The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Purpose::Shaping and assembling contemporary external fixators rapidly for the severe mandibular fractures remains a challenge, especially in emergency circumstance. We designed a novel external fixator that incorporates universal joints to provide the stabilization for mandibular comminuted fractures. This study aims to confirm the efficacy of this novel external fixator through biomechanical tests in vitro and animal experiments. Methods::In vitro biomechanical tests were conducted using 6 fresh canine with mandibular defect to simulate critical comminuted fractures. Three mandibles were stabilized by the novel external fixator and other mandibles were fixed by 2.5 mm reconstruction plates. All fixed mandibles were subjected to loads of 350 N on the anterior regions of teeth and 550 N on the first molar of the unaffected side. The stability was evaluated based on the maximum displacement and the slope of the load-displacement curve. In animal experiments, 9 beagles with comminuted mandibular fractures were divided into 3 groups, which were treated with the novel external fixation, reconstruction plate, and dental arch bar, respectively. The general observation, the changes in animals’ weight, and the surgical duration were recorded and compared among 3 groups. The CT scans were performed at various intervals of 0 day (immediately after the surgery), 3 days, 7 days, 14 days, 21 days, and 28 days to analyze the displacement of feature points on the canine mandible and situation of fracture healing at 28 days. The statistical significance was assessed by the two-way analysis of variance test followed by the Bonferroni test, enabling multiple comparisons for all tests using GraphPad Prism10.1.0 (GraphPad Inc, USA). Results::The outcomes of the biomechanical tests indicated that no statistically significant differences were found in terms of the maximum displacement ( p = 0.496, 0.079) and the slope of load displacement curves ( p = 0.374, 0.349) under 2 load modes between the external and internal fixation groups. The animal experiment data showed that there were minor displacements of feature points between the external and internal fixation groups without statistic difference, while the arch bar group demonstrated inferior stability. The CT analysis revealed that the best fracture healing happened in the internal fixation group, followed by the external fixation and arch baring at 28 days after fixation. The external fixation group had the shortest fixation duration (25.67 ± 3.79) min compared to internal fixation ((70.67 ± 4.51) min, p < 0.001) and arch baring ((42.00 ± 3.00) min, p = 0.046). Conclusion::The conclusion of this study highlighted the efficacy and reliability of this novel external fixator in managing mandibular fractures rapidly, offering a viable option for the initial stabilization of comminuted mandibular fractures in the setting of emergency rescue.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To construct the performance evaluation index system of public hospitals,and provide reference for promoting the high-quality development of public hospitals.Methods Delphi method and analytic hierarchy process were used to determine the performance evaluation index system of public hospitals based on performance prism model.Results It established a public hospital performance evaluation system including 5 first-level indicators,16 second-level indicators and 40 third-level indicators of government,staff,patients,suppliers and regulatory agencies.The weights of the five first-level indicators are 0.254 8,0.476 8,0.154 4,0.073 4 and 0.040 6,respectively.Among the 16 second-level indicators,salary,quality and safety,practice environment,medical quality and operation efficiency rank the top 5.The combined weights were 0.268 5,0.174 3,0.165 4,0.080 9 and 0.060 6,respectively.Among the 40 tertiary indicators,the satisfaction of medical staff,the quality control index of single disease,organizational support,the intensity of antibacterial drug use and the case mortality of the low-risk group were investigated.The combined weights were 0.212 0,0.110 0,0.107 0,0.064 3 and 0.0624,respectively.Conclusion The performance evaluation index system of public hospitals based on the performance prism model established is helpful to guide hospitals to think about hospital strategic reform,process optimization and capacity improvement from the multi-dimensional perspective of internal and external stakeholders,so as to improve development performance and promote social harmonious development,and to improve performance,promote high-quality development.

Objective To construct the performance evaluation index system of public hospitals,and provide reference for promoting the high-quality development of public hospitals.Methods Delphi method and analytic hierarchy process were used to determine the performance evaluation index system of public hospitals based on performance prism model.Results It established a public hospital performance evaluation system including 5 first-level indicators,16 second-level indicators and 40 third-level indicators of government,staff,patients,suppliers and regulatory agencies.The weights of the five first-level indicators are 0.254 8,0.476 8,0.154 4,0.073 4 and 0.040 6,respectively.Among the 16 second-level indicators,salary,quality and safety,practice environment,medical quality and operation efficiency rank the top 5.The combined weights were 0.268 5,0.174 3,0.165 4,0.080 9 and 0.060 6,respectively.Among the 40 tertiary indicators,the satisfaction of medical staff,the quality control index of single disease,organizational support,the intensity of antibacterial drug use and the case mortality of the low-risk group were investigated.The combined weights were 0.212 0,0.110 0,0.107 0,0.064 3 and 0.0624,respectively.Conclusion The performance evaluation index system of public hospitals based on the performance prism model established is helpful to guide hospitals to think about hospital strategic reform,process optimization and capacity improvement from the multi-dimensional perspective of internal and external stakeholders,so as to improve development performance and promote social harmonious development,and to improve performance,promote high-quality development.

Objective To construct the performance evaluation index system of public hospitals,and provide reference for promoting the high-quality development of public hospitals.Methods Delphi method and analytic hierarchy process were used to determine the performance evaluation index system of public hospitals based on performance prism model.Results It established a public hospital performance evaluation system including 5 first-level indicators,16 second-level indicators and 40 third-level indicators of government,staff,patients,suppliers and regulatory agencies.The weights of the five first-level indicators are 0.254 8,0.476 8,0.154 4,0.073 4 and 0.040 6,respectively.Among the 16 second-level indicators,salary,quality and safety,practice environment,medical quality and operation efficiency rank the top 5.The combined weights were 0.268 5,0.174 3,0.165 4,0.080 9 and 0.060 6,respectively.Among the 40 tertiary indicators,the satisfaction of medical staff,the quality control index of single disease,organizational support,the intensity of antibacterial drug use and the case mortality of the low-risk group were investigated.The combined weights were 0.212 0,0.110 0,0.107 0,0.064 3 and 0.0624,respectively.Conclusion The performance evaluation index system of public hospitals based on the performance prism model established is helpful to guide hospitals to think about hospital strategic reform,process optimization and capacity improvement from the multi-dimensional perspective of internal and external stakeholders,so as to improve development performance and promote social harmonious development,and to improve performance,promote high-quality development.

Objective To construct the performance evaluation index system of public hospitals,and provide reference for promoting the high-quality development of public hospitals.Methods Delphi method and analytic hierarchy process were used to determine the performance evaluation index system of public hospitals based on performance prism model.Results It established a public hospital performance evaluation system including 5 first-level indicators,16 second-level indicators and 40 third-level indicators of government,staff,patients,suppliers and regulatory agencies.The weights of the five first-level indicators are 0.254 8,0.476 8,0.154 4,0.073 4 and 0.040 6,respectively.Among the 16 second-level indicators,salary,quality and safety,practice environment,medical quality and operation efficiency rank the top 5.The combined weights were 0.268 5,0.174 3,0.165 4,0.080 9 and 0.060 6,respectively.Among the 40 tertiary indicators,the satisfaction of medical staff,the quality control index of single disease,organizational support,the intensity of antibacterial drug use and the case mortality of the low-risk group were investigated.The combined weights were 0.212 0,0.110 0,0.107 0,0.064 3 and 0.0624,respectively.Conclusion The performance evaluation index system of public hospitals based on the performance prism model established is helpful to guide hospitals to think about hospital strategic reform,process optimization and capacity improvement from the multi-dimensional perspective of internal and external stakeholders,so as to improve development performance and promote social harmonious development,and to improve performance,promote high-quality development.

Objective To construct the performance evaluation index system of public hospitals,and provide reference for promoting the high-quality development of public hospitals.Methods Delphi method and analytic hierarchy process were used to determine the performance evaluation index system of public hospitals based on performance prism model.Results It established a public hospital performance evaluation system including 5 first-level indicators,16 second-level indicators and 40 third-level indicators of government,staff,patients,suppliers and regulatory agencies.The weights of the five first-level indicators are 0.254 8,0.476 8,0.154 4,0.073 4 and 0.040 6,respectively.Among the 16 second-level indicators,salary,quality and safety,practice environment,medical quality and operation efficiency rank the top 5.The combined weights were 0.268 5,0.174 3,0.165 4,0.080 9 and 0.060 6,respectively.Among the 40 tertiary indicators,the satisfaction of medical staff,the quality control index of single disease,organizational support,the intensity of antibacterial drug use and the case mortality of the low-risk group were investigated.The combined weights were 0.212 0,0.110 0,0.107 0,0.064 3 and 0.0624,respectively.Conclusion The performance evaluation index system of public hospitals based on the performance prism model established is helpful to guide hospitals to think about hospital strategic reform,process optimization and capacity improvement from the multi-dimensional perspective of internal and external stakeholders,so as to improve development performance and promote social harmonious development,and to improve performance,promote high-quality development.