ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

Abstract: To explore the relationship between the replication-associated bromodomain protein 4 ( BRD4)and human papillomavirus (HPV) 16(HPV16) viral load in cervical squamous cell carcinoma and CIN Ⅰ tissues , confirm the effects of BRD4 degradation agent MZ1 on viral load . Methods : Thirty HPV16-positive cervi- cal cancer specimens and 30 non-cervical cancer specimens were collected , and the viral load of the samples was detected by real-time fluorescence quantitative PCR , and the expression of BRD4 was analyzed by immunohisto- chemistry and Western blot. Results : The viral load was higher in the samples of cervical cancer group than in the samples of non-cancer group , the difference is statistically significant ( P < 0. 01) . Immunohistochemistry results showed that the expression of BRD4 were significantly higher in cervical cancer specimens than in noncancerous specimens , the difference is statistically significant (P < 0. 05) . BRD4 expression was significantly and positively correlated with high viral loads , the difference is statistically significant (P < 0. 001) . the BRD4 degradation agent MZ1 significantly reduced the viral load , the difference is statistically significant (P < 0. 01) . Conclusion BRD4 may be involved in the replication of HPV16 virus , and BRD4 degradation agent MZ1 can inhibit the replication of HPV16 virus .

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female ; Humans ; Infant ; Disorder of Sex Development, 46,XY/genetics* ; Leydig Cells/pathology* ; Mutation ; Receptors, LH/genetics* ; Testis/abnormalities*

The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*

Objective To investigate the correlation between maternal serum folic acid(FA),monocyte chemoattractant protein-1(MCP-1),progesterone-induced blocking factor(PIBF)levels and embryonic development cessation in early pregnancy.Methods From December 2021 to December 2023,98 pregnant women with embryonic development cessation in early pregnancy admitted to the Second Hospital of Jingzhou were regarded as the cessation group,and 50 normal early pregnancy pregnant women who underwent pregnancy examinations during the same period were as the control group.General clinical data was collected and analyzed.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of FA,MCP-1 and PIBF.Multivariate logistic regression was applied to analyze the influencing factors of early pregnancy embryo cessation of development.Receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of serum FA,MCP-1,and PIBF for early embryonic development cessation in pregnancy.Pearson method was applied to analyze the correlation between serum FA,MCP-1,PIBF,progesterone(PROG),estradiol(E2)and β-human chorionic gonadotropin(β-HCG).Results Compared with the control group,the serum FA(9.51±1.21 nmol/L vs 11.32±1.56 nmol/L)and PIBF(295.46±30.22 ng/ml vs 342.14±36.97 ng/ml)levels in the cessation group were greatly reduced,while the serum MCP-1(1.02±0.15 mg/ml vs 0.82±0.11 mg/ml)level was greatly increased,and the differences were statistically significant(t=7.785,8.347,8.229,all P＜0.001).There were great statistical differences in the history of embryonic development cessation(75.64%vs 25.36%),PROG(13.32±1.81 ng/ml vs 23.65±2.74 ng/ml),E2(221.34±25.69 pmol/L vs 298.65±31.64 pmol/L),and β-HCG levels(5 323.62±536.85U/L vs 8 562.31±924.55 U/L)between the two groups(t/χ2=6.548～27.428,all P<0.05).Pregnant women's history of embryonic development cessation and elevated level of MCP-1 were risk factors for embryonic development cessation in early pregnancy(Wald χ2=4.239,4.613,all P<0.05),while elevated levels of β-HCG,FA and PIBF were protective factors for embryonic development cessation in early pregnancy(Wald χ2=4.476,4.423,5.974,all P<0.05).The AUC of FA,MCP-1,PIBF,and their combination in predicting early embryonic development cessation in pregnancy was 0.811,0.805,0.816 and 0.908,respectively.The combined prediction was greatly better than that of individual diagnosis of FA MCP-1,and PIBF(Z=2.749,2.381,1.993,all P<0.05).FA and PIBF were positively correlated with PROG,E2 and β-HCG(r=0.433～0.512,all P<0.05),while MCP-1 was negatively correlated with PROG,E2 and β-HCG(r=-0.432,-0.487,-0.458,all P<0.05).Conclusion The serum levels of FA and PIBF in pregnant women with embryonic development cessation in early pregnancy decrease,while the level of MCP-1 increases.These three factors are all influencing factors for embryonic development cessation in pregnant women,and have certain auxiliary predictive value for embryonic development cessation in early pregnancy.

Objective To analyze the characteristics,causes,influencing factors of compensation,and appraisal features of second-instance medical malpractice cases involving cardiovascular diseases in Henan Province from 2017 to 2022,and to provide reference for forensic appraisal and judicial trial.Methods Cases were retrieved from China Judgments Online between 2017 and 2022.A total of 1,957 documents were reviewed,including 1,397 medical malpractice cases and 130 cardiovascular disease cases.Results The total compensation awarded in these second-instance cases was 27.04 million yuan,with a median of 158,600 yuan.Cases involving patient death accounted for 80.00％(104/130).Among 107 cases with first-instance appraisals,55.14％(59/107)raised objections,while 74.62％(97/130)of the second-instance trials upheld the original judgment.The most common degree of responsibility borne by medical institutions was secondary responsibility(41.54％,54/130).The top three medical faults were:inadequate observation and management of patient conditions(46.15％),omission of auxiliary examinations(37.50％),and insufficient notification(36.54％).In terms of violations-including medical record documentation,inappropriate treatment,misdiagnosis or missed diagnosis,out-of-scope practice,and improper medication use-the actual proportions in judgments(24/113,34/113,12/113,7/113,14/113)were all significantly lower than the patients' claims(all P＜0.05).Conclusion Cardiovascular medical malpractice cases in second-instance trials involve substantial compensation and a high proportion of death outcomes.Both medical institutions and patients should pay greater attention to first-instance trials.Appraisal organizations should proactively provide explanation and education regarding issues likely to raise patient doubts,thereby reducing unnecessary appeals.They should also avoid hasty revisions of appraisal opinions when faced with objections and instead focus on improving the quality and credibility of appraisals.In determining medical faults,emphasis should be placed on evaluating whether there was inadequate patient monitoring and management,omission of auxiliary examinations,and insufficient notification.

Objective:To compare the efficacy of O-arm navigation versus C-arm guidance for anterior internal fixation in the management of Anderson-D′Alonzo type II odontoid fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 58 patients with Anderson-D′Alonzo type II odontoid fractures admitted to Zhengzhou Orthopedic Hospital between January 2017 and September 2024, including 35 males and 23 females, aged 18-57 years [(39.3±9.0)years]. Anderson-D′Alonzo type II fractures were further classified as type IIA in 25 patients and type IIB in 33. Twenty-seven patients underwent O-arm assisted anterior internal fixation (O-arm navigation group), while 31 received C-arm guided anterior internal fixation (C-arm guidance group). The two groups were compared in terms of the operative duration, intraoperative blood loss, success rate for one-time guidewire placement, and intraoperative radiation exposure (anteroposterior and lateral views). At 3 days postoperatively, screw placement accuracy was evaluated via CT in both groups. Additionally, neck disability index (NDI) and visual analogue scale (VAS) scores were assessed preoperatively, at 1 week, 3 months postoperatively, and at the last follow-up. Bone union time and complication rate were also analyzed.Results:All the patients were followed up for 6-20 months [(13.1±3.4)months]. The O-arm navigation group exhibited significantly shorter operative duration [(91.1± 8.9)minutes] and less intraoperative blood loss [(38.9±8.2)ml], compared with (103.3±14.5)minutes and (47.3±9.1)ml in the C-arm guidance group ( P<0.01). The success rate for one-time guidewire placement was 100% (27/27) in the O-arm navigation group, significantly higher than 52% (16/31) in the C-arm guidance group ( P<0.01). Intraoperative radiation exposure for patients in the O-arm navigation group was lower in both anteroposterior view [(11 612.6±1 603.6)μSv] and lateral views [(29 738.2±6 602.5)μSv], compared with (40 638.0±9 431.9)μSv and (47 152.0±11 759.3)μSv in the C-arm guidance group ( P<0.01). CT scans at 3 days postoperatively revealed a 100% (27/27) screw placement accuracy in the O-arm navigation group, compared with 65% (20/31) in the C-arm guidance group ( P<0.01). Before operation, at 1 weeks and 3 months postoperatively, and at the last follow-up, NDI scores were (48.4±7.8)%, (21.0±3.1)%, (14.4±2.4)%, and (13.9±2.3)% in the O-arm navigation group, while they were (47.4±7.6)%, (20.9±3.2)%, (14.1±2.0)%, and (13.8±1.4)% in the C-arm guidance group ( P>0.05); VAS scores were 6.0(6.0, 7.0)points, 4.0(3.0, 4.0)points, 2.0(1.0, 2.0)points, and 2.0(1.0, 2.0)points in the O-arm navigation group, while they were 7.0(6.0, 7.0)points, 4.0(3.0, 5.0)points, 2.0(1.0, 3.0)points, and 2.0(2.0, 2.0)points in the C-arm guidance group ( P>0.05). The NDI and VAS scores in both groups were significantly improved at 1 weeks and 3 months postoperatively, and at the last follow-up compared to those preoperatively ( P<0.05), and were furtherly improved at 3 months postoperatively and at the last follow-up compared to those at 1 weeks postoperatively ( P<0.05), with no significant differences between those at 3 months postoperatively and at the last follow-up ( P>0.05). No significant difference was found in bone union time between the two groups ( P>0.05). The complication rate in the O-arm navigation group was 4% (1/27), lower than 29% (9/31) in the C-arm guidance group ( P<0.05). Conclusions:Compared with C-arm guidance, O-arm assisted anterior internal fixation for Anderson-D′Alonzo type II odontoid fractures can reduce operative duration and intraoperative blood loss, improve the success rate for one-time guidewire placement and screw accuracy, and decrease radiation exposure and complication rate.

Objective:To compare the efficacy of whole-process visualization system-assisted pedicle screw internal fixation and free-hand pedicle screw internal fixation in the treatment of thoracolumbar burst fracture (TLBF) without neurologic symptoms.Methods:A retrospective cohort study was conducted to analyze the clinical data of 64 patients with TLBF without neurologic symptoms admitted to Zhengzhou Orthopedic Hospital from December 2020 to October 2022, including 41 males and 23 females, aged 23-52 years [(42.1±6.6)years]. The injured vertebrae involved T 11 in 26 patients, T 12 in 17, L 1 in 12, and L 2 in 9. The Wiltse approach was used in all the patients, 31 of whom were treated with pedicle screw internal fixation assisted by the whole-process visualization system (visualization system-assisted screw placement group) and 33 of whom were treated with free-hand pedicle screw internal fixation (free-hand screw placement group). The two groups were compared in terms of operation time, single screw placement time, intraoperative blood loss, intraoperative total radiation dose and total length of hospital stay. The accuracy of pedicle screw placement and penetration rate of the pedicle cortex were evaluated in the two groups. The Cobb angle and lumbar visual analogue scale (VAS) before surgery, at 1 week, 3 months after surgery and at the last follow-up were compared between the two groups. The incidence of postoperative complications was also investigated. Results:All the patients were followed up for 10-33 months [(17.5±4.8)months]. The operation time was (106.9±11.8)minutes in the visualization system-assisted screw placement group, shorter than (121.3±11.4)minutes in the free-hand screw placement group ( P<0.01). The single screw placement time was (9.1±1.0)minutes in the visualization system-assisted screw placement group, shorter than (11.7±1.5)minutes in the free-hand screw placement group ( P<0.01). The total radiation dose was (10.4±2.4)mGy in the visualization system-assisted screw placement group, lower than (51.8±7.2)mGy in the screw placement group ( P<0.01). There was no significant difference in intraoperative blood loss or total length of hospital stay between the two groups ( P>0.05). The accuracy of pedicle screw placement was 96.6% (197/204) in the visualization system-assisted screw placement group, significantly higher than 89.3% (191/214) in the free-hand screw placement group ( P<0.01). Both groups showed significant improvements in Cobb angle and VAS scores at 1 week, 3 months after surgery, and at the last follow-up ( P<0.05). There were no significant differences in Cobb angle or VAS scores between the two groups at each time point ( P>0.05). In the visualization system-assisted screw placement group, one patient had incision infection at 4 days after operation, which was cured with antibiotics. One patient in the free-hand screw placement group developed the symptoms of nerve root irritation at 2 days after surgery, which disappeared at 7 days after revision. There was no significant difference in the incidence of complications between the two groups ( P>0.05). During the follow-up, no patients had broken screws, loosening of internal fixation, or loss of correction in either group. Conclusions:Compared with free-hand pedicle screw internal fixation, the whole-process visualization system-assisted pedicle screw internal fixation in the treatment of TLBF without neurologic symptoms can shorten the time of operation and screw placement, reduce the radiation dose, and improve the accuracy of pedicle screw placement, suggesting that it is a safer and more effective auxiliary method for pedicle screw placement.