Objective To investigate the relationship between white matter lesions(WML) and cognitive impairment in migraine with and without aura.Methods 56 migraine without aura patients (MwoA group),22 migraine with aura patients(MA group) and 30 normal controls were recruited.All of them were performed head MRI examination and were evaluated by operational definitions of ARWMC and Mattis Dementia Ratiing Scale(DRS),and compare among three groups,discuss the relationship between WML and cognitive impairment.Results (1) Compared with control group,the occurrence rate of WML in MA group was significantly higher(40.9％ vs 13.3％,x2=22.74,P＜0.01).The OD-ARWMC score was significantly higher in both MA and MwoA groups((0.73±l.12) vs (0.13±0.35),t=2.76,P＜0.01;(0.36±0.67) vs (0.13±0.35),t=1.75,P＜0.05).Compared with MwoA group,the occurrence rate of WML and the OD-ARWMC score of MA group was significantly higher(t=22.80,P＜0.01;t=1.79,P＜0.05).(2) During the attack period,the DRS total scale and its 5 factors (attention,initiation/perseveration,concept formation,construction and memory) were significantly lower in both MwoA and MA group(P＜0.05 or 0.01) than control group,while the DRS total scale and its two factors (attention,concept formation) of MA group were significantly lower than that of MwoA group (P＜ 0.01).During the intermission period,the concept formation and memory scale in MA group was significantly lower than control group(P＜0.05),only memory factor in MwoA group was significantly lower than control group(P＜0.05),while the initiation/perseveration factor scale of MA group was significantly lower than MwoA group(P＜0.05).(3) There Was a negative correlation between OD-ARWMC scale and the total DRS scale as well as its three factors (attention,concept formation,memory)during attack period in MA group(r=-0.584,P＜0.01;r=-0.465,P＜0.05;r=-0.558,P＜0.01;r=-0.439,P＜0.05).There was a negative correlation between OD-ARWMC scale and the total DRS scale as well as concept formation factor during attack period in MwoA group (r=-0.328,P＜ 0.05;r =-0.276,P＜ 0.05).Conclusion Migraine patients may have white matter lesions and cognitive impairment,especially in MA patients and during attack period.

Objective:To investigate the clinical efficacy and safety of gabapentin or topiramate combined with venlafaxine in the treatment of chronic migraine patients with generalized anxiety disorder.Methods:From June 2018 to February 2020, 127 patients with chronic migraine complicated with generalized anxiety disorder in the Second Affiliated Hospital of Guangxi Medical University were selected. The patients were divided into gabapentin combined with venlafaxine group (observation group, 64 cases) and topiramate combined with venlafaxine group (control group, 63 cases) according to the random number table method, and all patients were treated for 6 months. The headache attack days per month, headache visual analogue scale (VAS), migraine specific quality of life questionnaire V2.1 (MSQ V2.1), headache impact measurement-6 (HIT-6) score, Pittsburgh sleep quality index (PSQI) score were recorded before treatment and 3 and 6 months after treatment.Results:In observation group, 57 cases completed 3 months of treatment, and 53 cases completed 6 months of treatment. In the control group, 56 cases completed 3 months of treatment, and 50 cases completed 6 months of treatment. The headache attack days per month, headache VAS, HIT-6 and PSQI 3 and 6 months after treatment in 2 groups were significantly lower than those before treatment, observation group: (16.31 ± 5.02) and (15.69 ± 6.31) d vs. (22.62 ± 3.27) d, (3.67 ± 1.60) and (1.91±1.05) scores vs. (5.09 ± 1.43) scores, (49.34 ± 11.01) and (47.34 ± 9.05) scores vs. (60.25 ± 11.61) scores, (10.09 ± 2.81) and (9.68 ± 2.74) scores vs. (13.50 ± 2.81) scores; control group: (14.58 ± 7.37) and (9.92 ± 5.07) d vs. (23.05 ± 5.24) d, (4.74 ± 1.15) and (3.16 ± 1.60) scores vs. (5.90 ± 2.06) scores, (42.77 ± 8.02) and (40.09 ± 9.72) scores vs. (59.37 ± 9.08) scores, (9.66 ± 2.71) and (8.62 ± 2.07) scores vs. (14.61 ± 2.79) scores, and there were statistical differences ( P<0.05). The headache VAS 3 and 6 months after treatment in observation group was significantly lower than that in control group, and there was statistical difference ( P<0.05). The functional limitations, function loss, emotional function scores and total score of MSQ V2.1 3 and 6 months after treatment in 2 groups were significantly lower than those before treatment, observation group: (17.62 ± 9.81) and (16.01 ± 5.73) scores vs. (36.96 ± 9.55) scores, (12.17 ± 5.60) and (11.09 ± 3.27) scores vs. (17.06 ± 6.08) scores, (8.42 ± 2.17) and (8.94 ± 1.90) scores vs. (11.40 ± 4.09) scores, (33.24 ± 9.61) and (28.62 ± 5.04) scores vs. (62.75 ± 14.02) scores; control group: (17.08 ± 8.73) and (16.79 ± 5.19) scores vs. (36.82 ± 9.68) scores, (9.04 ± 4.48) and (8.90 ± 3.46) scores vs. (17.26 ±6.01) scores, (6.92 ± 2.61) and (5.15 ± 1.74) scores vs. (11.30 ± 5.47) scores, (31.65 ± 9.17) and (30.66 ± 6.04) scores vs. (62.91 ± 11.18) scores, and there were statistical differences ( P<0.05). There was no significant difference in the effective rate and the incidence of adverse drug reactions 3 and 6 months after treatment between 2 groups ( P>0.05). Conclusions:Gabapentin or topiramate combined with venlafaxine can reduce the degree of headache in chronic migraine patients with generalized anxiety disorder, reduce the number of headache days per month, improve sleep and improve the quality of life. However, the adverse reactions of gabapentin still need to be paid more attention.

Objective:To explore the value of symptom-oriented clinical lateral thinking training in gynecology internship teaching.Methods:We enrolled a total of 166 medical students of the five-year program of grades 2017 and 2018 who would participate in internships at the First Department of Gynecology of Renmin Hospital of Wuhan University. They were randomly divided into experimental group and control group, with 43 students of grade 2017 and 37 students of grade 2018 in the experimental group and 46 students of grade 2017 and 40 students of grade 2018 in the control group. The experimental group was taught using a symptom-oriented clinical lateral thinking training mode, and the control group was taught using a traditional teaching mode. At the end of the internship, the teaching quality was evaluated by means of an exam and satisfaction survey. The data were analyzed using the t test with the use of SPSS 24.0. Results:For both grades 2017 and 2018, the two groups had similar scores of theoretical knowledge, but the experimental group had significantly higher scores of medical history taking, physical examination, and medical record analysis compared with the control group ( P<0.05); for example, among students of grade 2017, the score of medical record analysis was (37.34±1.08) in the experimental group and (32.18±1.32) in the control group. The experimental group had significantly higher degrees of satisfaction than the control group in terms of doctor-patient communication ability, effective information acquisition ability, clinical case analysis ability, self-learning ability, literature search and review ability, team cooperation ability, and learning interest motivation (all P<0.05). Conclusions:The symptom-oriented clinical lateral thinking training mode can help students master the diagnosis and treatment principles of gynecological diseases, improve their abilities of clinical analysis, doctor-patient communication, effective information acquisition, self-learning, and literature search and review, and motivate their interest in learning.

Objective:To investigate the effect of pirfenidone (PFD) on the proliferation of human glomerular mesangial cells (HMC) stimulated by serum IgA1 in patients with IgA nephropathy (IgAN) and its possible mechanism.Methods:Serum IgA1 of IgAN patients was purified by Jacalin affinity chromatography combined with Sephacryl S-200 gel filtration, and then heated to aggregated form (aIgA1). CCK8 method was used to confirm the concentration and time of PFD. The cells were divided into blank control group, IgA1 (0.5 mg/ml) group and IgA1 (0.5 mg/ml)+PFD (2 mmol/L) group. The CCK8 method was used to detect proliferation of mesangial cells. The cell cycle was detected by flow cytometry, and the proliferation index of mesangial cells was calculated. The expression levels of transforming growth factor β1 (TGF-β1), Smad4, Smad7, fibronectin (FN) and collagen Ⅳ protein and mRNA were detected through Western blotting and real-time PCR.Results:Compared with blank control group, the proliferation of HMC was promoted significantly by aIgA1 ( P<0.05). After PFD treatment, the proliferation of HMC was significantly inhibited ( P<0.01). Compared with the blank control group, the number of G1 phase cells decreased, the number of S phase cells and cell proliferation index increased in IgA1 group (all P<0.05). Compared with IgA1 group, the number of cells in G1 phase increased significantly, the number of cells in S phase and G2/M phase decreased significantly, and the cell proliferation index decreased in IgA1+PFD group (all P<0.05). Western blotting and real-time PCR results showed that compared with the blank control group, the protein and mRNA expressions of collagen Ⅳ, FN and Smad4 in HMC stimulated by aIgA1 were significantly increased, while TGF-β1 protein expression was increased and Smad7 protein expression was decreased (all P<0.05). After PFD treatment, the protein and mRNA expression of collagen Ⅳ, FN and Smad4 in HMC was significantly decreased, while TGF-β1 protein expression was obviously decreased, and Smad7 protein was up-regulated (all P<0.05). There was no significant difference in the mRNA expression of TGF-β1 and Smad7 in each group before and after PFD treatment (all P>0.05). Conclusions:PFD can increase the arrest of HMC in G1 phase, inhibit the proliferation of HMC induced by aIgA1 of IgAN patients, and reduce the production of extracellular matrix. The mechanism may be related to up-regulation of Smad7 expression and down-regulation of TGF-β1/Smad4 pathway.

Objective To investigate the role and mechanism of SR8278,a synthetic antagonist of nuclear receptor subfamily 1 group D member 1(NR1D1),in alleviating the structural and functional impairment of the extraorbital lacrimal glands induced by jet lag in mice.Methods Totally 36 healthy wild C57BL/6J mice aged 8-10 weeks were randomly divid-ed into 3 groups(normal group,jet-lag group,and jet-lag+SR8278 group)after adapting to a circadian rhythm chamber under the 12 h light/12 h dark(12 h/12 h LD)cycle for 2 weeks,with 12 mice in each group.Mice in the normal group were fed in a circadian rhythm chamber in a 12 h LD cycle,mice in the jet-lag group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule,and mice in the jet lag+SR8278 group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule and received 25 mg·kg-1 SR8278.At the end of 5 days of intervention,locomotor activity,core body temperature and tear secretion of mice in each group were collected,and the weight of lacrimal gland tissues and size of lacrimal gland cells were measured.Immunohistochemical methods were used for histological evaluation of the extraor-bital lacrimal glands in mice.Lacrimal ribonucleic acid(RNA)was extracted for high-throughput RNA-sequencing analysis containing NR1D1,and the obtained transcriptomic data were used for KEGG and GO functional enrichment analysis.Re-sults Compared with the normal group,the jet-lag group had higher daytime activity,lower nighttime activity,higher daytime core body temperature,and lower nighttime core body temperature,with statistically significant differences(all P＜0.05).Compared with the jet-lag group,the jet-lag+SR8278 group had lower daytime activity,higher nighttime activi-ty,lower daytime core body temperature,and higher nighttime core body temperature,with statistically significant differ-ences(all P＜0.05).Compared with the normal group,the jet-lag group showed a decrease in lacrimal gland weight and tear secretion and an increase in size of lacrimal gland cells,with statistical significance(all P＜0.05);compared with the jet-lag group,the jet-lag+SR8278 group had an increase in lacrimal gland weight and tear secretion and a decrease in size of lacrimal gland cells,with statistical significance(all P＜0.05).Compared with the normal group,the jet-lag group showed a higher expression of NR1D1 in the lacrimal gland at night;compared with the jet-lag group,the jet-lag+SR8278 group showed a lower expression of NR1 D1 in the lacrimal gland at night(both P＜0.05).Bioinformatics analysis showed 947 significantly different genes in the jet-lag group and the jet-lag+SR8278 group,of which 43 are significantly upregulated genes,and 904 are significantly downregulated genes.The Notch signaling pathway has the most significant difference.Conclusion SR8278 effectively enhances the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition.This process may be completed through the Notch signaling pathway.