The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain, yet the precise neural mechanisms underlying this association remain elusive. In our study, we explored the contribution of cholinergic neurons within the medial habenula (MHb) to hyperalgesia induced by sleep deprivation in rats. Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results. Interestingly, we did not find a direct response of MHb cholinergic neurons to pain stimulation. Further investigation identified the interpeduncular nucleus (IPN) and the paraventricular nucleus of the thalamus (PVT) as key players in the pro-nociceptive effect of sleep deprivation. Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia. These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation, highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia.
Animals ; Habenula/physiology* ; Sleep Deprivation/physiopathology* ; Cholinergic Neurons/physiology* ; Male ; Hyperalgesia/physiopathology* ; Rats, Sprague-Dawley ; Rats ; Interpeduncular Nucleus/physiology* ; Pain Threshold/physiology* ; Midline Thalamic Nuclei/physiology* ; Neural Pathways/physiopathology*

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies

The problems of the syndrome differentiation of migraine in acupuncture treatment were collected, e.g. inconsistency of syndrome differentiation, unclear staging of syndrome differentiation, lack of standardization in comparison between syndrome differentiation and non-differentiation, insufficient research on the factors of syndrome differentiation. In view of the exiting problems, focusing on two aspects of migraine, namely syndrome differentiation and acupuncture effect, the clinical treatment and research are conducted in migraine treated with acupuncture based on syndrome differentiation. It is believed that the comprehensive observation of the relationship between syndrome differentiation and acupuncture effect, as well as the analysis of the relevant factors of syndrome differentiation of migraine should be the focus in future research.
Acupuncture Therapy ; Humans ; Migraine Disorders ; therapy ; Treatment Outcome

OBJECTIVE: To explore the genetic basis of cerebral palsy (CP). METHODS: A pair of twins with cerebral palsy and different phenotypes were subjected to whole genome sequencing, and other 8 children with CP were subjected to whole exome sequencing. Genetic variations were screened by a self-designed filtration process in order to explore the CP-related biological pathways and genes. RESULTS: Three biological pathways related to CP were identified, which included axon guiding, transmission across chemical synapses and protein-protein interactions at synapses, and 25 susceptibility genes for CP were identified. CONCLUSION The molecular mechanism of CP has been explored, which may provide clues for development of new treatment for CP.
Cerebral Palsy ; genetics ; Child ; Genetic Testing ; Humans ; Phenotype ; Whole Exome Sequencing ; Whole Genome Sequencing

[Objective]To investigate the effects of peripheral form-deprivation and central form-deprivation on em-metropization of infant rhesus monkeys.[Methods]Nineteen healthy infant rhesus monkeys,about 3 weeks of age,were divided into three groups of A(n=6),B(n=6)and C(n=7)by random.The monkeys from group A wore peripheral form-deprivation spectacle lenses over both of their eyes.The monkeys from group B wore central form-deprivation lenses over both of their eyes.The monkeys from group C were 0.00 Dlenses over both of their eyes as control.The monkeys'refractive error,corneal topography,vitreous chamber depth were measured at the start of lens wear and at 2 weeks,1.5 months, 2 months,3 months post-treatment. By these means,we can observe the changes of eye growth and refractive status dynamically.[Results]In group A,B and C,no statistically significant difference was observed between the right and left eyes in vitreous chamber depth and refractive errors pre-and post-treatment(P>0.05).During the course of study,the vitreous chamber depthelongated gradually and refractive status became less hyperopic in all animals.After 3 months'lens wear,the axial eyeball elongation amplitude(mm)of group A(peripheral form-deprivation group,1.25±0.36)monkeys was more obvious than that of group C(control group,0.55±0.19,P=0.001),but there was no statistically significant difference between group B(0.59±0.14)and C(P=0.807).The decrease of hyperopic degrees(D)of group A monkeys (-4.44±1.33)was more obvious than that of group C(-1.83±0.58,P=0.000).The eyes of group A monkeys appeared a remarkable myopic shift after treatment. No statistically significant difference was found between group B(-2.25±0.31) and C in hyperopic degrees reduction(P=0.383). Before and after lens wear,no statistically significant difference was found within or between groups in corneal Sim K values(P>0.05).[Conclusion]During the emmetropization process of infant rhesus monkeys,if the visual signals from peripheral retina are in conflict with those from central retina,the former will play a dominant role.

AIM:To investigate the differences of clinical signs and pathological structure of unilateral nasal pterygium and unilateral double pterygium.METHODS:Retrospective study.Totally 11 unilateral nasal pterygium and 11 unilateral double pterygium were collected to observe the size of the tissue area, the classification of blood vessels, the transparency and the break-up time of tear film.The 11 surgically excised double pterygia (11 eyes) and 6 samples of normal conjunctiva were collected for the study.With 40g/L paraformaldehyde fixation, paraffin sections were stained with Haematoxylin-Eosin, to observe the differences with nasal and temporal pathology under light microscope.RESULTS:In unilateral double pterygium, the tear break-up time was significantly shorter than that of unilateral nasal pterygium (t=3.410, P=0.003).In unilateral nasal pterygium, there was a significant negative correlation between tear film break-up time and tissue size(r=-0.927, P<0.01) and transparency(r=-0.764,P<0.01).In unilateral double pterygium, the tear break-up time was significantly negatively correlated with the growth time (r=-0.661, P<0.05), tissue size (r=-0.775, P<0.01) and transparency (r=-0.671,P<0.05).In unilateral double pterygium, compared with the temporal side, the quantity of the layers of corneal epithelial cells (t=-7.351, P<0.05), vessels (t=-7.400, P<0.05) and inflammatory cells (t=-7.481, P<0.05) increased.CONCLUSION:Compared with unilateral nasal pterygium, the tear film break-up time of unilateral double pterygium was poor.In unilateral double pterygium, with high activity, the degree of proliferation of squamous epithelium, hyperplasia and inflammatory reaction are significantly higher than those of the temporal side.

Objective To investigate the risk factors and prognosis of peritoneal dialysis (PD)related bacterial peritonitis.Methods The clinical data of patients with PD related bacterial peritonitis from January 2006 to September 2016 in our hospital were retrospectively analyzed and followed up until December 2016.Patients were divided into two groups according to the frequency of peritonitis,single episode group and multiple episodes group (no less than two episodes of peritonitis).According to efficacy of therapy,the episodes of peritonitis were divided into two groups,cured group (no relapse,recurrence or repeat episodes) and failure group (relapse,recurrent or repeat infection after the therapy of initial episode).Logistic regression and Cox regression were used to analyze the risk factors for outcomes.Results Five hundred and fifty-nine patients had PD related bacterial peritonitis,including 339 patients in the single episode group and 220 patients in the multiple episodes group.Logistic analysis showed low serum albumin level (OR=787,P ＜ 0.001) and malnutrition (OR=0.422,P ＜ 0.001) at baseline were independent risk factors for multiple episodes (P ＜ 0.001).The technical survival was better in the single episode group than that in the multiple episodes group (75.2％ vs 36.2％,P=0.001) while the difference of survival rate was not significant between the two groups (48.2％ vs 24.1％,P=0.592).Five hundred and thirteen episodes of peritonitis were analyzed,including 147 episodes in failure group (88 relapse episodes,16 recurrent episodes and 43 repeat episodes) and 366 episodes in cured group.There were 78 patients in failure group and 253 patients in cured group.Logistic analysis showed prolonged response time (OR=1.200,P ＜ 0.001),Gram-positive bacteria infection (OR=1.736,P=0.022),higher hs-CRP level (OR=1.004,P=0.013),lower serum albumin level (OR=0.936,P=0.008) were independent risk factors for failure of therapy.Multivariate Cox regression showed prolonged response time (HR=1.120,P=0.032),Gram-positive bacteria infection (HR=2.462,P=0.002),higher hs-CRP level (HR=1.007,P=0.009) were independent risk factors for failure of therapy and higher serum albumin level (HR=0.942,P=0.048) was an independent protection factor.Conclusions Low serum albumin level and malnutrition at baseline are independent risk factors for patients with multiple peritonitis episodes.Prolonged response time,Gram-positive bacteria infection,the high hs-CRP level are independent risk factors for relapse or recurrent or repeat episodes while high serum albumin level was an independent protection factor.

Objective To identify the epidemic characteristics and risk factors of an emerging infectious disease-severe fever with thrombocytopenia syndrome (SFTS) in Hubei province.Methods Active surveillance program on SFTS was set up in monitoring sites-hospitals,at the township level or above,in Suizhou,Huanggang and Wuhan from January to December,2010.Specific surveillance program on SFTS was launched across the province in hospitals above the county level.Cases that matched the definition of surveillance case were identified and reported to Centers for Disease Control and Prevention (CDCs).Cases were interviewed and their blood samples collected and detected using PCR and virus isolation.We also conducted serum antibody surveys among healthy population and livestock and surveillance on vector ticks in those high-epidemic areas.Results 188 cases that matched the definition of surveillance case and 21 deaths were reported in 11 cities,32 countries and 100 towns in 2010,with an incidence rate of 0.33/106.The fatality rate was 11.2％.Data showed that the patients were from hilly areas at the altitude elevated between 28-940 meters.The epidemic period was between April and December with the peak from May to September.The youngest case was an 11-year old,while the eldest was 81 with median age as 56-year old.95.3 ％ of the patients were farmers.All Patients did not have the history of traveling,two weeks before the onset of SFTS.93.6％ of the patients engaged in different kind of work which was associated with agriculture.52.8％ of the patients had been exposed to ticks.22.0％ of the patients had been bitten by ticks.Skin injury was found in 64.2％ of the patients.Samples from 129 cases (68.6％) were collected and detected,with 67.4％ of them (87 cases) showed positive by Real time-PCR for SFTS virus.An elevation in antibody titer by a factor of four or evidence of sero-conversion was observed in 11 patients; SFTS virus was isolated from 2 patients.The total antibody positive rates were 3.8％,55.0％ (6/11 ),36.7％ (2/3) and 80.0％ (4/5) respectively in healthy population,dogs,sheep and cows.Ticks from grass,cattle and sheep were detected positive by Real time-PCR.Conclusion Most cases of SFTS in Hubei were infected by SFTS virus,and cases of livestock were infected by SFTS virus.Ticks might serve as an important vector.Skin injury,exposure to tick bites seemed to be the risk factors.