Objective:To study the regulatory mechanism of p38 MAPK signaling pathway participate in hyperalge-sia reaction in Parkinson's disease(PD)rats model induced by 6-hydroxy dopamine(6-OHDA).Methods:Forty male Sprague Dawley(SD)rats were randomly divided into four groups:Sham group(Sham),model group(6-OHDA),p38 MAPK inhibitor SB203580 treatment group(6-OHDA+SB203580)and p38 MAPK activator anisomycin(ANS)treatment group(6-OHDA+ANS).PD model was established by intra-striatal injection of 6-OHDA stereotactically.6-OHDA+SB203580 and 6-OHDA+ANS groups was injected with 6-OHDA to establish PD model,and treated with inhibitor SB203580 or activator ANS respectively.The von Frey hairs were applied to measure the mechanical paw with-draw threshold(PWT)of rats.Enzyme linked immunosorbent assay(ELISA)was used to detect the content of IL-6,IL-1β,and TNF-α in rat dorsal root ganglion(DRG).The mRNA levels of genes IL-6,IL-1β,TNF-α,and p38 MAPK in rat DRG was detected by real time RT-PCR.Results:In the DRG of 6-OHDA included PD rats,the expres-sion levels of IL-6,IL-1β,TNF-α,and p38 MAPK were significantly increased(P＜0.05),and the PWT of rats were significantly decreased(P＜0.05).The application of activator ANS further increased the expression levels of IL-6,IL-1β,TNF-α,and p38 MAPK,and the PWT of rats were decreased.After application of inhibitor SB203580,the ex-pression levels of IL-6,IL-1β,TNF-α and p38 MAPK were significantly decreased in the DRG of rats(P＜0.05),and the PWT were significantly increased in rats(P＜0.05).Conclusion:6-OHDA induces mechanical hyperalgesia reaction in rats,and the molecular mechanism is related to activation of the p38 MAPK signalling pathway.

Objective:To explore the combination of high risk screening and family screening for potential patients with Fabry disease in adult hemodialysis population, and to improve the diagnostic efficiency of the disease.Methods:It was a cross-sectional investigation study. High-risk screening for Fabry disease was performed on adult hemodialysis patients with end-stage kidney disease who were admitted to Yongkang First People's Hospital of Zhejiang Province between November 2022 and February 2023. Dry blood paper α-galactosidase A (α-Gal A) detection assay was performed in males, or glycosphingolipids (Lyso-GL-3) detection assay was performed in females. GLA genetic assay was performed for further diagnosis after abnormal screening results. Family screening was carried out on the family members of the confirmed Fabry disease patients, and α-Gal A activity and Lyso-GL-3 of peripheral blood were measured. Additionally, urine routine, blood biochemistry, eye examination, hearing test, cranial magnetic resonance imaging, and electrocardiogram were performed to assess organ damage. Results:Among 244 hemodialysis patients, 139 (56.97%) were males and 105 (43.03%) were females. The age ranged from 25 to 81 years (with median age of 61 years). One female patient with Fabry disease was identified GLA IVS4+919G>A mutation, resulting in a total prevalence of 0.41%. Pedigree screening was conducted on 41 family members of the patient, leading to the confirmation of 12 patients (including the proband), including 3 males and 9 females. Among them, 9 patients were abnormal in enzyme examination, 10 patients were abnormal in substrate, and 11 patients were abnormal in gene sequencing. None of the 12 patients exhibited limb pain, hypohidrosis, angiokeratoma, corneal opacity, and hearing impairment. Eight patients had heart abnormalities. Nine patients had abnormal urine routine (albuminuria or hematuria) and one patient had abnormal renal function. Four patients had abnormal cranial magnetic resonance imaging findings. Conclusions:One GLA IVS4+919G>A mutation family is successfully identified through the combination of high-risk screening and family screening in adult hemodialysis patients, with a total of 12 cases of Fabry disease. The combination of high-risk screening and family screening proves to be effective in detecting potential patients with Fabry disease, and improve the screening efficiency of Fabry disease.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

To explore the potential associations between perceived stress and health-promoting behaviors based on the theoretical schema of the middle-range theory of adaptation to chronic illness. From January to May 2021, a convenience sampling method was used to recruit 230 young and middle-aged patients with metabolic syndrome who underwent physical examination in the inpatient center of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. The Health-Promoting Health Profile-Ⅱ, Chinese Perceived Stress Scale, Coping and Adaptation Processing Scale-Short Form, and Multi-dimensional Scale of Perceived Social Support were used in the cross-sectional study. The chain mediation effect procedure and bootstrap sampling test were used to examine the mediating role of adaptability and social support between perceived stress and health-promoting behaviors. The mean score of health-promoting behaviors was 100.0±14.6, the mean score of perceived stress was 22.0± 6.9, the mean score of adaptability was 47.0±6.1, and the mean score of social support was 63.8±10.8. Perceived stress had a negative impact on patients' health-promoting behaviors (=-0.309, <0.05). The adaptability (effect size= -0.112, 95%:-0.199~-0.038) and social support (effect size= -0.032, 95%:-0.083~played a mediating role and a chain mediating role in the process of perceived stress influencing patients' health-promoting behaviors (effect size= -0.045, 95%:-0.093~-0.020). Adaptability and social support play an intermediary role between perceived stress and health-promoting behaviors in young and middle-aged patients with metabolic syndrome. Healthcare professionals can motivate patients to develop healthy behaviors by developing intervention strategies on adaptability and social support.
Adaptation, Psychological ; Cross-Sectional Studies ; Humans ; Metabolic Syndrome ; Middle Aged ; Social Support ; Stress, Psychological

Objective:To compare the clinical features, clinical efficacy, and prognosis of patients with double-hit and non-double-hit high-risk multiple myeloma (MM) and explored the clinical significance of high-risk cell karyotype in MM development.Methods:The clinical data of 73 high-risk MM patients admitted to the Department of Hematology of Fujian Provincial Hospital from January 2011 to February 2019 were retrospectively analyzed. Interphase fluorescence in situ hybridization was used to detect their karyotypes. Based on mSMART 3.0 risk stratification, we divided the patients into a double-hit group (28 cases) and a non-double-hit group (45 cases).Results:Fifteen patients in the double-hit group and 26 in the non-double-hit group received bortezomib-based chemotherapy. The median progression-free survival (PFS) in the double-hit and the non-double-hit groups was 8.0 months and 22.0 months, and the median overall survival (OS) was 10.0 months and not reached, respectively. Ten patients in the double-hit group and 12 in the non-double-hit group received bortezomib combined with lenalidomide (RVD) chemotherapy. The median PFS in the double-hit group and the non-double-hit group was 12.0 months and 24.0 months, and the median OS was 14.0 months and not reached, correspondingly. Both the PFS and OS of the double-hit group were significantly shorter than those of the non-double-hit group ( P<0.05). Univariate analysis results indicated that cytogenetic abnormalities, revised-international staging system (R-ISS), β2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients ( P<0.05). The cytogenetic abnormalities, R-ISS, and β2 microglobulin were associated with OS in high-risk MM patients ( P=0.001). Multivariate Cox regression analysis showed that the cytogenetic grouping was an independent prognostic factor for OS and PFS in high-risk MM patients. The risk of disease progression was 3.160 times (95% CI: 1.364-7.318) and the risk of death was 2.966 times higher (95% CI: 1.205-7.306) in the double-hit group than those in the non-double-hit group. Calcium was an independent risk factor for PFS in the high-risk MM patients. Notably, the risk of disease progression in patients with calcium levels≥ 2.75 mmol/L was 2.667 times higher than that in patients with calcium<2.75 mmol/L (95% CI: 1.209-5.883). Conclusions:Double-hit patients are a highly specific group with worse high-risk MM prognosis. In such patients, the relapse is more common, the disease progression is faster, and the survival time is shorter than those in the non-double-hit patients.

Objective:To compare the clinical features, clinical efficacy, and prognosis of patients with double-hit and non-double-hit high-risk multiple myeloma (MM) and explored the clinical significance of high-risk cell karyotype in MM development.Methods:The clinical data of 73 high-risk MM patients admitted to the Department of Hematology of Fujian Provincial Hospital from January 2011 to February 2019 were retrospectively analyzed. Interphase fluorescence in situ hybridization was used to detect their karyotypes. Based on mSMART 3.0 risk stratification, we divided the patients into a double-hit group (28 cases) and a non-double-hit group (45 cases).Results:Fifteen patients in the double-hit group and 26 in the non-double-hit group received bortezomib-based chemotherapy. The median progression-free survival (PFS) in the double-hit and the non-double-hit groups was 8.0 months and 22.0 months, and the median overall survival (OS) was 10.0 months and not reached, respectively. Ten patients in the double-hit group and 12 in the non-double-hit group received bortezomib combined with lenalidomide (RVD) chemotherapy. The median PFS in the double-hit group and the non-double-hit group was 12.0 months and 24.0 months, and the median OS was 14.0 months and not reached, correspondingly. Both the PFS and OS of the double-hit group were significantly shorter than those of the non-double-hit group ( P<0.05). Univariate analysis results indicated that cytogenetic abnormalities, revised-international staging system (R-ISS), β2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients ( P<0.05). The cytogenetic abnormalities, R-ISS, and β2 microglobulin were associated with OS in high-risk MM patients ( P=0.001). Multivariate Cox regression analysis showed that the cytogenetic grouping was an independent prognostic factor for OS and PFS in high-risk MM patients. The risk of disease progression was 3.160 times (95% CI: 1.364-7.318) and the risk of death was 2.966 times higher (95% CI: 1.205-7.306) in the double-hit group than those in the non-double-hit group. Calcium was an independent risk factor for PFS in the high-risk MM patients. Notably, the risk of disease progression in patients with calcium levels≥ 2.75 mmol/L was 2.667 times higher than that in patients with calcium<2.75 mmol/L (95% CI: 1.209-5.883). Conclusions:Double-hit patients are a highly specific group with worse high-risk MM prognosis. In such patients, the relapse is more common, the disease progression is faster, and the survival time is shorter than those in the non-double-hit patients.

Objective:To explore the application effect of sustainable skin-stretching device in scalp and soft tissue defect.Methods:From June 2017 to January 2020, 5 patients (3 males and 2 females, aged 31-57 (38.0±2.1) years) with large area of scalp and soft tissue defect and skull exposure were admitted to Department of Reparative and Reconstructive Surgery of the Second Hospital of Dalian Medical University. The wound area ranged from 16.0 cm×8.0 cm to 18.0 cm×12.0 cm. The sustainable skin-stretching device was installed after debridement operation for scalp wound. The wound was stretched from the 3rd day after installation of the device, at a basic speed of 1 mm/d and finished for 3 times on average. During stretching, close attention was paid to the changes in blood flow of the wound margin and the subjective feeling of the patients. When the result was negative in the squeezing and pinching test for wound margin after stretching, the further stretching was stopped, the final stretching state was maintained for 3 days, and the wounds were sutured directly. The wound healing during stretching of sustainable skin-stretching device and the occurrence of complications were observed. The rest wound areas after stretching for 5, 10, 15, and 20 days were measured. The wound healing and hair growth were observed during follow-up.Results:All the wounds of 5 patients was sutured directly after stretching for 19-23 d. There was no tension blister on the margin of wounds during stretching, and the margin of wounds healed well after being sutured without skin necrosis. After stretching treatment for 5-20 d, the wound areas were gradually decreased. During follow-up of 2-11 (4.5±1.5) months, the elasticity, color, feeling, and regenerated hair growth of the stretched scalp tissue were close to those of the surrounding normal skin tissue. The linear scar formed on the margin of wounds, but no scar formed on the wounds.Conclusions:The application of sustainable skin-stretching device can reduce the difficulty in repairing scalp and soft tissue defect, with the regenerated hair growing well after treatment, which is worthy of clinical promotion.

Objective To compare the neuropsychological features and other clinical and imaging characteristics among patients with typical Alzheimer's disease (TAD),frontal variant Alzheimer's disease (fvAD) and behavioral variant frontotemporal dementia (bvFTD).Methods Neuropsychological scales were used to evaluate the cognitive function and neuropsychiatric symptoms of nine patients with fvAD,30 patients with bvFTD and 32 patients with typical AD (TAD).The apolipoprotein E (ApoE) ε4 allele and brain imaging techniques,including the magnetic resonance imaging (MRI),11 C-Pittsburgh compound B positron emission tomography (PIB-PET),and 18F-deoxyglucose positron emission tomography (FDG-PET),were used for the differential diagnosis of fvAD and bvFTD.Results There were no significant differences in general cognitive function or daily activity in patients among the three groups.However,the cognitive subscale scores of Montreal Cognitive Assessment (MoCA) scale,including visual acuity and executive function,delayed recall,and orientation,were significantly different among the groups (Z =7.891,P =0.035;Z =7.412,P =0.031;Z=6.437,P=0.043,respectively).The clock drawing test (CDT) score of TAD group was higher than that in the bvFTD and fvAD groups (Z=8.673,P=0.020),while the neuropsychological questionnaire (NPI) scores of the bvFTD and fvAD groups were higher than those of the TAD group (Z=7.577,P =0.023).Meanwhile,the incidences of agitation,disinhibition and abnormal behavior of NPI in the bvFTD and fvAD groups were higher than those in the TAD group (x2 =11.139,P =0.004;x2 =6.481,P =0.039;x2 =6.812,P =0.033,respectively).The frequencies of the ApoE ε4 allele were 44.4％ in the fvAD group and 33.3％ in the bvFTD group,which were not significant different from that in the TAD group (40.6％).Furthermore,patients in the fvAD group were associated with decreased regional cerebral glucose metabolism and amyloid deposition in the temporalparietal cortex evaluated by FDG-PET and PIP-PET.Conclusions Neuropsychological evaluation is valuable for the differential diagnosis of TAD,fvAD and bvFTD.The frequencies of the ApoEε4 allele are similar among the three groups.FDG-PET and PIB-PET imaging plays an important role in the diagnosis of variant types of Alzheimer's disease.

Objective To assess the interference by calcium dobesilatein 7 peroxidase-baseduric acid assays and to determine its clinical significance.Methods In the in vitro experiments, uric acid in pooled serum with final concentrations of calcium dobesilate additions (0, 2, 4, 8, 16, 32, and 64μg/ml) were measured by 7 peroxidase-based assays.Percent Bias (%) was calculated relative to the drug-free specimen.In the in vivo experiments, changes in serum uric acid and calcium dobesilate concentrations were observed before and after calcium dobesilate administration ( baseline, 0 h, 1 h, 2 h, 3 h, 4 h, 6 h ) involunteers.The interference in different assays was assessed compared with LC-IDMS/MS method. Calcium dobesilate levels in 40 specimens from those taking calcium dobesilate were measured by HPLC method.Of the 40 specimens, 10 were selected to analyse the levels of uric acid by both peroxidase and UV measurement method to assess the impact in clinical status.Results In the in vitro study, concentrations of uric acid measured by 7 peroxidase-based assays were reduced by -6.3%to -21.2%compared with drug-free serum, when theconcentration of calcium dobesilate was16μg/ml.In the in vivo study, comparedto UA levels at 0 h, the biasesof serum uric acid determined by peroxidase method after calcium dobesilate administration(1 h, 2 h, 3 h, 4 h, 6 h) were of -3.33%, -6.79%, -7.49%, -6.07%, -4.09%, respectively.The observed uric acid concentrations for 8 participants measured by enzymatic assays were inhibited by -3.75% to -6.89% at 0 hour and by -16.9% to-22.22% at 2 hours relative to the concentrations measured by the LC-IDMS/MS method. Conclusions Calcium dobesilate produced a clinically significant negative interference with uric acid in all peroxidase-based uric acid assays,which may result in false evaluation of uric acid level in clinical status.Significant differences in the degree of interference were observed among the assays.