AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.

AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective:To explore the vigilant attention function and behavioral changes in sleep disordered breathing(SDB) children.Methods:Thirty SDB children (SDB group) and 30 normal children (control group) were selected from June 2022 to August 2023. All participants underwent continuous performance test(CPT-AX) (Go/Nogo) and behavioral test. The latency and amplitude of contingent negative variation(CNV) components under cue/uncue conditions in leads F3, Fz and F4 were measured. The t-test and Mann-Whitney U test were used to conduct statistical analysis by SPSS 25.0 software. Results:(1) There were no statistically significant differences in the number of correct responses, reaction time and number of false alarms between the SDB group and the control group (all P>0.05).(2) The latencies of cue-CNV in the SDB group(F3: 618.00(582.50, 644.50)ms, Fz: 603.00(579.50, 634.00)ms, F4: (606.87±25.07)ms) were longer than those in the control group(F3: (508.47±25.82)ms, Fz: 502.00(470.00, 520.50)ms, F4: 514.00(487.00, 536.50)ms) in leads F3, Fz and F4. The latency of cue-CNV of lead F4 in the SDB group was higher than that in the control group, and the difference was statistically significant ( P<0.05). The latencies of uncue-CNV in lead F3 and Fz in the SDB group were higher than those in the control group, and the differences were statistically significant (both P<0.05). Conclusion:SDB children have shown activation in the right brain area during attentional tasks, and the prolonged CNV latency may be a sensitive neuroelectrophysiological marker for early clinical assessment of vigilant attention dysfunction.

Objective:To explore the cognitive function characteristics of children with primary snoring (PS) and obstructive sleep apnea-hypopnea syndrome (OSAHS) using event-related potentials.Methods:From October 2020 to October 2022, 20 children with OSAHS, 20 children with PS, and 22 normal children were recruited for continuous performance task (CPT) and behavioral assessments. ERP and behavioral data were meticulously recorded, with measurements of N1, P2, N2, and P3 wave amplitudes and latencies at F3, Fz, and F4 electrode sites. Statistical analyses were conducted using one-way ANOVA and Kruskal-Wallis test via SPSS 25.0 software.Results:(1) Behavioural test: There was no statistically significant difference in terms of correct responses, response times, and false alarms among the three groups (all P>0.05). (2) F3 Lead: There were statistically significant differences in Go-P2 amplitude, Nogo-P2 amplitude, Nogo-P2 latency, Go-P3 amplitude, and Nogo-P3 latency among the three groups (all P<0.05). Specifically, the OSAHS group exhibited higher Go-P2 amplitude((15.03±5.12) μV vs (10.97±5.50)μV), Nogo-P2 amplitude((14.80±5.84) μV vs (9.67±4.79)μV), and Go-P3 amplitude((11.58±6.02) μV vs (7.49±4.89) μV) compared to the normal group. Additionally, the OSAHS and PS groups exhibited longer Nogo-P2 latency compared to the normal group((223.10±20.61) ms vs (208.00±23.09) ms, (230.60±13.61) ms vs (208.00±23.09) ms), as well as prolonged Nogo-P3 latency((459.20±34.26) ms vs (460.40±24.52) ms and (429.91±31.49) ms) (all P<0.05). Fz Lead: There were statistically significant differences in Go-N1, Go-P2, Nogo-P2, Go-P3, Nogo-N2 wave amplitudes, and Nogo-P3 latency among the three groups (all P<0.05). Compared to the normal group, the OSAHS group exhibited increased Go-P3 amplitude((9.07±5.68) μV vs (5.10±3.51) μV) and decreased Nogo-N2 amplitude((-8.80±5.97) μV vs (-12.84±4.86) μV). Moreover, both the OSAHS and PS groups had prolonged Nogo-P3 latency compared to the normal group((481.60±45.16) ms vs (435.13±28.17) ms and 484.00(443.50, 525.00) ms vs (435.13±28.17) ms) (both P<0.05). F4 Lead: There were statistically significant differences in Go-P2 and Nogo-P2 wave amplitudes among the three groups (all P<0.05). Compared to the normal group, the OSAHS group demonstrated increased Go-P2 amplitude((13.72±5.64) μV vs (9.70±4.59) μV) and Nogo-P2 amplitude((13.90±5.35) μV vs (9.64±3.74) μV) (both P<0.05). Conclusions:Both children with OSAHS and PS exhibit attentional cognitive impairments. However, children with OSAHS demonstrate more pronounced deficits in conflict monitoring, response inhibition, and executive functioning. The prolonged latency of the P3 wave serves as a sensitive electrophysiological marker for the early detection of neurocognitive impairment in children with sleep disordered breathing.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective To assess the impact of statins combined with sorafenib(SRF)therapy on survival outcomes in patients with metastatic renal cell carcinoma(mRCC).Methods Clinical data of mRCC patients treated in the 908th Hospital of the Joint Security Force from November 2019 to November 2023 were retrospectively analyzed.They were categorized into statin group and non-statin group according to whether they used statins or not,and the differences in the primary endpoint of overall survival(OS),secondary endpoints of progression-free survival(PFS),objective response rate(ORR),and disease control rate(DCR)were compared between the two groups.Results A total of 80 patients were included in the study,with 27 in the statin group and 53 in the non-statin group.There were no statistically significant differences in partial remission,stable disease,disease progression,and DCR between the two groups(P＞0.05);complete remission and ORR were significantly higher in the statin group than in the non-statin group(P＜0.05).Kaplan-Meier analysis showed that,compared with the non-statin group,the median PFS and OS of the statin group were prolonged,and the difference in median PFS between the two groups was statistically significant(P＜0.05).In terms of safety,the incidence of other adverse events was similar in both groups(P＞0.05).Conclusion Statins combined with SRF treatment regimen can improve ORR and DCR and prolong median PFS and OS in patients with mRCC.

Objective To explore the clinical efficacy of oxygen blowing combined with clostridium butyricum and bifidobacterium powders in neonatal diaper dermatitis(DD).Methods Data of neonatal DD patients admitted to the Department of Pediatrics of the Affiliated Hospital of Hangzhou Normal University from January 2019 to June 2021 were retrospectively analyzed.They were divided into the control group(oxygen blowing)and the experimental group(oxygen blowing combined with clostridium butyricum and bifidobacterium powders)according to whether or not they received clostridium butyricum and bifidobacterium powders treatment.The primary efficacy index of the study was the treatment efficiency,and the secondary efficacy indexes were the severity of DD(Neonatal Rash Scale score,DD score,and lesion area score),time to erythema resolution,time to vesicle resolution,and time to healing.Results A total of 99 patients were included in the study,with 42 in the experimental group and 57 in the control group.The treatment efficiency of the experimental group was significantly higher than that of the control group(P＜0.05).With regard to the severity of DD,the papule and pustule scores,dermatitis extent scores,erythema severity scores,skin damage scores and lesion area scores of the experimental group were significantly lower than those of the control group(P＜0.05);the proportions of moderate and severe syndrome in the experimental group were lower than those of the control group(P＜0.05).The time for erythema to subside,the time for vesicles to subside and the time for healing were shorter in the experimental group than in the control group(P＜0.05).Conclusion Oxygen blowing combined with clostridium butyricum and bifidobacterium powders can significantly improve the clinical effect of neonatal DD,but the specific mechanism still needs to be explored.