Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

OBJECTIVE To systematically evaluate the regulatory effect of liraglutide on hypoglycemia in patients with type 1 diabetes mellitus （T1DM） and provide evidence for the prevention and control of hypoglycemia in the clinical treatment of T1DM. METHODS Electronic databases including The Cochrane Library， PubMed， Embase， Web of Science， China Biology Medicine Disc （CBM）， CNKI， Wanfang database， and VIP database were searched from the inception of the databases to June 30， 2023. The clinical randomized controlled trials （RCTs） of liraglutide on hypoglycemia in T1DM patients were screened according to inclusion and exclusion criteria. Data extraction， grouping， and subgroup meta-analysis were conducted for the included studies. RESULTS A total of 11 RCTs involving 1 685 patients were ultimately included. Meta-analysis results showed that treatment with 1.2 mg liraglutide could reduce the frequency of hypoglycemia in patients with T1DM [OR＝0.81， 95%CI （0.74， 0.88）， P＜0.01]， while treatment with 1.8 mg liraglutide could increase the frequency of hypoglycemia [OR＝1.33， 95%CI （1.23， 1.44）， P＜0.01]. The effect of liraglutide on hypoglycemia in patients with T1DM was not correlated with the duration of hypoglycemia [MD＝ －0.29， 95%CI （－1.21， 0.63）， P＝0.53]， and did not increase the incidence of severe hypoglycemia in these patients [OR＝0.87， 95%CI （0.57， 1.33）， P＝0.53]. Liraglutide could reduce the levels of glycated hemoglobin [MD＝－1.39， 95%CI （－2.65， －0.13）， P＝0.03]， weight [MD＝－4.28， 95%CI （－5.01， －3.55）， P＜0.01]， and body mass index [MD＝－1.20， 95%CI （－1.80， －0.60）， P＜0.01] in them. CONCLUSIONS Liraglutide has a bidirectional regulatory effect on hypoglycemia in patients with T1DM， which is correlated with the dose of liraglutide. An appropriate dose of liraglutide （1.2 mg） can inhibit hypoglycemia in these patients， while an increased dose of liraglutide （1.8 mg） can promote hypoglycemia in them.

Objective:To evaluate the clinical effectiveness and safety of combined face and neck injections of botulinum toxin type A to improve face and neck aging.Methods:From January 2020 to January 2023, 30 female patients with age of 29-66 years, average (42.2±8.8) years, underwent face and neck combined injection of A-type botulinum toxin in the Department of Dermatology, Henan Provincial People′s Hospital. The injection sites included the forehead, between the eyebrows, around the eyes, the dorsum of the nose, and the mandibular margin, etc. The efficacy was assessed by the wrinkle severity scale (FWS) and the AB value of the distance from the lowest point of the mandibular margin on the midline of the hemiface to the level of the medial canthus at 4 and 24 weeks after the injection, as well as the subjective degree of improvement by the Global Aesthetic Improvement of the Face Scale (GAIS) and the Self-perception of Age (SPA), and the satisfaction of the patients and post-injection adverse reactions.Results:At 4 weeks after the injection, the total effective rate of improvement of wrinkles in all parts of the upper face was 100% (30/30), and there was a statistically significant difference in the improvement of AB ( t=28.35, P<0.05). At 24 weeks after the injection, the total effective rate of improvement of wrinkles in all parts of the upper face ranged from 16.7% (5/30) to 36.7% (11/30), and the improvement of AB still showed a statistically significant difference ( t=3.98, P<0.05). 100% (30/30) and 66.7% (20/30) of patients assessed their facial status as improved on GAIS at 4 and 24 weeks after the injection, respectively, and 100% (30/30) and 63.3% (19/30) of patients perceived themselves as younger. Patient satisfaction was 100% (30/30). After injection, there were 5 cases of slight ecchymosis at the injection site and 1 case of weakness in eyebrow elevation in the 30 patients, which disappeared on their own within 1 to 2 weeks. Conclusions:The therapeutic effect of face and neck combined injection of botulinum toxin type A on facial rejuvenation is obvious, with high patient′s satisfaction and no serious adverse reactions.

Performance appraisal of public hospitals have given a guidance for the development of public hospitals at all levels.A Class A tertiary hospital reviewed the problems in the development of the hospital at the present stage and focused on the following four aspects:①insufficient fine management;②No clear orientation of discipline development;③The bottleneck of the improvement of medical operation efficiency;④New challenges in the reform of payment mode.The tertiary hospital launched a fine management practice in May 2022,in order to solve the problems by taking the Department of Surgery as a pilot area,laying the foundation for fine management through information system construction,improving the efficiency of medical operation through management process optimization,improving the overall competitiveness of disciplines through the construction of sub-specialty and Discipline Alliance and adjusting the performance appraisal index system to play the role of performance incentives.The measures effectively improve the overall capacity and efficiency of hospital medical services and help the hospital to achieve high-quality development.

Objective:To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China.Methods:A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors.Results:The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A ( χ2=7.91 and 8.06, both P=0.005) and vitamin D ( χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively ( OR=0.68 and 0.22, 95% CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB ( χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively ( χ2=93.22 and 202.54, both P<0.001). Conclusions:Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.

Objective To analyze the coding quality of multiple primary malignant tumors in a tertiary hospital,identify existing problems,and improve the accuracy of coding for multiple primary malignant tumors.Methods We collected 393 medi-cal records from a tertiary hospital from June 1,2021,to June 30,2023,with ICD-10 code C97 for the discharge diagnosis.By carefully reading the medical records,we analyzed the reasons for coding errors in multiple primary malignant tumors with code C97.Results Among the 393 medical records,there were 34 cases with coding errors in C97,including 11 cases where meta-static malignant tumors were erroneously coded as multiple primary malignant tumors,9 cases where malignant tumors of the same organ system with non-adjacent sites and the same histological type were erroneously coded as multiple primary malignant tumors,7 cases where distant metastasis or local invasion was erroneously coded as multiple primary malignant tumors,4 cases where be-nign tumors were mistakenly coded as malignant tumors,and 3 cases where suspected malignant tumors were coded as confirmed cases.Conclusion To improve the quality and efficiency of C97 coding,coders need to have a clear understanding of the defini-tion of multiple primary malignant tumors,read the medical records carefully and completely,determine the location and histolog-ical type of the tumors accurately,and strengthen communication with clinical physicians.

Coding malignant tumors in multiple sites within the digestive system involves some coding rules.When more than two malignant tumors present various pathologic types,they should be included in the code of C97,which indicates multiple primary malignancies,and should be categorized into a specific code under the category of C97 upon corresponding treatment pur-poses.For those malignant tumors in the digestive system presenting with the same pathological results but unidentified primary sites,which are diagnosed as more than two types of tumors and recorded on the first page of a medical record,they are coded ac-cording to their specific locations.The coding principles are as followed:① If a malignant tumor spans two or more adjacent sites with an unidentified primary origin,it should be classified as a cross-site malignant tumor and coded based on the tumor's ana-tomical location.② If more than two malignant tumors are located in the separate parts of the same location,they should be co-ded with".9"as a subheading of the three-digit category specific to the right location.③If more than two malignant tumors are not adjacent to each other in the digestive system,they should be classified to the code of C26.9.In the process of coding,cod-ers should review case data thoroughly,enhance the accumulation of clinical knowledge,and strengthen communications with doc-tors,thereby enhancing coding precision.

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4⁺/CD8a⁺ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Objective To address the issue of missing entity relationship information in the knowledge graph of TCM ancient books;To propose a knowledge reasoning method based on deep reinforcement learning;To improve the completeness of the knowledge graph.Methods Based on the benchmark dataset in the field of knowledge graph and the dataset of TCM ancient books,a deep reinforcement learning inference method was adopted.Combined with knowledge one-step completion and multi hop path search,Python language was used in conjunction with the Neo4j graph database to achieve path to path inference.Results In the knowledge reasoning task dataset,compared with the baseline model,this reasoning method improved the MAP index by about 53.79%.When applied to the knowledge graph of TCM ancient books,its evaluation index reached the highest of 0.776.Conclusion The knowledge reasoning method based on deep reinforcement learning has significant advantages in improving the completeness of the knowledge graph of TCM ancient books,and this method can effectively fill the information gap in the graph of TCM ancient books.

The pathogenesis of bipolar disorder(BD)is unknown,and objective biomarkers with clinical guidance are lacking.Extracellular vesicles(EV)are lipid bilayer-enclosed vesicles that carry cargo from originating cells,influencing the processes of recipient cells.They are capable of crossing the blood-brain barrier and reflecting the ongoing processes in the central nervous system.Compelling data indicates that EV could mediate BD pathophysiological processes such as neurocognitive impairment,neuroinflammatory diffusion,and metabolic dysfunction.Therefore,EV has the potential to become a reliable biomarker and therapy for BD,providing new ideas for revealing the pathogenesis and clinical diagnosis and treatment of BD.