Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Using big data and artificial intelligence to establish a multi-point monitoring, early warning, and disposal system to achieve early warning and intervention of infectious disease outbreaks is an important means of controlling the spread of the epidemic. Taking Xiaoshan district as an example, this study analyzes the monitoring contents, warning methods, and application effectiveness of the infectious disease monitoring, early warning and disposal system. Based on Xiaoshan′s health big data resources, the system starts with syndrome, disease diagnosis and etiology. Through advanced technologies such as artificial intelligence and block chain, it realizes early identification of infectious disease outbreaks, data fusion, multi-cross collaboration, and closed-loop management. It has improved the sensitivity of clustered outbreaks monitoring and the effectiveness of epidemic disposal and provided a reference for grassroots disease prevention and control departments to establish an infectious disease monitoring and early warning system.

Using big data and artificial intelligence to establish a multi-point monitoring, early warning, and disposal system to achieve early warning and intervention of infectious disease outbreaks is an important means of controlling the spread of the epidemic. Taking Xiaoshan district as an example, this study analyzes the monitoring contents, warning methods, and application effectiveness of the infectious disease monitoring, early warning and disposal system. Based on Xiaoshan′s health big data resources, the system starts with syndrome, disease diagnosis and etiology. Through advanced technologies such as artificial intelligence and block chain, it realizes early identification of infectious disease outbreaks, data fusion, multi-cross collaboration, and closed-loop management. It has improved the sensitivity of clustered outbreaks monitoring and the effectiveness of epidemic disposal and provided a reference for grassroots disease prevention and control departments to establish an infectious disease monitoring and early warning system.

Objective:To investigate the gene transcription level changes in the amygdala of social isolation rearing models of schizophrenia to determine the pathogenic genes and their related pathways of schizophrenia.Methods:A total of 29 3-week-old SPF C57BL/6J male mice were randomly divided into control group ( n=16) and model group ( n=13); 4 mice were raised in each transparent mouse cage in the control group, and 1 mouse was raised in each transparent mouse cage in the model group; mice in each cage could see their surrounding mice but could not touch each other. Mice in both groups were fed for 4 weeks and then subjected to open field experiment, pre-pulse inhibition experiment and new object recognition experiment within one week. After the experiment, mice were sacrificed by spinal dislocation, and the amygdala was taken for transcriptome sequencing. The topGO software was used for gene ontology (GO) functional enrichment analysis of differentially expressed genes (DEGs), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using KEGG database. Results:(1) Animal experiment: compared with the control group, the model group had significantly increased movement distance in the open field experiment ([1 239.20±106.35] m vs. [1 845.53±143.65] m, t=3.464, P=0.002), significantly decreased activity time in the central region 5 min before experiment ([13.15±1.41] s vs. [8.47±1.19]) s, t=2.464, P=0.020). Compared with the control group, the model group had significantly lower percentage of deficient prepulse inhibition (PPI) of 78 dB ([22.28±1.53] % vs. [14.59±2.75] %, t=2.629, P=0.013), and deficient PPI of 88 dB ([32.83±3.39] % vs. [18.44±3.07] %, t=3.081, P=0.005). Compared with the control group, the model group had significantly decreased ratio of time exploring new objects/time exploring former objects ([80.5±2.2]% vs. [71.0±3.6]%, t=2.356, P=0.026). (2) Bioinformatics analysis: a total of 96 DEGs were found, of which 42 were with up-regulated expressions ( Th, Crlf1, etc.), and 54 were with down-regulated expressions ( Prkcd, etc.). Th and Crlf1 were positively correlated ( r=0.940, P=0.018). GO enrichment results suggested that DEGs were enriched in projection function of plasma membrane boundary cells, neuronal differentiation, and cell apoptosis. KEGG enrichment results suggested that DEGs were enriched in WNT signaling pathway, apoptosis pathway and tyrosine metabolism pathway. Protein network interaction analysis suggested that Wnt6, Tcf712, Pitx2, Tcf7 and Cd4 were key proteins. Conclusion:DEGs such as Th, Prkcd, Lrrc74b, Fadd, Wnt6, Ror2, Notum, and Tcf7l2, and their related signaling pathways may be related to schizophrenia in the amygdala of social isolation rearing mice.

Objective:To analyze the characteristics of adverse events of active medical devices in Shandong province, as well as the impact of device use duration on the risk rate of adverse events, for reference in improving the monitoring system of active medical device adverse events in China and the level of hospital medical quality management.Methods:The data came from the adverse event reporting data of active medical devices collected by Shandong Adverse Drug Reaction Monitoring Center from January 2019 to October 2021. The R software was used to analyze the distribution, cause and severity of adverse events, and a linear regression model of adverse event risk rate(Y) and adverse event time point(X) was established.Results:A total of 35 254 adverse events of active devices were included, of which 3 059 were serious injuries. The province/municipality with the largest number of reported adverse events was Shanghai(8 006 cases), and the least was Hainan province(4 cases); The majority of adverse events were reported by hospitals, with 34 056(96.60%). The medical devices reporting a higher number of adverse events were ventilators(688 cases), monitors(4 623 cases), infusion pumps(1 079 cases), syringe infusion pumps(1 995 cases), medical electron accelerators(529 cases)and infant incubators(513 cases). In the linear regression model, the risk rate of adverse events increased with the useduration of the device when 0.00%≤ X<14.14%; the risk rate of adverse events decreased with the increase of service time when 14.14%≤ X<100.00%. Conclusions:The number of adverse events reported in each province is different, and hospitals are the main reporting units.The causes of adverse events of different medical devices indicate different correlation strengths with the product itself. The use duration of medical devices poses a great impact on the risk rate of adverse events.

Objective:To investigate the safety and efficacy of Tubridge flow diverter for the treatment of recurrent internal carotid blood blister-like aneurysms after stent-assisted embolization.Methods:From June 2018 to April 2021, patients with recurrent internal carotid blood blister-like aneurysms treated with Tubridge flow diverter in the Department of Neurosurgery, Changhai Hospital, Naval Medical University were enrolled retrospectively. The perioperative safety, immediate postoperative and follow-up results were analyzed.Results:A total of 6 patients with recurrent internal carotid blood blister-like aneurysm after stent-assisted embolization were enrolled. The time interval from the first stent-assisted embolization to Tubridge placement was 14 to 90 d. Tubridge implantation alone was used in 4 patients, and Tubridge was implanted in the other 2 patients after the coils were packed. There were no complications during the perioperative period, and no rebleeding was observed after clinical follow-up for 5 to 36 months. Five patients were followed up by angiography for 1-3 months, and the aneurysms disappeared completely.Conclusion:Tubridge flow diverter for the treatment of recurrent internal carotid blood blister-like aneurysms is safe and effective.

Background and Objectives: Induced pluripotent stem cells (iPSCs) are usually generated by reprogramming differentiated cells through the introduction of specific transcription factors, but this is a difficult and inefficient process.Valproic acid (VPA) is a histone deacetylase inhibitor that significantly improves the efficiency of iPSC generation.But its role and mechanism are still unclear. Methods: and Results: We transduced Bactrian camel fetal fibroblasts (BCFFs) with retroviruses carrying defined factors (OCT4, SOX2, KLF4, c-MYC and EGFP; OSKMG) in the presence of VPA. Cells were collected (Day 7) and analyzed using RNA-seq technology. Afterwards, different groups of cells and transcriptomics results were detected by PCR and qRT-PCR technology. The results showed that VPA promoted the expression of the endogenous gene c-Myc and inhibited cell proliferation; at the same time, it promoted the expression of VEGF and other genes related to angiogenesis. Conclusions When VPA is added to the culture medium, only the cells that have begun to reprogram can break the G2/M repression through the expression of the endogenous gene c-Myc, and use the nutrients and space in the culture dish to proliferate normally, which can achieve the purpose of directly improving the efficiency of reprogramming.Another new discovery for Bactrian camels, VPA significantly increased the expression of VEGFC and other genes, promoting the transformation of fibroblasts to endothelial cells (different from the mesenchymal-to-epithelial transition process of other species) to accelerate the early induction of Bactrian camels iPSc process. Overall, this study proved the new mechanism of VPA in enhancing the induction of pluripotency from the transcriptome level.

Background and Objectives: Induced pluripotent stem cells (iPSCs) are usually generated by reprogramming differentiated cells through the introduction of specific transcription factors, but this is a difficult and inefficient process.Valproic acid (VPA) is a histone deacetylase inhibitor that significantly improves the efficiency of iPSC generation.But its role and mechanism are still unclear. Methods: and Results: We transduced Bactrian camel fetal fibroblasts (BCFFs) with retroviruses carrying defined factors (OCT4, SOX2, KLF4, c-MYC and EGFP; OSKMG) in the presence of VPA. Cells were collected (Day 7) and analyzed using RNA-seq technology. Afterwards, different groups of cells and transcriptomics results were detected by PCR and qRT-PCR technology. The results showed that VPA promoted the expression of the endogenous gene c-Myc and inhibited cell proliferation; at the same time, it promoted the expression of VEGF and other genes related to angiogenesis. Conclusions When VPA is added to the culture medium, only the cells that have begun to reprogram can break the G2/M repression through the expression of the endogenous gene c-Myc, and use the nutrients and space in the culture dish to proliferate normally, which can achieve the purpose of directly improving the efficiency of reprogramming.Another new discovery for Bactrian camels, VPA significantly increased the expression of VEGFC and other genes, promoting the transformation of fibroblasts to endothelial cells (different from the mesenchymal-to-epithelial transition process of other species) to accelerate the early induction of Bactrian camels iPSc process. Overall, this study proved the new mechanism of VPA in enhancing the induction of pluripotency from the transcriptome level.

In addition to causing high disability and high fatality rates, ruptured intracranial aneurysms can also cause cognitive impairment. Although preventive surgical treatment can avoid intracranial aneurysm rupture and bleeding, patients may still have a certain degree of cognitive impairment, even in patients with good clinical recovery after surgery. There is no systematic review on the effect of different surgical methods on cognitive function, and the best surgical method is still inconclusive. This article reviews the cognitive impairment in patients with intracranial aneurysm, hoping to provide a basis for clinical treatment decisions.

Objective To investigate the curative effect of sodium hyaluronate intraperitoneal injection combined with oral Yanghe decoction in the treatment of knee osteoarthritis .Methods 80 patients with knee osteoar-thritis were randomly divided into two groups ,40 cases in each group .The control group was given intra -articular injection of sodium hyaluronate ,and the study group was treated with Yanghe decoction in addition .The TCM symptom score , knee joint index , overall treatment effect and quality of life were compared between the two groups .Results The total score of TCM symptoms after treatment in the study group was (7.08 ±1.18)points,which was significantly lower than (10.42 ±2.01)points in the control group(t=9.063,P<0.01).The VAS score and WOMAC score after treatment in the study group were (1.48 ±0.59)points,(19.10 ±3.08)points,respectively,which were significantly lower than (3.70 ±1.12)points and (23.40 ±3.56)points in the control group (t=11.091,5.777,all P<0.01). The HSS score after treatment in the study group was (83.04 ±10.49) points,which was significantly higher than (71.81 ±9.67)points in the control group(t =4.978,P<0.01).The physiological function,physical function, physical pain,mental health and energy scores after 6 months treatment in the study group were significantly higher than those in the control group (t=5.190,8.535,4.569,3.266,6.694,all P<0.01).The effective rate and total effective rate of the study group were 72.5％and 95.0％,respectively,which were significantly higher than those of the control group(50.0％,77.5％),the differences were statistically significant (χ2 =4.266,5.165,all P<0.05). Conclusion Sodium hyaluronate injection combined with oral Yanghe decoction is effective in the treatment of knee osteoarthritis.