Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objective To investigate the clinical efficacy of Chinese medicine sequential therapy combined with Clomiphene in the treatment of ovulatory disorder infertility(ODI),and to observe the effects of the combined therapy on the endometrial thickness,ovarian diameter,ovulation rate and pregnancy rate of the patients.Methods A total of 120 patients with ODI admitted to the Department of Obstetrics and Gynecology of the 7th People's Hospital of Zhengzhou from July 2021 to August 2023 were randomly divided into the control group and the observation group,with 60 patients in each group.The two groups were treated with Clomiphene,and additionally the observation group was treated with Chinese medicine sequential therapy of"nourishing yin and enriching blood,warming kidney to resolve phlegm and unblock collaterals,and tonifying kidney and strengthening spleen"in accordance with the menstrual cycle.Three menstrual cycles constituted a course of treatment.Before and after treatment,the changes in the traditional Chinese medicine(TCM)syndrome scores of the two groups were observed.After treatment for three menstrual cycles,the clinical efficacy,endometrial thickness,follicle diameter,ovulation rate,pregnancy rate,incidence of biphasic basal body temperature(BBT),and the incidence of adverse reactions after in the two groups were compared.Results(1)After three menstrual cycles of treatment,the total effective rate of the observation group was 96.67％(58/60)and that of the control group was 83.33％(50/60),and the comparison between the two groups showed that the efficacy of the observation group was significantly superior to that of the control group,the difference being statistically significant(x2=5.926,P＜0.05).(2)After three menstrual cycles of treatment,the TCM scores of patients in both groups were decreased significantly compared with those before treatment(P＜0.01),and the decrease of the scores in the observation group was significantly superior to that in the control group,with statistically significant differences(P＜0.01).(3)After three menstrual cycles of treatment,the follicle diameter of the observation group was longer than that of the control group,and the incidence of biphasic BBT[60.00％(36/60)],ovulation rate[63.33％(38/60)],and pregnancy rate[25.00％(15/60)]were higher than those of the control group,which were 31.67％(19/60),41.67％(25/60),and 10.00％(6/60),respectively.The differences of the above four indicators between the two groups were statistically significant(P＜0.05 or P＜0.01).However,the differences of endometrial thickness and the incidence of adverse reactions between the two groups were not statistically significant(P＞0.05).Conclusion Chinese medicine sequential therapy combined with Clomiphene exerts certain efficacy in treating patients with ODI,which can effectively relieve clinical symptoms,improve the BBT conditions,enhance the ovulation rate and pregnancy rate,with high safety.

Objective To analyze the relationship between fragmented QRS(fQRS)and microalbuminuria(MAU)and serum uric acid(SUA)in patients with type 2 diabetes mellitus(T2DM).Methods From October 2022 to June 2023,245 T2DM patients diagnosed by The Department of Endocrinology,Jinhua Hospital Affiliated to Zhejiang University School of Medicine were selected and divided into fQRS group(fQRS,n=111)and T2DM group(n=134)according to ECG results.The general data,biochemical indexes,left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd),interventricular septum(IVS),left ventricular posterior wall(LVPW),left ventricular ejection fraction(LVEF),left atrial diameter(LAd),peak value ratio of mitral orifice blood flow velocity in early and late diastole(E/A)and mitral orifice blood flow velocity in early diastole were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between fQRS wave and other indexes in T2DM patients,and Logistic regression analysis was used to analyze the influencing factors of fQRS.Results The prevalence rates of UACR,SUA,HbA1c and MAU in fQRS group were higher than in T2DM group(P＜0.05 or P＜0.01).LVEDd,LAd,E,E/e'and E/A>1.5 in QRS group were higher than in T2DM group(P＜0.05 or P＜0.01).Pearson correlation analysis showed that fQRS wave was positively correlated with smoking history,BMI,HbA1c,UACR,MAU,SUA,LVEDd,LAd,E/A and E/e'(P＜0.05).Logistic regression analysis showed that MAU was the influencing factor of fQRS wave in T2DM patients.Conclusions The fQRS in ECG in patients with T2DM is associated with MAU and SUA and may be an important evidence of myocardial fibrosis associated with subclinical cardiac diastolic dysfunction.

Objective:To solve international students' problems of learning difficulties and passive learning caused by language barriers in the process of biochemistry learning from the perspective of teachers in this specialty.Methods:Eighty international students were randomly divided into experimental group and control group. In the experimental group, the regional management mode was introduced in teaching, allowing students to speak mother tongues or English for group discussions on well-designed questions, and at the same time, classroom quizzes and stage tests were given, introducing formative evaluation to supervise students' learning and assess their learning performance. The control group received conventional teaching. The learning effects were assessed through a final exam and questionnaire survey. SPSS 25.0 was used to perform the Kruskal-Wallis H test and Nemenyi test. Results:Twenty-seven (75.00%) students believed that group discussion by region could deepen the discussion of questions; 27 (75.00%) no longer felt difficult, or even felt easy, to learn biochemistry; and nearly 90.00% of the students affirmed the formative evaluation mode, believing that it had positive effects on their learning attitude and behavior. In addition, the median exam score of the experimental group was 36.94% higher than that of the control class in the same year.Conclusions:Regional management combined with formative evaluation can promote international students' learning enthusiasm, improve their comprehensive achievement, and positively affect their learning behavior.

Objective:To explore the dynamic changes of inflammatory cytokines and T lymphocyte activation in the peripheral blood of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients during anti-retroviral therapy (ART).Methods:Two hundred and six HIV/AIDS patients with ART at clinic of the Department of Infectious Diseases in Second Xiangya Hospital, Central-South University between January 2017 and December 2019 were selected as HIV infection group. They were followed up regularly and the blood samples before treatment and at month 6, month 12, month 24 of treatment were collected. Meanwhile, 52 healthy cases were enrolled in the healthy control group and their blood samples were collected. Enzyme-linked immunosorbent assay was used to detect the plasma concentrations of interleukin (IL)-6, hypersensitive C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-α. Flow cytometry was used to detect the CD3 + CD4 + T lymphocytes count and the percentage of CD4 + CD38 + T lymphocytes and CD8 + CD38 + T lymphocytes in the peripheral blood mononuclear cells. Plasma HIV RNA viral load was determined using a quantitative real-time polymerase chain reaction technique. Statistical methods used paired t test and Pearson correlation analysis. Results:The concentrations of IL-6, hsCRP and TNF-α in HIV infection group were (13.42±2.35) pg/mL, (4 012.46±1 012.35) μg/L and (51.78±11.32) μg/L, respectively, which were higher than those in healthy control group ((6.14±0.78) pg/mL, (707.21±305.76) μg/L and (19.01±6.48) μg/L, respectively). The differences were all statistically significant ( t=12.56, 16.79 and 13.45, respectively, all P<0.001). They decreased gradually after initiation of ART in HIV infection group, and returned to normal levels at month 24 of ART. CD3 + CD4 + T cells count was (256.00±65.32)/μL and HIV RNA viral load was (4.467±4.244) lg copies/mL before ART in HIV infection group, which were negatively correlated ( r=-0.625, P=0.041). The percentages of CD8 + CD38 + T lymphocytes before treatment and at month 12 or month 24 of treatment in HIV infection group were higher than those in healthy control group. The differences were all statistically significant ( t=3.85, 6.84 and 2.57, respectively, all P<0.050). The percentage of CD8 + CD38 + T lymphocytes was positively correlated with HIV RNA viral load before ART ( r=0.768, P=0.026). The percentages of CD4 + CD38 + T lymphocytes before treatment and at month 12 or month 24 of treatment in the HIV infection group were lower than those in the healthy control group, and the differences were all statistically significant ( t=6.80, 1.10, and 2.11, respectively, all P<0.050). Conclusions:HIV infection could not only cause insufficiency in immune system, but also abnormal activation of immune system, which could get better gradually with ART.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

Objective To analyze the clinical diagnosis and treatment data of 20 children with hypophosphatemic rickets (HR) in order to improve the clinical diagnosis and treatment of HR.Methods The retrospective analysis of clinical data of 20 cases with HR who were hospitalized at Children's Hospital of Nanjing Medical University from May,2010 to April,2016 was performed to summarize the clinical characteristics.All patients were analyzed for the phosphate regulating gene with homologies to endopeptidase on the X chromosome(PHEX) gene by direct sequencing.If no mutations were detected,multiplex ligation-dependent probe amplification analysis was performed.Results All of the 20 cases with HR showed different degrees of growth retardation and typical X-ray rickets.After treatment,the clinical features were improved.Height standard deviation score (HSDS) was improved significantly with longer treatment time,and the difference was statistically significant(P =0.027).There was a correlation between the blood phosphorus fluctuation and secondary hyperparathyroidism(P ＜ 0.05).Nineteen cases had PHEX gene mutations.Truncating mutations was the most frequent mutation type,and 4 new mutations were found.Conclusions Clinical characteristics,laboratory test results and X-ray examination are important clinical index for the diagnosis of HR,and PHEX gene test can be used as an important auxiliary diagnostic tool.Early diagnosis and treatment can significantly improve the clinical manifestations of the patients.

Three weeks’ training, visiting and demonstrating classes in Michigan State University gave us an opportunity to understand the education system, the teaching characteristics and the “students centered”teaching principle of USA. Some reasonable teaching methods were applied in the class which may embody the student-oriented teaching aim and develop the students’ subjective initiative. The teaching effect showed that most students were fond of the teaching strategies and they also did good job in final tests.