Objective:To study the clinical characteristics and risk factors of nephrocalcinosis in preterm infants.Methods:From March 2021 to August 2021, all preterm infants admitted to NICU of our hospital were retrospectively analyzed. The infants were assigned into nephrocalcinosis group and non-nephrocalcinosis group according to urinary tract ultrasound. Clinical data including gestational age, birth weight(BW), nutritional support strategy and complications were reviewed.Results:A total of 40 preterm infants (<34 weeks) were enrolled. 9 cases were in the nephrocalcinosis group and 31 cases in the non-nephrocalcinosis group. The nephrocalcinosis group had lower BW[(1 167±214) g vs.(1 586±215) g], higher calcium [6.9 (5.1, 8.7) g vs.3.3 (2.1, 6.8) g] and vitamin D intake [3.2(2.5, 4.2)×10 4U vs.1.7(1.1, 3.2)×10 4U] during hospitalization. No significant differences existed between the two groups on the following items:blood calcium and phosphate, 25-hydroxyvitamin D, feeding strategy, time to reach full enteral feeding(TFF), furosemide dosage and respiratory support duration ( P>0.05). In the nephrocalcinosis group, the median age of diagnosing nephrocalcinosis was 40.0(30.0, 52.5)d after birth. 5 cases showed bilateral nephrocalcinosis. 5 cases in the nephrocalcinosis group received renal tubule function examination,4 cases had increased urine β2 microglobulin and 2 cases had increased urine α1 microglobulin. 7 cases had elevated urine calcium in the nephrocalcinosis group. Follow-up showed that nephrocalcinosis disappeared 3-9 months after birth. Conclusions:BW, total calcium and vitamin D intake are risk factors for nephrocalcinosis in preterm infants. Increased urine β2 microglobulin and calcium levels are common co-morbidities in preterm infants with nephrocalcinosis.

Objective:To evaluate the effect of sleep deprivation on the expression of sirtuin 6 (SIRT6) in the cerebellum of immature mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 4 weeks, weighing 14-16 g, were divided into 2 groups ( n=25 each) using a random number table method: control group (Con group) and sleep deprivation group (SD group). The chronic sleep deprivation model was prepared by using the multi-platform water environment method, with 20 h of sleep deprivation per day for 10 consecutive days. After sleep deprivation, a balance beam experiment was performed to test the balance and coordination ability of mice. The mice were sacrificed after anesthesia and cerebellar lobular IV-VI (4-6 cb) tissues were taken for microscopic examination of the ultrastructure (with a transmission electron microscope) and for determination of the dendritic spine density of cerebellar 4-6cb Purkinje neurons (by Golgi staining), co-expression of SIRT6 and Calbindin D-28k (CbD-28k) and expression of glucose transporter Glut3 of cerebellar 4-6cb (by immunofluorescence staining). Results:Compared with group Con, the duration of passage through the balance beam was significantly prolonged, and the number of posterior foot slips was increased, the synaptic gap of cerebellar 4-6cb neurons was increased, the thickness of postsynaptic density was increased, the density of dendritic spines of Purkinje cells and the number of positive cells co-expressing SIRT6 and CbD-28k were decreased, and the expression of Glut3 was down-regulated in group SD ( P<0.05). Conclusions:The mechanism by which sleep deprivation decreases the abilities of balance and coordination is related to down-regulating SIRT6 expression in cerebellar Purkinje cells and decreasing neuronal glucose metabolism, thus damaging the synaptic plasticity of cerebellum in immature mice.

With the process of China’s aging population intensifying， palliative care， as an important guarantee for improving the quality of life of terminally ill patients， is receiving more and more social attention， and the demand is constantly increasing. Palliative care needs versatile professionals， and general education can enhance people’s awareness and understanding of it， enabling more people to understand， accept， and participate in palliative care. With the advancement of knowledge and technology in palliative care， the traditional cramming education models are no longer able to meet the actual needs. Therefore， there is an urgent need to innovate palliative care education strategies. By analyzing the current problems in the general education of palliative care in China， this paper proposed thoughts and suggestions for general and innovative education of palliative care in several aspects， such as establishing general and innovative education systems and evaluation systems of palliative care， diversifying educational contents and methods， strengthening medical staffs training， promoting diversified student groups， and strengthening the popularization of palliative care knowledge among the public.

Objective To analyze the magnetic resonance images (MRI) of patients with spinal epidural lipomatosis (SEL) in high-altitude areas and to determine the optimal cut-off value for diagnosis with epidural fat thickness. Methods This retrospective study included patients who underwent lumbosacral MRI examination for lumbosacral pain in Ping’an District Hospital of Traditional Chinese Medicine, Haidong City, China from January 1, 2021 to December 31, 2022. The epidural fat thickness in vertebral segments T12/L1 to L5/S1 was compared between the SEL group and the non-SEL group. The diagnostic efficacy with different cut-off values at each vertebral segment was evaluated. Between-group comparisons were performed using the t-test, Mann-Whitney U test, chi-square test, or modified chi-square test. The area under the receiver operating characteristic (AUC) was used to evaluate the diagnostic efficiency. The DeLong test was used to compare AUC between the two groups. Results A total of 370 patients were included (60 in the SEL group and 310 in the non-SEL group). There were no significant differences in age, sex, height, body weight, and body mass index between the two groups (all P > 0.05). At different vertebral segments, the epidural fat thickness was significantly higher in the SEL group than in the non-SEL group (all P < 0.05). The cut-off values for SEL diagnosis with epidural fat thickness in segments T12/L1 to L5/S1 were 2.23, 4.25, 4.85, 5.57, 7.21, and 8 mm, respectively. The AUC of MRI SEL diagnosis with epidural fat thickness in segment L5/S1 was the highest (0.945, 95% confidence interval [CI]: 0.916-0.966, P < 0.001). SEL diagnosis with epidural fat thickness > 8 mm in segment L5/S1 was the most accurate, with an AUC of 0.931 (95% CI: 0.901-0.955, P < 0.001), a sensitivity of 95.0%, and a specificity of 91.3%; this AUC was significantly higher than those of diagnosis with other cut-off values (all P < 0.05). Conclusion SEL patients have significantly increased epidural fat in the spinal canal. Epidural fat thickness > 8 mm in segment L5/S1 can be used for diagnosis of SEL with improved efficiency and accuracy.

ObjectiveTo systematically explore the underlying mechanisms of Huashi Baidu prescription （HBP） against myocardial injury through a multidimensional network analysis of "transcriptome-putative target-phenotype gene". MethodPutative targets of compounds in HBP were predicted using the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0，http：//www.tcmip.cn/ETCM2/front/） and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0，http：//www.tcmip.cn/TCMIP/index.php/Home/Login/login.html）. Clinical predominant symptom phenotypes for HBP against coronavirus disease 2019 （COVID-19） were collected from CNKI and PubMed databases， while clinical side effects of doxorubicin were gathered from the CTD database. Phenotype-related genes were collected from the HPO database and SoFDA data platform （http：//www.tcmip.cn/Syndrome/front/#/）. An interaction network of "transcriptome-putative target-phenotype gene" was constructed. Key nodes were identified through topological feature calculations， and functional enrichment analysis was conducted to explain the underlying mechanism. Pharmacodynamic evaluation and mechanism verification were performed using a doxorubicin-induced myocardial injury mouse model. Sixty-five SPF-grade C57BL/6J male mice were randomly divided into a control group， a doxorubicin model group， and low-， medium-， and high-dose HBP groups （HBP-L/M/H）， with 13 mice per group. Histopathological severity was assessed using hematoxylin-eosin （HE） and Masson staining. Fibrosis markers were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and protein expression was detected by Western blot. ResultA total of 1 044 putative targets for HBP were obtained from ETCM 2.0 and TCMIP v2.0. From the CTD， HPO， and SoFDA databases， 1 223 potential effect-related targets were identified. Cardiac transcriptome sequencing （RNA-seq） yielded 214 genes related to doxorubicin-induced myocardial injury and 58 genes associated with the effects of HBP， using criteria of P-value<0.05 and FC > 1.5/< 0.667. Analysis of the multidimensional molecular network revealed that the mechanisms of HBP on myocardial injury were mainly related to immune-inflammation imbalance， cellular metabolism， myocardial cell function and fibrosis， angiogenesis， contraction and platelet activation， DNA synthesis， metabolism and repair， as well as cell death and oxidative stress. HBP improved cardiovascular abnormalities such as reduced ejection fraction， myocardial fibrosis， myocarditis， hypertriglyceridemia， and arterial/venous thrombosis. Animal experiments demonstrated that HBP reduced the abnormal high expression of Nod-like receptor heat protein domain Protein 3 （NLRP3）， Caspase-1， apoptosis-associated speck-like protein （ASC）， and Gasdermin D （GSDMD） in myocardial tissue induced by doxorubicin （P<0.05）， and improved the elevated mRNA levels of fibrosis markers transforming growth factor-β₁ （TGF-β₁）， Smad3， and α-smooth muscle actin （α-SMA） （P<0.05）. ConclusionHBP can improve myocardial injury through multiple components， targets， and effects， with the inhibition of the NLRP3 inflammasome activation pathway being a key pharmacodynamic mechanism. This study is expected to provide new insights for the development of targeted therapeutic drugs.

Objective:To investigate the expression of miRNA-144 in the peripheral blood of patients with type 2 diabetes foot ulcer (DFU) and its correlation with the pathogenesis of the disease.Methods:A total of 106 patients with DFU admitted to the General Hospital of the Western Theater Command of the Chinese People′s Liberation Army from March 2020 to June 2022 were retrospectively selected as the observation group, and 106 patients with type 2 diabetes mellitus (T2DM) who did not have DFU admitted to our hospital during the same period were selected as the control group. According to the median expression level of miRNA-144 in peripheral blood of DFU patients as the segmentation point, 106 patients in the observation group were divided into low expression group and high expression group. We compared the clinical data of the observation group and the control group, and analyzed the relationship between different levels of miRNA-144 expression and clinical characteristics of DFU patients; A multivariate analysis was conducted on the factors related to the occurrence and development of the disease course in DFU patients, and a column chart model was constructed for model validation.Results:The course of diabetes, fasting blood glucose (FPG), erythrocyte sedimentation rate (ESR), glycosylated hemoglobin (HbA 1c), white blood cell count (WBC), C-reactive protein (CRP), corticotropin releasing hormone (CRH), interleukin-6 (IL-6), adrenaline (E), norepinephrine (NE), cortisol (Cor) and miRNA-144 expression levels in the observation group were significantly higher than those in the control group, while transcutaneous partial pressure of oxygen (TcPO 2), ankle brachial index (ABI), triglyceride (TG) and hemoglobin (Hb) were significantly lower than those in the control group, the difference was statistically significant (all P<0.05). There were statistically significant differences in foot ulcer healing rate, Wagner grading, and ulcer course between the high expression group of miRNA-144 and the low expression group of DFU patients after 8 weeks (all P<0.05). Multivariate regression analysis showed that the duration of diabetes>5 years, HbA 1c>8.5%, TcPO 2<60 mmHg, CRP>10 mg/L, Cor>190 μg/L, and miRNA-144 expression level>35 were independent risk factors for the occurrence of DFU in T2DM patients. The total score of 315 points after constructing the nomogram prediction model for the above factors, and the corresponding probability of occurrence and development of DFU was 72.56%. Conclusions:The expression level of miRNA-144 in the peripheral blood of DFU patients is significantly related to the occurrence and development of the disease course, and the course of diabetes and the changes of HbA 1c, TcPO 2, CRP, Cor levels are independent risk factors for the occurrence and development of DFU, which should be focused on clinically.

Objective:To evaluate the role of spinal Leucine-rich Repeat Kinase 2 (LRRK2) in neuropathic pain in rats.Methods:Fifty SPF healthy male Sprague-Dawley rats, aged 6-7 weeks, weighing 210-245 g, were divided into 5 groups ( n=10 each) using a random number table method: control group (C group), neuropathic pain group (NP group), low dose GNE-7915 group (low-dose GNE-7915 group), medium-dose GNE-7915 group (medium-dose GNE-7915 group), and high-dose GNE-7915 group (high-dose GNE-7915 group). Neuropathic pain was induced by the spared nerve injury in anesthetized rats. At 7 days after developing the model, LRRK2 inhibitor GNE-7915 12.5, 25.0 and 50.0 mg/kg were intraperitoneally injected in low-, medium- and high-dose GNE-7915 groups, respectively. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model, at 7 days after developing the model, and at 4 h after injecting the inhibitor. After measurement of the pain threshold, the rats were sacrificed and the spinal cord tissues were taken for determination of the positive expression of ionized calcium-binding adapter molecule 1(Iba-1) (by immunofluorescence staining), contents of interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and IL-18 (by enzyme-linked immunosorbent assay), positive expression of phosphorylated LRRK2 (p-LRRK2) (by immunofluorescence staining), and expression of LRRK2, IL-1β, MCP-1 and IL-18 (by immunoblotting). The ratio of p-LRRK2/LRRK2 was calculated. Results:Compared with C group, the MWT was significantly decreased, the TWL was shortened, the proportion of Iba-1 and p-LRRK2 positive cells in spinal cord tissues, contents of IL-1β, MCP-1 and IL-18, and p-LRRK2/LRRK2 ratio were increased, and the expression of IL-1β, MCP-1 and IL-18 proteins was up-regulated in NP group ( P<0.05). Compared with NP group, the MWT was significantly increased, the TWL was prolonged, the proportion of Iba-1 and p-LRRK2 positive cells in spinal cord tissues, contents of IL-1β, MCP-1 and IL-18, and p-LRRK2/LRRK2 ratio were decreased, and the expression of IL-1β, MCP-1 and IL-18 proteins was down-regulated in low-, medium- and high-dose GNE-7915 groups ( P<0.05). Conclusions:LRRK2 in the spinal cord may be involved in the pathophysiological mechanism of neuropathic pain by activating microglia and inducing inflammatory responses in rats.

Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.
Rats ; Animals ; Vascular Endothelial Growth Factor A/pharmacology* ; Brain Ischemia/metabolism* ; Ischemic Stroke ; Signal Transduction ; ARNTL Transcription Factors/pharmacology* ; Neovascularization, Physiologic/physiology*

Humans ; Nephritis, Hereditary/genetics* ; Astigmatism ; Mutation ; Collagen Type IV/genetics*

Objective:To understand the epidemiology, clinical characteristics and associated risk factors of severe adenovirus(ADV)pneumonia in children, providing the basis for targeted prevention and treatment.Methods:Clinical features of children with ADV pneumonia at Children′s Hospital of Soochow University from January 2011 to December 2020 were retrospectively analyzed.According to the severity of the disease, cases were divided into severe ADV pneumonia group and common ADV pneumonia group.The epidemiological and clinical characteristics of two groups were compared, and risk factors for the occurrence of severe ADV pneumonia were analyzed.Results:A total of 1 158 patients with ADV pneumonia were enrolled, including severe ADV pneumonia 104 cases(8.98%) and ordinary ADV pneumonia 1 054 cases(91.02%).The median age of severe ADV pneumonia group was 1.17 (0.83, 2.73) years, which was significantly younger than that of common ADV pneumonia group 3.16 (1.50, 4.50) years( P<0.05), and 77.89% (81/104) of them were younger than 3 years old.The occurrence of severe ADV pneumonia was predominant in winter and spring, accounting for 71.15% (74/104).Cough was present in 89.42% (93/104) and fever in 99.01% (103/104) of the severe ADV pneumonia group.Compared with the common ADV pneumonia group, the severe ADV pneumonia group had a significantly longer febrile time[10(6, 14)d vs. 5(4, 7)d, P<0.05], significantly higher incidence of shortness of breath, wheezing, convulsions/coma[100% vs. 2.09%, 45.19% vs. 13.57%, 10.57% vs. 1.99%, P<0.05], and significantly higher incidences of emphysema, pleural effusion, bronchial signs, pulmonary solids, and atelectasis [21.15% vs. 2.09%, 5.77% vs. 0.19%, 4.81% vs. 0, 3.85% vs. 0.09%, P<0.05].Multivariable Logistic regression showed that age younger than 1.71 years old, wheezing, and the presence of underlying diseases (moderate to severe anaemia, congenital heart disease, neurological disease) were risk factors for the development of severe ADV pneumonia ( P<0.05).Receiver operating characteristic curve analysis showed that the sensitivity and specificity of age<1.71 years old(20 months old) for predicting the occurrence of severe ADV pneumonia were 65.4% and 71.5%, respectively. Conclusion:The age of most severe ADV pneumonia is less 3 years in Suzhou.It usually occurres in winter and spring, with fever, cough, shortness of breath, and wheezing as the main symptoms.Pulmonary manifestations such as pleural effusion, emphysema, pulmonary consolidation, and atelectasis may occur.The underlying disease, wheezing, and age of onset less than 1.71 years (20 months) old are independent risk factors for severe ADV pneumonia.