoptosis are enhanced after spinal cord injury in rats, and the potential mechanism may be associated with the transfer of Parkin and P62 from the cytoplasm to the damaged mitochondria for enhanced mitophagy and the release of a large amount of Cyt C from the mitochondria caused by the transfer of Bax from the cytoplasm to the damaged mitochondria for enhanced apoptosis.