Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system. While the spleen may influence neuropathic pain, its role has been poorly understood. This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis (BNST) - paraventricular nucleus of the hypothalamus (PVN) neural circuit in a chronic constriction injury (CCI) mouse model. Splenectomy, splenic denervation, or splenic sympathectomy significantly increased the mechanical withdrawal threshold (MWT) and reduced macrophage infiltration in the dorsal root ganglia (DRG) of CCI mice. Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain. Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT; these effects were reversed by splenectomy, splenic denervation, or sympathectomy. These findings underscore the critical role of the spleen, regulated by the BNST-PVN circuit, in neuropathic pain.
Animals ; Neuralgia/pathology* ; Septal Nuclei/physiopathology* ; Male ; Spleen/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Mice, Inbred C57BL ; Splenectomy ; Mice ; Neural Pathways/physiopathology* ; Disease Models, Animal ; Ganglia, Spinal/physiopathology* ; Sympathectomy ; Macrophages

OBJECTIVE: To explore the association between blood glucose trajectories within 7 days of intensive care unit (ICU) admission and mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS). METHODS: Based on the MIMIC-IV database, sepsis-associated ARDS patients with daily blood glucose monitoring data within 7 days of ICU admission were selected. Blood glucose trajectories were analyzed using group-based trajectory modeling (GBTM), and the optimal number of groups was determined based on the minimum Akaike information criterion (AIC), Bayesian information criterion (BIC), average posterior probability (AvePP), odds of correct classification (OCC), and proportion of group membership (Prop). Baseline characteristics including demographics, comorbidities, severity scores, vital signs, laboratory indicators within the first 24 hours of ICU admission, and treatments were collected. Kaplan-Meier survival curves were used to compare 28-day and 1-year survival across trajectory groups. Multivariate Logistic regression was performed to evaluate the associations between glucose trajectory groups and in-hospital mortality, ICU mortality. The incidence of hypoglycemia within 7 days in the ICU was analyzed among different groups. RESULTS: A total of 3 869 patients with sepsis-associated ARDS were included, with a median age of 63.52 (52.13, 73.54) years; 59.6% (2 304/3 869) were male. Based on glucose levels within 7 days, patients were categorized into three groups: persistent hyperglycemia group (glucose maintained at 10.6-13.1 mmol/L, n = 894), moderate glucose group (7.8-8.9 mmol/L, n = 1 452), and low-normal glucose group (6.1-7.0 mmol/L, n = 1 523). There were statistically significant differences in 28-day mortality and 1-year mortality among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [28-day mortality: 11.42% (174/1 523), 19.83% (288/1 452), 25.50% (228/894), χ ² = 82.545, P < 0.001; 1-year mortality: 23.31% (355/1 523), 33.75% (490/1 452), 39.49% (353/894), χ ² = 77.376, P < 0.001]. Kaplan-Meier analysis showed that higher glucose trajectories were associated with significantly lower 28-day and 1-year cumulative survival rates (Log-rank test: χ ² were 83.221 and 85.022, both P < 0.001). There were statistically significant differences in in-hospital mortality and ICU mortality among the low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [in-hospital mortality: 9.65% (147/1 523), 19.70% (286/1 452), 24.50% (219/894), χ ² = 102.020, P < 0.001; ICU mortality: 7.22% (110/1 523), 16.05% (233/1 452), 20.13% (180/894), χ ² = 93.050, P < 0.001]. Logistic regression confirmed that, using the persistent hyperglycemia group as the reference, the low-normal glucose group had significantly lower risks of in-hospital mortality and ICU mortality after multiple factor adjustment. Although the moderate glucose group showed a trend toward lower mortality, the differences were not statistically significant. Using the moderate glucose group as a reference, the low-normal glucose group had 43.1% lower in-hospital mortality [odds ratio (OR) = 0.569, 95% confidence interval (95%CI) was 0.445-0.726, P < 0.001] and 42.0% lower ICU mortality (OR = 0.580, 95%CI was 0.439-0.762, P < 0.001). There was no statistically significant difference in the incidence of hypoglycemia within 7 days of ICU admission among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [2.82% (43/1 523), 2.69% (39/1 452), 3.02% (27/894), χ ² = 0.226, P = 0.893]. CONCLUSIONS Blood glucose trajectories during ICU stay are closely associated with prognosis in patients with sepsis-associated ARDS. Persistent hyperglycemia (10.6-13.1 mmol/L) is linked to significantly higher short- and long-term mortality.
Humans ; Respiratory Distress Syndrome/etiology* ; Sepsis/blood* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Blood Glucose/metabolism* ; Hospital Mortality ; Aged

Objective:To evaluate the role of lactate dehydrogenase in diabetic neuropathic pain (DNP) and the relationship with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in mice.Methods:SPF-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 18-22 g, were used to establish diabetes mellitus model by intraperitoneal injection of streptozotocin (STZ) 120 mg/kg. Twenty-four mice with diabetes mellitus were divided into 2 groups ( n=12 each) using a random number table method: DNP group and DNP + oxamate group (OXA group). Another 12 SPF-grade healthy male C57BL/6J mice were selected as control group (C group). In OXA group, oxamate 750 mg/kg was intraperitoneally injected once a day for 28 consecutive days. The equal volume of normal saline was given instead in C group and DNP group. The mechanical paw withdrawal threshold (MWT), blood glucose and body weight were measured at 3 days before STZ injection and at 1, 2, 3 and 4 weeks after STZ injection (T 0-4). After the last behavioural test was completed, blood samples were collected from the posterior orbits of anesthetized mice for determination of serum lactate concentrations. The animals were then sacrificed and the tissues from the prefrontal cortex of the brain were taken for determination of lactate content, mitochondrial membrane potential (by the JC-1), content of reactive oxygen species (ROS) (using dihydroethidium probes), and level of histone lactylation and expression of PGC-1α (by Western blot). Results:Compared with C group, the MWT was significantly decreased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were increased, the mitochondrial membrane potential was decreased, and the expression of PGC-1α was down-regulated in DNP and OXA groups ( P<0.05). Compared with DNP group, no significant change was found in blood glucose and body weight ( P>0.05), the MWT was significantly increased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were decreased, the mitochondrial membrane potential was increased, and the expression of PGC-1α was up-regulated in OXA group ( P<0.05). Conclusions:Lactate dehydrogenase promotes the development of DNP, and the mechanism is related to promotion of increase in histone lactfication and down-regulation of PGC-1α expression in the prefrontal cortex of mice.

Objective:To explore the potential mechanisms of the relationship between socioeconomic status(SES)and depression of Chinese older adults through the mediating role of digital participation and health lifestyle.Methods:Using the nationally representative data from the China Family Panel Studies in 2020,4 846 participants aged 60 years and older were analyzed in our study.We explored the potential mechanisms of the relationship between SES and depression of Chinese older adults in the digital era through a chain multiple mediating effects model.The KHB(The Karlson,Holm,and Breen)method was used to analyze the mediating role of digital participation and health lifestyle and the propor-tion of mediating effect between the two was also calculated.A series of robustness tests were further con-ducted and the fit of the model was checked by structural equation modeling.Results:The mean age of the 4 846 older adults included in this study was(68.20±5.07)years,48.06％of whom were female and 51.94％were male.The KHB results showed that both digital participation and health lifestyle could mediate the relationship between SES and depression of older adults(P＜0.000 1)and the mediating role of health lifestyle accounted for a greater proportion than digital participation.And our study mainly found three potential pathways of SES and depression of older adults,including:(1)SES → digital par-ticipation → health lifestyle → depression,(2)SES → health lifestyle → depression,and(3)SES →depression.Structural equation modeling tests proved the overall fit of the model in this study.Conclu-sion:Our findings showed that in the digital age,in addition to the direct relationship between SES and depression of older adults,and the health lifestyle as a mediator between the relationship,there is also a sequential mediating role of digital participation and health lifestyle to reduce the risk of depression.The findings suggest that we should pay more attention to the probability of the digital divide exacerbating health inequalities and socioeconomic inequalities accumulation in the digital age and promote the co-progress of digital literacy and health literacy among older adults.

Objective To investigate the effects of clopidogrel on behavioral,content of inflamma-tory cytokines,and microglial in mice with comorbidity of pain and depression.Methods Twenty-four male pathogen-free C57BL/6J mice,aged 8 weeks,weighing 23-27 g,were selected.The mice were randomly divided into three groups:sham group(group C),spared nerve injury(SNI)group(group S),and SNI+clopidogrel group(group L),8 mice in each group.The surgical procedure in group C was consistent with the SNI model,but the nerve and maintained nerve integrity were not damaged.Group S was prepared with the SNI model,and group L was given clopidogrel 10 mg/kg since 21 days after the SNI model was prepared for 14 days continuously.Mechanical withdrawal threshold(MWT)was detected 1 day before surgery,7,14,21,28,and 35 days after surgery.The tail suspension test(TST)and forced swim test(FST)were performed 35 and 37 days after surgery,and the motionless time was calculated.Then the mice were killed,and the right hippocampal tissue was harvested to detect the concentration of IL-1β,IL-6,and TNF-α by enzyme-linked immunosorbent assay(ELISA),the expression of IL-1β,IL-6,and TNF-α mRNA by reverse transcription-polymerase chain reaction(RT-PCR),and the number of microglia by immunofluores-cence staining.Results Compared with group C,MWT were significantly decreased 7,14,21,28,and 35 days after operation,the immobility time of TST and FST were significantly prolonged,the concentrations and mRNA expressions of IL-1β,IL-6,and TNF-α were significantly increased,and the number of micro-glia were significantly increased in groups S and L(P＜0.05).Compared with group S,MWT were signifi-cantly increased 28 and 35 days after operation,the immobility time of TST and FST were significantly short-ened,the concentrations and mRNA expressions of IL-1β,IL-6,and TNF-α were significantly decreased,and the number of microglia was significantly reduced in group L(P＜0.05).Conclusion Clopidogrel can reduce the concentrations and mRNA expressions of IL-1β,IL-6,and TNF-α,inhibit the inflammatory reaction,reduce the number of activated microglia,and improve the and chronic neuropathic pain and de-pression in mice with comorbidity of pain and depression.

Objective:To investigate the levels of chemokine 2 (CCL2), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X3-C motif) ligand 1 (CX3CL1), and chemokine (C-X-C motif) ligand 10 (CXCL10) in the cerebrospinal fluid of patients with acute and chronic herpes zoster (HZ), and their correlation with the severity of neuropathic pain.Methods:A total of 60 patients with acute herpes zoster and postherpetic neuralgia (PHN) treated at the First Affiliated Hospital of Zhengzhou University from November 2022 to November 2023 were selected for a case-control study. These patients were divided into a HZ group ( n = 25) and a PHN group ( n = 35). The pressure pain threshold in the affected area was measured on the day of admission for all patients. The Visual Analogue Scale scores were evaluated in both groups. After lumbar puncture, 2 mL of cerebrospinal fluid was collected, and the levels of related chemokines in the cerebrospinal fluid were detected using the enzyme-linked immunosorbent assay. Results:In the HZ group, the levels of chemokines CXCL1 and CXCL10 were (24.84 ± 6.97) ng/L and (107.46 ± 28.29) μg/L, respectively, while in the PHN group, they were (20.51 ± 3.16) ng/L and (132.98 ± 30.92) μg/L. The differences in the levels of chemokines CXCL1 and CXCL10 between the two groups were statistically significant ( t = 2.91, -3.26, both P < 0.05). There were no statistically significant differences in the levels of chemokines CCL2 and CX3CL1 between the two groups ( t = 1.62, -0.23, both P > 0.05). The levels of CCL2, CXCL1, CX3CL1, and CXCL10 in both groups were negatively correlated with the pressure pain threshold (HZ group: r = -0.84, -0.78, -0.93, -0.86; PHN group: r = -0.71, -0.78, -0.94, -0.76, all P < 0.01). Conclusion:Higher levels of chemokines in the cerebrospinal fluid of patients with acute and chronic HZ are associated with more pronounced neuropathic pain. The neuro-immune inflammation involving chemokines may be correlated with the severity of neuropathic pain in acute and chronic HZ.

Objective:To investigate the mechanism of curcumin affecting HIV-1 infection co-receptor CCR5 by regulating transcription factor FOXP3.Methods:Binding sites of transcription factor FOXP3 on CCR5 promoter were predicted and analyzed by bioinformatics method.AutoDock 4.2 software was used to connect curcumin and FOXP3 flexibly.MTT assay was used to detect cyto-toxcity of curcumin on activity of Jurkat cells.qRT-PCR and Western blot were used to detect expression levels of CCR5 and FOXP3 mRNA and protein in Jurkat cells that were treated with different concentrations of curcumin.pcDNA3.1-FOXP3 expression vector was built and combined with the prediction results of transcription factors.The mutant CCR5 gene fragment was amplified by Overlap PCR,and the mutant CCR5 promoter recombinant vector pFireRluc-Mt-CCR5 was constructed.Binding site between transcription fac-tor FOXP3 and CCR5 promoter was verified by double luciferase reporter gene assay.Results:Results of JASPAR transcription factor prediction showed that there was a binding site between CCR5 promoter and transcription factor FOXP3;molecular docking results showed that curcumin could bind to the active region of FOXP3;MTT results showed that curcumin inhibited the activity of Jurkat cells after 24 hours,and the IC50 was 34.48 μmol/L.qRT-PCR and Western blot showed that expression levels of CCR5 and FOXP3 mRNA and protein were decreased in a dose-dependent manner after different concentrations of curcumin treated Jurkat cells;double luciferase reporter gene confirmed that FOXP3 could bind to CCR5 promoter,and the transcription factor FOXP3 could regulate the activity of CCR5 promoter;results of the recovery experiment of FOXP3 on curcumin showed that when the curcumin concentration was 60 μmol/L,relative value of luciferase activity in HEK293T cells with pcDNA3.1-FOXP3 and pFireRluc-Wt-CCR5 was signifi-cantly higher than that in pFireRluc-Wt-CCR5+curcumin-60 group(P<0.01).Conclusion:FOXP3 can regulate the activity of CCR5 promoter,and the mechanism may be that curcumin affects activity of CCR5 promoter by acting on binding site of FOXP3 and CCR5 promoter.

Objective:To evaluate the role of spinal cord neuron Src-associated-in-mitosis-68-kDa (SAM68)-transient receptor potential vanilloid-1 channel (TRPV1) signaling pathway in diabetic neuropathic pain (DNP) in mice.Methods:Forty SPF male C57BL/6 mice, aged 8 weeks, weighing 18-22 g, were used in this study. Diabetes mellitus was induced by intraperitoneal streptozotocin 0.12 mg/g, and successful DNP model was defined as decrease in the mechanical paw withdrawal threshold (MWT) of the hind limb≥50% of the baseline value. Twenty-four mice with DNP at 4 weeks after developing the model were divided into 3 groups ( n=8 each) using a simple random sampling: DNP group, SAM68 knocked down group (KD group) and virus control group (VC group). Eight diabetic mice with decrease in MWT <50% were randomly selected as non-DNP group (ND group), and 8 normal mice were randomly selected as control group (NC group). At 4 weeks after developing the diabetes mellitus model, SAM68 gene silencing virus and empty virus were injected into the lumbar enlargement of the spinal cord in KD group and VC group, respectively. MWT was measured before developing the diabetes mellitus model and at 4 and 6 weeks after developing the diabetes mellitus model. The mice were sacrificed after the end of MWT measurement at week 6 after developing the model, spinal cord tissues were collected and the expression of SAM68 and TRPV1 was detected by Western blot, and their localization in the spinal cord was observed by immunofluorescence. Results:Compared with NC and ND groups, the MWT was significantly decreased at 4 and 6 weeks after developing the model, and the expression of SAM68 and TRPV1 in spinal cord tissues was up-regulated in DNP group ( P<0.05). Compared with DNP group, the MWT was significantly increased at 6 weeks after developing the model, the expression of SAM68 and TRPV1 in spinal cord tissues was down-regulated, and no significant change was found in the parameters mentioned above in VC group ( P>0.05). SAM68 and TRPV1 were expressed in neurons in the same region of the spinal cord. Conclusions:Activation of SAM68-TRPV1 signaling pathway in spinal cord neurons is involved in the pathophysiological mechanism of DNP in mice.

Objective:To evaluate the role of lactate-induced mitochondrial division of spinal cord neurons in diabetic neuropathic pain (DNP) in mice.Methods:Thirty-six SPF-grade healthy adult male C57BL/6 mice, aged 2 months, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (CON group), DNP group, and DNP+ sodium oxalate group (OXA group). The diabetic model was established by intraperitoneal injection of streptozotocin 130 mg/kg. After the diabetic model was successfully established, sodium oxalate 750 mg/kg was intraperitoneally injected once a day for 4 consecutive weeks to inhibit lactate production in OXA group, while the equal volume of normal saline was given instead at the same time in C group and DNP group. The mechanical paw withdrawal threshold (MWT) of the left hindpaw was measured before developing the model and at 1, 2, 3 and 4 weeks after developing the model. After completing the last behavioral testing, the spinal cord tissue of the lumbar segment (L 4-6) was taken for determination of the levels of lactate in serum and spinal cord tissues (by the colorimetric method), expression of the mitochondrial membrane potential, reactive oxygen species (ROS) content (using JC-1 or DHE probes), expression of mitochondrial dynamin-related protein 1 (Drp1) and mitochondrial protein mitofusin 2 (Mfn2) (by Western blot), and co-expression of Drp1 and neuronal neuronal marker neuronal nuclear protein (NeuN) (by immunofluorescence double labeling) and for examination of the structure and the number of mitochondria (with a transmission electron microscope). Results:Compared with C group, the MWT was significantly decreased after developing the model, the levels of lactate in serum and spinal cord tissues and ROS content in the spinal cord were increased, the mitochondrial membrane potential was decreased, the Drp1 expression was up-regulated, the Mfn2 expression was down-regulated, the number of mitochondria was increased, the area was reduced ( P<0.05), and the co-expression of Drp 1 and NeuN was increased in DNP group and OXA group. Compared with DNP group, the MWT was significantly increased after developing the model, the levels of lactate in serum and spinal cord tissues and ROS content in the spinal cord were decreased, the mitochondrial membrane potential was increased, the Drp1 expression was down-regulated, the Mfn2 expression was up-regulated, the number of mitochondria was decreased, the area was increased ( P<0.05), and the co-expression of Drp 1 and NeuN was decreased in OXA group. Conclusions:Lactate-induced excessive mitochondrial division of spinal cord neurons can lead to mitochondrial dysfunction, which may be involved in the maintenance mechanism of DNP in mice.

ObjectiveTo characterize a cluster epidemic of coronavirus disease 2019 （COVID-19）on campus in Baotou city and provide evidence for the prevention and control of COVID-19 in universities. MethodsField epidemiological investigation was conducted to determine the confirmed cases and close contacts in the cluster epidemic of COVID-19 in a university of western China in 2022. Descriptive analysis was utilized to illustrate the epidemic timeline and schematic diagram. Real-time quantitative fluorescent PCR（RT-PCR） was used to detect the nucleic acid of SARS-CoV-2 in the collected samples. ResultsA total of eight students were infected in the cluster epidemic on campus， including 2 confirmed cases and 6 asymptomatic cases. Case A1 infected other 7 students in the same dormitory or on the same floor by close contact. After a 10-day quarantine and medical observation， no further case was reported. The overall incidence rate was 1.22% and the incidence rate among close contacts was 2.24%. ConclusionThis cluster epidemic of COVID-19 is characterized by strong and fast transmission. Repeated contact with no personal protection in confined space is highly vulnerable to cluster epidemic. Prevention of cluster epidemics on campus remains crucial to contain the epidemic. Therefore， it is necessary to strengthen the management of campus containment， interrupt the transmission route， identify close contacts and implement quarantine management as early as possible to avoid the cluster epidemics on campus.