Evaluating the safety and efficacy of cryopreserved ovarian tissue transplantation in leukemia patients with different bone marrow remission status using xenotransplantation.

Background: Leukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC). Objective: To explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation. Method: Cryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient's MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice. Results: Follicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (p<0.01) was noted, the uterine volume was notably larger, estradiol (E2) levels were significantly higher (p<0.01), and follicle-stimulating hormone (FSH) levels were significantly lower (p<0.001) in the other two groups. Mice in the MRD-positive group showed a significantly higher incidence of death (p<0.001) and emaciation (p<0.01), compared to the MRD-negative group. Histological observation revealed the presence of malignant cells in the grafts, livers, and spleens of 3 mice in the MRD-positive group. No abnormalities were observed in the mice from the MRD-negative group in both macroscopic and histological observations except one mouse was sacrificed for ascites unrelated to leukemia relapse. Conclusion: For leukemia patients having ovarian tissue preserved in the first and only centralized human ovarian tissue cryobank in China, immunodeficient mice xenotransplantation can be a method to evaluate the safety and efficacy of OTT; the risk of malignant cell reimplantation due to OTT is higher in leukemia patients with MRD-positive status than those with MRD-negative status before OTC.

A label-free aptasensing method for detecting SARS-CoV-2 virus antigen by using dumbbell probe-mediated circle-to-circle amplification.

Controlling the spread of pathogen requires an efficient and accurate diagnosis. Compared with nucleic acid and antibody detection, antigen assays are more convenient to meet clinical diagnostic needs. However, antigen detection is often difficult to achieve high sensitivity in a limited time. In this work, a novel aptasensing method was designed for the purpose of SARS-CoV-2 antigen detection, using a dumbbell padlock probe-mediated circle-to-circle amplification (C2CA) approach. A sandwich complex of antibody-antigen-aptamer is first formed on the magnetic beads. Afterwards, the signal is amplified by a C2CA reaction involving two tandem rolling circle amplifications. Without special instruments or nanomaterials, a detection limit of 575 fg/mL for S1 protein can be achieved in less than 2 h. In the case of the spike pseudovirus SARS-CoV-2 in artificial saliva, the detection limit is 272 TU/µL, which is much lower than average viral load in patients. Therefore, our method provides a timely, efficient and accurate approach for the clinical diagnosis of SARS-CoV-2. It also opens up the application of C2CA in aptamer sensing and antigen detection.

Risk estimation for postoperative nausea and vomiting: development and validation of a nomogram based on point-of-care gastric ultrasound.

BACKGROUND: We aimed to develop a nomogram that can be combined with point-of-care gastric ultrasound and utilised to predict postoperative nausea and vomiting (PONV) in adult patients after emergency surgery. METHODS: Imaging and clinical data of 236 adult patients undergoing emergency surgery in a university hospital between April 2022 and February 2023 were prospectively collected. Patients were divided into a training cohort (n = 177) and a verification cohort (n = 59) in a ratio of 3:1, according to a random number table. After univariate analysis and multivariate logistic regression analysis of the training cohort, independent risk factors for PONV were screened to develop the nomogram model. The receiver operating characteristic curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the prediction efficiency, accuracy, and clinical practicability of the model. RESULTS: Univariate analysis and multivariate logistic regression analysis showed that female sex, history of PONV, history of migraine and gastric cross-sectional area were independent risk factors for PONV. These four independent risk factors were utilised to construct the nomogram model, which achieved significant concordance indices of 0.832 (95% confidence interval [CI], 0.771-0.893) and 0.827 (95% CI, 0.722-0.932) for predicting PONV in the training and validation cohorts, respectively. The nomogram also had well-fitted calibration curves. DCA and CIC indicated that the nomogram had great clinical practicability. CONCLUSIONS: This study demonstrated the prediction efficacy, differentiation, and clinical practicability of a nomogram for predicting PONV. This nomogram may serve as an intuitive and visual guide for rapid risk assessment in patients with PONV before emergency surgery.

Ovarian tissue cryopreservation in the pediatric with rare diseases- experience from China's first and the largest ovarian tissue cryobank.

Background: There is limited information about the efficacy of ovarian tissue cryopreservation (OTC) in children. In the present study, we report eight patients with rare diseases who underwent OTC in China's first and largest ovarian tissue cryobank. Procedure: Data from girls with rare diseases who underwent OTC between September 2020 and November 2022 were retrospectively analyzed. We also compared the number of cryopreserved cortex pieces, follicle number, and AMH in those with rare diseases and age-matched children with non-rare diseases who also underwent OTC in our cryobank. Results: The median age of the children was 5.88 ± 3.52 (range 2-13) years old. Unilateral oophorectomy was undertaken via laparoscopy in all of the children. The diseases in the 8 patients were: 4 mucopolysaccharidoses (MPS I two cases, IVA two cases), 1 Diamond-Blackfan anemia (DBA), 1 Fanconi anemia (FA), 1 hyperimmunoglobulin E syndrome (HIES), 1 Niemann-Pick disease. The number of cryopreserved cortex pieces was 17.13 ± 6.36, and the follicle count per 2 mm biopsy was 447.38 ± 524.35. No significant difference in age, the count of cryopreserved cortex pieces, follicle number per 2 mm biopsy, and AMH level was seen between the 20 children with non-rare diseases and those with rare diseases. Conclusions: The reports help practitioners counsel girls with rare diseases about fertility preservation. The demand for OTC in pediatrics will likely grow as a standard of care.

Differential lncRNA/mRNA expression profiling and ceRNA network analyses in amniotic fluid from foetuses with ventricular septal defects.

Background: Long noncoding RNAs (lncRNAs) have been shown to be involved in the regulation of numerous biological processes in embryonic development. We aimed to explore lncRNA expression profiles in ventricular septal defects (VSDs) and reveal their potential roles in heart development. Methods: Microarray analyses were performed to screen differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) in the amniotic fluid between the VSD group and the control group. Bioinformatics analyses were further used to identify the functional enrichment and signaling pathways of important mRNAs. Then, a coding-noncoding gene coexpression (CNC) network and competitive endogenous RNAs (ceRNA) network were drawn. Finally, qRT‒PCR was performed to verify several hub lncRNAs and mRNAs in the network. Results: A total of 710 DE-lncRNAs and 397 DE-mRNAs were identified in the VSD group. GO and KEGG analyses revealed that the DE-mRNAs were enriched in cardiac development-related biological processes and pathways, including cell proliferation, cell apoptosis, and the Sonic Hedgehog signaling pathway. Four VSD related mRNAs was used to construct the CNC network, which included 149 pairs of coexpressing lncRNAs and mRNAs. In addition, a ceRNA network, including 15 lncRNAs, 194 miRNAs, and four mRNAs, was constructed to reveal the potential regulatory relationship between lncRNAs and protein-coding genes. Finally, seven RNAs in the ceRNA network were validated, including IDS, NR2F2, GPC3, LINC00598, GATA3-AS1, PWRN1, and LINC01551. Conclusion: Our study identified some lncRNAs and mRNAs may be potential biomarkers and therapeutic targets for foetuses with VSD, and described the lncRNA-associated ceRNA network in the progression of VSD.

Efficacy and Safety of Ultrasound-Guided Percutaneous Ablation for Adrenal Metastases: A Meta-Analysis.

OBJECTIVES: To assess the efficacy and safety of ultrasound-guided percutaneous ablation (US-PA) for adrenal metastases (AMs) using a meta-analysis. METHODS: A systematic search of PubMed, Cochrane, Web of Science, and Embase electronic databases was performed to identify studies on US-PA for AM. Seven studies published between January 2000 and August 2022 were analyzed, which resulted in a sample size of 140 patients. Both random effects and common effects meta-analysis models were used to analyze the following efficacy and safety outcomes: the first and secondary technical success rate, 1-year overall survival rates, 1-year local tumor control rate, incidence rate of intraoperative hypertensive crises, and major complications. The subgroup analysis was performed to explore the origin of heterogeneity. RESULTS: Among 140 patients from 7 studies included in this meta-analysis: 51 (36.43%) underwent radiofrequency ablation (RFA), and 89 (63.57%) underwent microwave ablation (MWA). Pooled data analysis revealed that the first and secondary technical success rates were 85% (95% confidence interval [CI], 73-96) and 99% (95% CI, 96-100), the 1-year overall survival rate was 83% (95% CI, 71-93), the 1-year local tumor control rate was 83% (95% CI, 75-90), and the incidence rate of intraoperative hypertensive crises was 14% (95% CI, 8-20). The overall rate of major complications was 3.6%. In the subgroup analysis, lower heterogeneity was indicated to be associated with mean tumor size and ablation type. CONCLUSIONS: This meta-analysis showed that US-PA can be both effective and safe for AM in terms of overall survival, technical success rate, and local control for AM.

An ultrasensitive fluorescence aptasensor for SARS-CoV-2 antigen based on hyperbranched rolling circle amplification.

Sensitive and accurate diagnosis of SARS-CoV-2 infection at early stages can help to attenuate the effects of the COVID-19. Compared to RNA and antibodies detection, direct detection of viral antigens could reflect infectivity more appropriately. However, it is still a great challenge to construct a convenient, accurate and sensitive biosensor with a suitable molecular recognition element for SARS-CoV-2 antigens. Herein, we report a HRCA-based aptasensor for simple, ultrasensitive and quantitative detection of SARS-CoV-2 S1 protein and pseudovirus. The aptamer sequence used here is selected from several published aptamers by enzyme-linked oligonucleotide assay and molecular docking simulation. The sensor forms an antibody-target-aptamer sandwich complex on the surface of microplates and elicits HRCA for fluorescent detection. Without complicated operations or special instruments and reagents, the aptasensor can detect S1 protein with a LOD of 89.7 fg/mL in the linear range of 100 fg/mL to 1 µg/mL. And it can also detect SARS-CoV-2 spike pseudovirus in artificial saliva with a LOD of 51 TU/µL. Therefore, this simple and ultrasensitive aptasensor has the potential to detect SARS-CoV-2 infection at early stages. It may improve the timeliness and accuracy of SARS-CoV-2 diagnosis and demonstrate a strategy to conduct aptasensors for other targets.

Shear Wave Elastography for Detecting Calf Muscle Stiffness: An Effective Tool for Assessing Sarcopenia.

OBJECTIVES: To explore the feasibility of shear wave elastography for evaluating sarcopenia. METHODS: The shear wave velocities (SWV) of the tibialis anterior, medial gastrocnemius, and soleus were measured in 130 subjects in the Second Affiliated Hospital of Fujian Medical University from January 2021 to June 2022. Consistency was evaluated in 20 cases using the intraclass correlation coefficient. According to the 2019 Asian Working Group for Sarcopenia（AWGS） diagnostic criteria, the patients were divided into a healthy and a sarcopenia group. The differences in SWV between the two groups were compared, and their correlation between calf muscles and muscle mass, grip strength, and pace were analyzed. The diagnostic cutoff value of calf muscle SWV for sarcopenia was obtained using receiver operating characteristic (ROC) curves, and the diagnostic efficacy of different ROC curves was compared. RESULTS: The SWV inter-group and intra-group correlation coefficients of the three lower limbs muscles were all greater than 0.85. Moreover, the corresponding SWV in the sarcopenia group were significantly smaller than those in the healthy control group (P < .05). Further, SWV were positively correlated with the appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed. Finally, the SWV of the anterior tibialis and medial gastrocnemius muscles were 3.02 and 2.26 m/s, respectively, and their diagnostic efficacy for sarcopenia did not differ significantly (Z = 0.190, P = .8497). CONCLUSION: SWE can be used to detect the hardness of the anterior tibialis and medial gastrocnemius, calculate their muscle mass as an effective tool to evaluate sarcopenia.

Modeling for extracavity-pumped terahertz parametric oscillators.

This paper presents a modeling method for extracavity-pumped terahertz parametric oscillators (TPO) based on stimulated polariton scattering, in which the pumping beam is from a different laser, and the Stokes beam oscillates in its cavity. After suitable approximations and assumptions, the average THz wave amplitude in the nonlinear crystal is expressed as a function of the fundamental and Stokes wave amplitudes. Then the rate equation for the Stokes wave is obtained based on the Stokes wave increment within a cavity roundtrip timescale. After solving the Stokes wave rate equation, the Stokes wave temporal evolution is considered as a known parameter, and the properties of the residual fundamental and terahertz waves are obtained by numerically solving the coupled wave equations. This modeling method is applied to an extracavity-pumped TPO based on MgO:LiNbO3 crystal. The simulation results are basically consistent with the experimental results. The main reasons causing the deviations of the simulation results from the experimental results are analyzed. To the best of our knowledge, this is the first time to perform the modeling for extracavity-pumped Q-switched TPOs.

Genomic Characterization of ESBL/AmpC-Producing Escherichia coli in Stray Dogs Sheltered in Yangzhou, China.

Purpose: Limited data are available on the prevalence and antimicrobial resistance of extended spectrum ß-lactamase- (ESBL) and AmpC ß-lactamase-producing Escherichia coli in stray dogs. We aimed to investigate the genomic characteristics of ESBL/AmpC-producing E. coli isolated from stray dogs sheltered in Yangzhou, China. Methods: We collected 156 samples including 115 fecal swabs, 35 kennel floor swabs, two breeder hand and shoe sole swabs, and four feed samples. The isolates were tested for resistance by antimicrobial susceptibility testing and further analyzed for cefotaxime-resistant E. coli isolates by whole genome sequencing. Results: We identified 80 cefotaxime-resistant E. coli isolates (51.3%), 59 isolates (73.8%) from feces and 21 (26.2%) from the environment. Whole-genome sequencing analysis showed that bla CTX-M-15 (n=30) and bla CTX-M-55 (n=29) were the most prevalent genotypes. Two isolates only carried the AmpC ß-lactamase gene bla CMY-2; one isolate had a combination of AmpC ß-lactamase gene bla DHA-1 and ESBL ß-lactamase gene bla CTX-M-14. Other important resistance genes such as bla OXA-10, bla TEM-1B, bla TEM-135, bla TEM-106, tet(A), qnrS1, qnrB4, and oqxAB were also detected. The serotype combination was highly abundant, with O10:H25 predominating (n=12). Most cefotaxime-resistant E. coli isolates belonged to phylogroup A (62.5%, n=50), followed by phylogroup B1 (26.3%, n=21). Thirty different sequence types (STs) and 27 distinct plasmid replicons were identified, among which ST2325 (n=12) and IncFII (n=38) was the most frequent ST and plasmid, respectively. ESBL/AmpC-producing isolates were divided into four major clades; clade IV was the primary lineage containing 37 isolates from feces and 13 from the environment. Three high-risk E. coli clone ST23 strains and one ST10 strain belonged to clades III and IV, respectively. Conclusion: Our study provides a comprehensive overview of resistance profiles and genomic characteristics in ESBL/AmpC-producing E. coli and highlights the possible role of stray dogs as an antibiotic resistance gene reservoir.

Sintering and Mechanical Properties of (SiC + TiCx)p/Fe Composites Synthesized from Ti3AlC2, SiC, and Fe Powders.

Ceramic-particle-reinforced iron matrix composites (CPR-IMCs) have been used in many fields due to their excellent performance. In this study, using the fast resistance-sintering technology developed by our team, iron matrix composites (IMCs) reinforced by both SiC and TiCx particles were fabricated via the addition of SiC and Ti3AlC2 particles, and the resulting relative densities of the sintering products were up to 98%. The XRD and EDS analyses confirmed the in situ formation of the TiCx from the decomposition of Ti3AlC2 during sintering. A significant hybrid reinforcing effect was discovered in the (SiC + TiCx)p/Fe composites, where the experimental strength and hardness of the (SiC + TiCx)p/Fe composites were higher than the composites of monolithic SiCp/Fe and (TiCx)p/Fe. While, under the condition of constant particle content, the elongation of the samples reinforced using TiCx was the best, those reinforced by SiC was the lowest, and those reinforced by (SiC + TiCx) fell in between, which means the plastic response of (SiC + TiCx)p/Fe composites obeyed the rule of mixture. The successful preparation of IMCs based on the hybrid reinforcement mechanism provides an idea for the optimization of IMCs.

Establishment and verification of an osteoporosis risk model in patients with rheumatoid arthritis: a valuable new model.

To establish a model for osteoporosis risk in patients with rheumatoid arthritis and validate the model. A newly generated predictive model has been suggested to have good differentiation, calibration, and clinical validity and may be a useful clinical model for predicting osteoporosis in patients with rheumatoid arthritis. PURPOSE: To establish a prediction model for osteoporosis risk in patients with rheumatoid arthritis and validate the model internally and externally. METHODS: A total of 270 patients with rheumatoid arthritis who underwent bone mineral density measurement at our hospital from June 2019 to June 2020 were enrolled in the study. The patients were divided into two groups according to their entry time: a training set containing the first 2/3 of the patients (n = 180) and a validation set containing the remaining 1/3 of the patients (n = 90). Binary logistic regression analysis was used to establish the regression models, and the concordance index (C-index), calibration plot, and decision curve analysis were used to evaluate the prediction model. RESULTS: Five variables, including age (X1), course of disease (X2), the disease activity score using 28 joint counts (DAS28) (X4), anti-cyclic citrullinated peptide antibody (CCP) (X7), and 7-joint ultrasonic bone erosion (X14), were selected to enter the model. The prediction model is Logit Y = - 12.647 + 0.133X1 + 0.011X2 + 0.754X4 + 0.001X7 + 0.605X14. The model had good differentiation; the C-index in the internal verification was 0.947 (95% CI is 0.932-0.977) and the C-index in the external verification was 0.946 (95% CI is 0.940-0.994). The calibration plot of the model showed excellent consistency between the prediction probability and actual probability. When > 0.483 was taken as the cutoff value for the diagnosis of osteoporosis, the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and Jordan index of the model were 90.24%, 87.76%, 7.37, 0.11, and 78.00%, respectively. CONCLUSION: A newly generated predictive model has been suggested to have good differentiation, calibration, and clinical validity and may be a useful clinical model for predicting osteoporosis in patients with rheumatoid arthritis.

Screening aptamers for serine ß-lactamase-expressing bacteria with Precision-SELEX.

Klebsiella pneumoniae carbapenemase 2 (KPC-2) is a serine ß-lactamase that can hydrolyze almost all ß-lactam antibiotics. The drug resistant problem of bacteria expressing carbapenemases is currently a global problem, therefore, rapid and specific detection of pathogenic bacteria is urgent. In order to obtain an aptamer that can specifically recognize bacteria expressing KPC-2, we have established a method called Precision-SELEX. Precision-SELEX combined protein SELEX and bacterium SELEX. In this method, KPC-2 was used as a target protein, and Escherichia coli expressing KPC-2 (KPC-2 E. coli) was used as a target bacterium. After precision-SELEX, the same aptamer named XK-10 that can recognize KPC-2 and KPC-2 E. coli was obtained while the screening process could be shortened to 4 rounds. Dissociation equilibrium constants were calculated as 0.81 nM by SPR. In addition, XK-10 could specifically bind to KPC-2 E. coli, which was confirmed through flow cytometry and molecular Docking Simulations. The high-content imaging method could detect KPC-2 E. coli. In all, the Precision-SELEX provides an accurate and efficient method to screening aptamers for bacteria.

The discovery of lactoferrin dual aptamers through surface plasmon resonance imaging combined with a bioinformation analysis.

An analytical method for screening aptamers for different recognition sites in lactoferrin (Lac) molecules has been developed based on Surface Plasmon Resonance imaging (SPRi), combined with the cluster classification calculation of a quasi-aptamer library strategy and molecular docking simulation analysis. Using the software simulation, a homology analysis was performed on the selected quasi-aptamer sequences, which could be divided into 8 different families. Based on the principle of biomolecular recognition, a label-free, high-throughput dual immune site screening method was established, in which the nucleic acid aptamers of recognizing ability for lactoferrin molecules were fixed onto the surface of the SPRi sensor chip and could bind to the lactoferrin molecules. Then, the aptamer candidates to be paired were introduced, and the recognition event of the second immune site was judged by observing the binding signal of SPRi. The paired SPRi signal was generated only when the site identified by the second nucleic acid molecule was different from the first immune site. Based on this principle, a pair of Lac nucleic acid aptamers (Lac-8 and Lac-25) was finally screened and confirmed using computerized simulation, and has been employed to assay Lac in milk by ELONA (Enzyme-Linked Oligonucleotide Assay).

Modeling of intracavity-pumped Q-switched terahertz parametric oscillators based on stimulated polariton scattering.

In this paper, the rate equations describing the operation of intracavity-pumped Q-switched terahertz parametric oscillators based on stimulated polariton scattering are given for the first time. The rate equations are obtained under the plane-wave approximation, the oscillating fundamental and Stokes waves are supposed to be round uniform beam spots. Considering the fact that the terahertz wave nearly traverses the pump and Stokes beams and using the coupled wave equations, the terahertz wave intensity is expressed as the function of the fundamental and Stokes intensities. Thus, the rate equations describing the evolution processes of the fundamental and Stokes waves are obtained in the first step. The THz wave properties are then obtained. Several curves based on the rate equations are generated to illustrate the effects of the nonlinear coefficient, the THz wave absorption coefficient, and pulse repetition rate on the THz laser characteristics. Taking the intracavity-pumped Mg:LiNbO3 TPO as an example, the THz frequency tuning characteristic and the dependences of the fundamental, Stokes, and THz wave powers on the incident diode pump power are calculated. The theoretical results are in agreement with the experimental results on the whole.

ALDH2 Gene: Its Effects on the Neuropsychological Functions in Patients with Opioid Use Disorder Undergoing Methadone Maintenance Treatment.

OBJECTIVE: Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2(ALDH2) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT). METHODS: OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors' Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R. RESULTS: We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2＋*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p= 0.03), significantly lower hit reaction time T-scores (p= 0.04), and significantly lower WMS-R visual memory index scores (p= 0.03) than did patients with the ALDH2 1*/*1 (ALDH2 active) genotype. CONCLUSION: OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.

Robust digital holography design with monitoring setup and reference tilt error elimination.

A robust digital holography recording design is presented to complete the work of switching between in-line and off-axis recording methods. We precisely supervise the off-axis angle in off-axis holography, so that the original reconstructed image can be separated by a minimum off-axis angle. In the design, we can also monitor and remove the negative effects of the reference tilt error in phase-shifting digital holography. Compared with the conventional digital holographic recording configuration, a supervising unit is introduced to control and to monitor the angle between the reference beam and object beam. By the Fourier analysis on the interferograms recorded by the supervising unit and using the corresponding equations, the off-axis angle, which is crucial to reset the object image in holographic reconstruction, can be calculated accurately and then chosen for the best recording angle. For in-line holography, the error affecting the slight tilt of the reference beam on the retrieved object wavefront can be eliminated completely because the tilt angle is detected by another independent device. Furthermore, by using this advanced design, the experimental arrangement can be transformed flexibly from the in-line recording state to the off-axis state or from the latter one to the former without rebuilding the experimental setup. The availability and effectiveness of this design are verified by a series of experiments.