Geminiviruses cause substantial crop yield losses worldwide. The replication initiator protein (Rep) encoded by geminiviruses is indispensable for geminiviral replication. The Rep protein encoded by beet severe curly top virus (BSCTV, genus Curtovirus, family Geminiviridae) induces VARIANT IN METHYLATION 5 (VIM5) expression in Arabidopsis leaves upon BSCTV infection. VIM5 functions as a ubiquitination-related E3 ligase to promote the proteasomal degradation of methyltransferases, resulting in reduction of methylation levels in the BSCTV C2-3 promoter. However, the specific domains of Rep responsible for VIM5 induction remain poorly characterized. Although Rep proteins from several geminiviruses act as viral suppressors of RNA silencing (VSRs), whether BSCTV Rep also possesses VSR activity remains to be illustrated. In this study, we employed a transient expression system in the 16c-GFP transgenic and the wild-type Nicotiana benthamiana plants to analyze the VSR and the VIM5-inducing activities of different truncated Rep proteins haboring distinct domains. We found that the N-terminal domain (amino acids 1-180) of Rep suppressed GFP silencing in 16c-GFP transgenic N. benthamiana leaves. The minimal N-terminal fragment (amino acids 1-104) induced VIM5 expression upon co-infiltration, while C-terminal truncations lacked VIM5-inducing activity. Our results indicate that the N-terminal domain of Rep encoded by BSCTV mediates the suppression of RNA silencing and induces VIM5 expression. Thus, our findings contribute to a better understanding of interactions between geminiviral Rep and plant hosts.
Geminiviridae/genetics* ; Nicotiana/metabolism* ; Arabidopsis/metabolism* ; RNA Interference ; Viral Proteins/metabolism* ; Arabidopsis Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Protein Domains ; Plant Diseases/virology* ; Methyltransferases/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; DNA Helicases/genetics*

ObjectiveTo compare the effect of toe-spread-out exercises (TSO) and modified TSO in females with hallux valgus. MethodsFrom September to December, 2023, a total of 45 females with hallux valgus were recruited in Capital University of Physical Education and Sports and randomly divided into blank control group (n = 15), TSO group (n = 15), and modified TSO group (n = 15). The blank control group received no intervention, the TSO group received routine TSO, and the modified TSO group received fibularis longus fascia release followed by TSO, for eight weeks. Changes in the hallux valgus angle (HVA) and the cross-sectional area (CSA) of the abductor hallucis muscle were measured before intervention, and four and eight weeks after intervention, respectively. ResultsOne case dropped out from the blank control group. The changes of HVA in the TSO and modified TSO groups were significantly greater than in the blank control group (F > 15.263, P < 0.05). After four weeks of intervention, the change of left HVA in the modified TSO group was significantly greater than in the TSO group (P < 0.05). The main effect of time was significant on the CSA of the abductor hallucis muscle (F > 13.245, P < 0.05). The main effect of group was significant on the left foot's CSA of the abductor hallucis (F = 3.798, P < 0.05). The interaction effect of time and group was also significant (F > 4.744, P < 0.05). The CSA of the abductor hallucis in both the TSO and modified TSO groups after four weeks and eight weeks of intervention was significantly greater than before intervention (P < 0.05). At eight weeks, the CSA of the right foot in the modified TSO group was significantly greater than in the blank control group (P < 0.05). ConclusionBoth TSO and modified TSO can improve HVA and the CSA of the abductor hallucis muscle in females with hallux valgus, and modified TSO is better.

ObjectiveTo compare the effect of three kinds of intrinsic foot muscle exercise on flatfoot. MethodsFrom September to November, 2022, 45 subjects with flatfoot from Capital University of Physical Education and Sports were randomly divided into short foot exercise (SFE) group (n = 15), toe-spread-out exercise (TSOE) group (n = 15) and short foot & toe-spread-out exercise (SF+TSOE) group (n = 15), who received SFE, TSOE and SF+TSOE, respectively, for eight weeks. The cross-sectional area of abductor hallucis muscle, navicular drop test (NDT) and Chippaux-Smirak index (CSI) were measured before treatment, four weeks after treatment and eight weeks after treatment. ResultsThree subjects dropped out in each group. The main effect of time was significant for left and right cross-sectional area of abductor hallucis muscle, NDT and CSI (F > 13.906, P < 0.001). The main effect of group was not significant for left and right cross-sectional area of abductor hallucis muscle, NDT and CSI (F < 1.934, P > 0.05). The interaction effect of group and time was significant for left and right NDT (F > 3.044，P < 0.05), and it was better in SF+TSOE group than in SFE group and TSOE group (P < 0.05). ConclusionSF and TSOE can improve the cross-sectional area of abductor hallucis muscle and foot morphology in subjects with flatfoot, and the combination of them may be more effective.

ObjectiveTo systematically review the effects of short-foot exercise on adult flatfoot. MethodsArticles related to short-foot exercise for flatfoot were searched from PubMed, Web of Science, Cochrane, Embase, Scopus, CNKI, Wanfang Data and CBM, from January, 2010 to December, 2022. The methodological quality was evaluated with the Physiotherapy Evidence Database (PEDro) scale, and the relevant data were extracted. ResultsTen randomized controlled trials were included, involved 335 individuals. The mean score of the PEDro scale was 7.1. Short-foot exercise improved the navicular drop, posture index score, balance and cross-sectional area of abductor hallucis muscle for patients with flatfoot, but plantar pressure. ConclusionShort-foot exercise can improve the foot structure, balance and adductor hallucis muscle in adult flatfoot, but plantar pressure.

OBJECTIVES: There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM. METHODS: The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0. RESULTS: Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%). CONCLUSIONS In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Humans ; Immunologic Factors/therapeutic use* ; Male ; Middle Aged ; Multiple Myeloma/therapy* ; Neoplasm Staging ; Pain ; Prognosis ; Proteasome Inhibitors/therapeutic use*

Objective To study the impact of brief intervention on HPV cognition of medical students in Xinjiang, and to provide a reference for the development of HPV related education in medical students. Methods Sudents from 20 classes of a medical university in Xinjiang were randomly selected. The first 10 classes were enrolled into group 1, which was a self-controlled study group evaluating the effect before and after intervention. The other 10 classes were included in group 2, in which students in each class were randomly divided into control group (filling in questionnaires before the intervention) and intervention group (filling in questionnaires after the intervention). Medical students were given a 10 minutes presentation on the intervention of HPV by trained personnel. Results (1) For HPV related knowledge, the difference in the awareness rates between the two groups before and after intervention was statistically significant (P < 0.001), and the awareness rate after intervention was higher than that before intervention. Before the intervention, the awareness rates of medical students in group 1 and group 2 were 18.67% and 17.71%, respectively, which increased to 66.75% and 52.85% after the intervention (P<0.01). (2) Regarding HPV-related attitudes and behavioral content, the differences in the response results of the two groups of students before and after the intervention were statistically significant (P<0.05), showing a more positive state after the intervention. Before the intervention, there were 86.19% and 88.02% of the students in group 1 and group 2 willing to publicize HPV-related knowledge to their relatives and friends, and the numbers increased to 94.12% and 94.82%, respectively, after the intervention (P < 0.05). Conclusion Both self-controlled and parallel-controlled studies demonstrated that brief interventions improved medical students' awareness of HPV.

Objective To evaluate the change of clinicopathological features and prognosis of papillary thyroid cancer over a 15-year period.Methods The clinicopathological features and outcomes of papillary thyroid cancer patients were analyzed in three groups according to the time of diagnosis:group Ⅰ (1997-2001),group Ⅱ (2002-2006),and group Ⅲ (2007-2011).Results As time advanced,the average age of papillary thyroid cancer patients increased,tumor stage,like size,extrathyroid invasion and lymph node metastasis decreased dramatically (P ＜ 0.01).The percentage of multifocality and bilaterality increased.The long-term follow up data (median follow up time was 6.6 years),indicated that the 15-year over all survival was 97.8％ and the 15-year disease-free survival was 90.2％.Tumor ≥3 cm,bilaterality,extrathyroid invasion,lymph node metastasis and AJCC stage were correlated with tumor recurrence.By multivariate COX-regression analysis only lymph node metastasis and bilaterality were independent risk factors.Conclusion The clinicopathological features of papillary thyroid cancer changed over 15 years,with the percentage of early-staged patients increased.Lymph node metastasis and bilaterality are two risk factors for tumor recurrence.

Objective:To compare the clinical effect of anterior and posterior resection,bone grafting and internal fixation on the spinal tuberculosis.Methods:82 cases of patients with spinal tuberculosis in our hospital from February 2014 to August 2015 were selected and randomly divided into the control group and the observation group with 41 cases in each group.Both groups received conventional anti tuberculosis treament and underwent debridement bone graft and internal fixation treatment,the control group underwent anterior internal fixation,while the observation group underwent posterior internal fixation.The operation time,intraoperative blood loss,low back pain relief time,ambulation time and hospitalization time were compared between two groups.All patients were followed up for 6 months,the Frankel grade and serum Thl7 cell related factors levels were compared between two groups before and after operation.Results:The low back pain relief time,ambulation time and hospitalization time of observation group were significantly shorter than those of the control group(P＜0.01).After operation,the Frankel classification grade A and B ratio of observation group were significantly higher than those of the control group (P＜0.05),the serum IL-10,IL-17,IL-23 and TGF-beta 1 levels were significantly lower than those of the control group (P＜0.01).Conclusion:Anterior resection combined with posterior bone graft inFixation could effectively promote the rehabilitation of spinal tuberculosis,reduce the severity of spinal injury,relieve the inflammatory response and promote the recovery of immune function.

Complement activation-related pseudo-allergic reactions (CARPA) may represent 77% of all immune-mediated immediate hypersensitivity reactions. Because of the universality of the CARPA response and correlation between it and drug properties, complement activity tests are recommended as one of the tests for immunotoxicity and bioequivalence of drugs. However, in-vivo tests of complement activation are complicated, and the immunological differences between different individuals and between human and animal, making it very necessary to establish a standard and sample evaluation model for testing the effects of drugs on complement activity. In this study, the standard reaction serum was prepared by pooling sera collected from 40 healthy blood donors; a standard positive control was prepared by incubation with a heat-agglutinated IgG and zymosan A; SC5b-9, C5a, C4d and Bb were chosen as the test targets and evaluation criteria of the results was defined, all of these constituted the in-vitro model. By using this in-vitro model, the immunological toxicity of the different prescription of antifungal drug amphotericin B, and voriconazole for injection, and the bioequivalence of amphotericin B liposome formulations were studied.

Objective:To prepare a virus-like particle (VLP),containing Hepatitis B virus core antigen (HBcAg) and N-terminal peptides of the L2 protein of human papilloma virus (HPV),and investigate the immunogenicity of the VLP in mice and the protection against different strains of HPV .Methods:A fusion gene was synthesized to insert a DNA fragment ,coding for the N-terminal epitopes of the L2 protein of HPV16,into the HBcAg coding sequence;HBc-L2 fusion protein was highly expressed in E.coli using the pET9a and BL21(DE3) expression system;the purified fusion protein was used to immunize BALB/c mice and antibody titers against the L2 epitopes in mouse sera were determined by indirect ELISA;the levels of neutralizing antibodies against both HPV 16 and 18 were also analyzed.Results:HBc-L2 fusion protein was expressed in E.coli and purified,with the purity >80%,by ammonium sulfate pre-cipitation and CL-4B gel filtration;analysis of the purified fusion protein ,using size exclusion chromatography with multi-angle laser light scattering detection ( SEC-MALS) and electron microscope ,revealed that HBc-L2 was assembled into a stable VLP structure auto-matically following its expression;immunization of BALB/c mice with the purified VLPs resulted in high antibody titers in mouse sera against the L2 epitopes;furthermore,it was demonstrated that the sera from the immunized mice had neutralization activities against both HPV16 and HPV18.Conclusion:The immunogenicity of the L2 epitopes was highly enhanced by the construction of HBc-L2 fusion protein and the formation of the VLP structure;the fusion protein was also capable of inducing protections against different serotypes of HPV,therefore,it could be a potential HPV vaccine with a broad coverage and low production cost .