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.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

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:This study analyzed the expression of CD24 antigen on bone marrow plasma cells (BMPC) of patients with multiple myeloma (MM) and the predictive value of induction therapy.Methods:This clinical observational study utilized 258 MM patients samples treated at the Hematology Department of Beijing Jishuitan Hospital who met the inclusion criteria in the Department of Hematology, Capital Medical University, from August 12th, 2022 to February 1st, 2024. According to the different stages of the disease, patients were divided into three groups: 78 cases of Newly Diagnosed Multiple Myeloma(NDMM) (42 males and 36 females, aged 62±11), 56 cases of the relapse refractory group (34 males and 22 females, aged 64±9), and 124 cases of the disease remission group (68 males and 56 females, aged 62±10). Multiparameter flow cytometry (MFC) was used to detect the expression level of CD24 antigen on BMPC and the relationship between CD24 and MM disease status. The clinical data and test results of 78 NDMM patients at initial diagnosis were retrospectively analyzed, including gender, age, MFC detection of the positive expression rate of antigens (CD19, CD20, CD24, CD27, CD56), the results of efficacy evaluation after induction therapy, ISS staging, R-ISS staging, blood hemoglobin, β2-microglobulin, human serum albumin, serum creatinine, lactate dehydrogenas, correction of calcium, BMPC ratio, and the results of FISH. The patients were divided into a deep remission group [including complete remission (CR) and very good partial remission (VGPR)] with 43 cases and a non-deep remission group (non CR and VGPR) with 17 cases according to the difference of antigen positive expression rate after induction therapy. The differences of antigen expression on BMPC between the two groups were compared. Binary logistic regression was used to analyze the relationship between the expression of each antigen and the efficacy after induction therapy in patients, and the results showed that CD24 was more correlated with the achievement of deep remission after induction therapy than other antigens. Therefore, taking the positive expression rate of CD24 in NDMM patients at the initial diagnosis and deep remission after induction therapy as the research objects, the predictive value of CD24 for NDMM patients reaching deep remission after induction therapy was analyzed by using receiver operating characteristic curve (ROC), and the optimal cutoff value was obtained. NDMM was divided into two groups according to the cut-off value, and the differences between the two groups in clinical baseline data and prognostic indicators were compared.Results:The positive rates of plasma cell CD24 expression in the NDMM group, the relapse refractory group and the disease remission group were 2.18 (95% CI 0.08-81.85)%, 3.81 (95% CI 0.10-64.56)%, 8.74 (95% CI 0.79-95.55)% respectively. Compared with the disease remission group, the NDMM and relapse refractory group was lower ( Z=-7.889, -5.282, respectively, P<0.001). Univariate analysis showed that there was a significant difference in the positive expression rate of CD24 at initial diagnosis between the deep remission group and the non-deep remission group ( Z=-3.265, P<0.001), while there was no significant difference in CD19 ( Z=-0.271, P=0.787), CD20 ( Z=-0.205, P=0.837), CD27 ( Z=-0.582, P=0.560), and CD56 ( Z=-0.328, P=0.743) between the two groups. Binary logistic regression analysis showed that compared with other antigens [CD19 ( OR=1.045, 95% CI 0.975-1.120, P=0.217), CD20 ( OR=1.000, 95% CI 0.971-1.030, P=0.976), CD27 ( OR=0.997, 95% CI 0.977-1.016, P=0.734), CD56 ( OR=1.006, 95% CI 0.990-1.006, P=0.449)], the expression of CD24 ( OR=0.423, 95% CI 0.990-1.006, P=0.449) on BMPC in NDMM patients was most closely related to the achievement of deep remission was achieved after induction therapy. The lower the proportion of CD24 at the initial diagnosis was, the lower the probability of achieving deep remission after induction therapy was. The area under the curve (AUC) of CD24 in predicting deep remission after induction therapy was 0.772 (95% CI 0.655-0.889, P=0.001), with a sensitivity of 60.50%, a specificity of 85.00%, and the optimal critical value was 2.21%. Compared with the group with plasma CD24 positive rate>2.21%, the group with plasma CD24 positive rate<2.21% had a higher proportion of male (39.47%vs 65.00%, χ2=5.092, P=0.024), ISS stagingⅢ (41.67% vs 58.33%, χ2=6.175, P=0.046), β2 microglobulin (3.19 mg/L vs 4.14 mg/L, Z=-2.257, P=0.024), and BMPC [(8.672±1.827)% vs (19.530±3.188)%, t=-2.963, P=0.004] detected by MFC, and the differences were statistically significant. Conclusions:The low positive rate of plasma cell CD24 is closely related to the higher tumor burden and the worse disease status of MM patients. In addition, the positive expression rate of CD24 is at initial diagnosis can predict the efficacy achieved after induction therapy, and the lower positive rate of CD24 is, the worse the efficacy achieved after induction therapy. At the same time, MFC detection of CD24 is convenient and efficient in the evaluation and prediction of MM.

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.