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.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Azoospermia factor c (AZFc) microdeletion is one of the most common genetic factors of male infertility, presenting with different clinical phenotypes, including oligozoospermia and azoospermia. With the development of assisted reproductive technologies such as microdissection testicular sperm extraction, intracytoplasmic sperm injection and preimplantation genetic testing, patients with AZFc microdeletion have gained the opportunity to have their own biological offspring. However, some patients still experience suboptimal outcomes from assisted reproduction treatments. The key factors contributing to these poor outcomes remain unclear. This review summarizes recent advances in the diagnosis and treatment of male infertility caused by AZFc deletions, aiming to provide a reference for clinical work and look forward to future research ideas in this field.

Objective:To analyze the proportion of nonobstructive azoospermia(NOA)patients opting for sperm bank donation under different sperm retrieval methods[percutaneous testicular sperm aspiration(TESA),microdissection testicular sperm extraction(mTESE)]and its influencing factors.Methods:Retrospective data from assisted reproductive technology(ART)cycles at the Center for Reproductive Medical,Peking University Third Hospital(from January 2019 to December 2023)were collected.Data-complete ART cycles involving NOA patients and their partners(using the last treatment cycle as the endpoint)were selected.Sperm donation utilization rates were compared across retrieval methods(fresh mTESE,fresh TESA,thawed mTESE,thawed TESA).Log-linear models were used to analyze the rela-tionship between sperm retrieval method and sperm source.Results:Among the 1 730 couples,the over-all sperm donation utilization rate was 12.66％.The highest rate occurred in the fresh mTESE group(23.42％),followed by the thawed mTESE group(5.87％).The rates for the fresh TESA and thawed TESA groups were 5.22％and 0％,respectively.Log-linear analysis demonstrated that sperm retrieval method was significantly associated with sperm source(mTESE:Estimate=4.499;TESA:Estimate=2.780;P＜0.001).Conclusion:The low overall sperm donation utilization rate in ART cycles may re-flect the efficacy of synchronous sperm retrieval ART.The proportion of NOA patients opting for sperm donation was influenced by the retrieval method.Compared with patients undergoing TESA,those under-going mTESE were more inclined to utilize donor sperm after retrieval failure.

Objective:To analyze the clinical features and pathogenic genes of a family with congenital cataracts.Methods:A pedigree analysis was performed.A Han Chinese family initially diagnosed with congenital cataracts at The Fourth Hospital of Shijiazhuang in March 2024 was enrolled.The proband and selected family members underwent detailed ophthalmic examinations.Potential cataract-associated genetic variants in the proband were identified using whole exome sequencing (WES). Sanger sequencing was employed to confirm the presence of these variants in the proband and other family members.The identified variants were analyzed in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG). This study adhered to the Declaration of Helsinki.The research protocol was approved by the Ethics Committee of The Fourth Hospital of Shijiazhuang (No.20230074). Both the subjects and their guardians were informed of the study purpose and voluntarily signed the informed consent form.Results:The pedigree included four generations comprising 15 individuals, with three patients identified across the second, third, and fourth generations.These cases included two males and one female, specifically the proband, his mother, and his eldest son.The observed inheritance pattern aligned with an autosomal dominant mode, characterized by the clinical presentation of bilateral cataracts.WES identified a novel frameshift insertion variant c. 270_271insA in exon 2 of the CRYAB gene in the proband, resulting in a valine-to-serine substitution at amino acid position 91.This variant induced early termination of translation following the expression of two additional amino acids, loss of 84 amino acids (p.V91Sfs2) and the production of a functionally impaired protein.The Sanger sequencing validation results were consistent with the co-segregation.According to the ACMG classification criteria (PM2+ PP1+ PVS1), the variant was classified as likely pathogenic. Conclusions:The frameshift insertion variant c. 270_271insA (p.V91Sfs2) in exon 2 of the CRYAB gene is likely the pathogenic cause of congenital cataract in this family.This is the first report of this variant.

Objective:To investigate the clinical manifestations, long-term survival, and prognosis of childhood T-cell acute lymphoblastic leukemia (T-ALL).Methods:Case summary.The clinical data of 43 T-ALL children who were diagnosed and treated in Children′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2010 to December 2021 were retrospectively analyzed.They were stratified for treatment according to the CCCG-ALL regimen, and the correlation of prognosis with the condition at initial diagnosis, early treatment response, and induced remission was analyzed.The Kaplan-Meier survival curve was used to analyze the survival rate, and the survival rates were compared between groups by the Log-rank test.The multivariate Cox regression model was used to analyze the impact of multiple factors on the long-term survival of children.Results:T-ALL patients accounted for 9.5% (43/451) of the total number of acute lymphoblastic leukemia patients admitted to the hospital at the same period.The median onset age of the 43 T-ALL patients was 7 years (1-13 years).Of the 43 patients included, 14 patients (32.6%) had concomitant mediastinal widening, 8 patients (18.6%) had concomitant giant mediastinal masses, and 4 patients (9.3%) had early precursor T-cell acute lymphoblastic leukemia (ETP-ALL) at initial diagnosis.These 43 children were treated according to the CCCG-ALL intermediate- and high-risk group regimen.Among them, 33 children (76.7%) achieved sustained remission, 5 children died, and 5 children had a relapse.As of September 30, 2024, the median follow-up time was 62 months (1-170 months), the 10-year event-free survival rate was (80.2±6.4)%, and the 10-year overall survival rate was (86.6±5.8)%.The median relapse time and 10-year cumulative relapse rate of the 5 relapsed children were 28 months (7-58 months) and (13.7±5.8)%, respectively.The relationship of prognosis with clinical characteristics at initial diagnosis and induced remission in 43 T-ALL children was analyzed.The results showed that patients aged ≥10 years, with a grade-1 non-central nervous system at initial diagnosis, ETP-ALL, abnormal chromosome number and structure, non-M1 status of bone marrow and minimal residual disease (MRD)≥ 1% on day 19 of induction treatment, and MRD ≥ 0.01% on day 46 to 55 of induction treatment had poorer long-term survival(all P<0.05).The multivariate analysis showed that age ≥10 years, ETP-ALL, and abnormal chromosome number and structure were risk factors of poor prognosis ( P=0.045, 0.030, 0.021). Conclusions:The CCCG-ALL regimen has a good overall therapeutic effect in children with T-ALL.Age ≥10 years, abnormal chromosome number and structure, ETP-ALL, grade-1 non-central nervous system at initial diagnosis, and early remission are risk factors of poor prognosis.Treatment after relapse in children with T-ALL is difficult.

Antibody-drug conjugates (ADCs) are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker. Currently, 15 ADCs have been clinically approved worldwide. More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs. ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development. It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells, thereby producing promising antitumor efficacy and favorable adverse effect profiles. However, emergence of drug resistance has severely hindered the clinical efficacy of ADCs. In this review, we introduce the structure and mechanism of ADCs, describe the development of ADCs, summarized the latest research about the mechanisms of ADC resistance, discussed the strategies to overcome ADCs resistance, and predicted biomarkers for treatment response to ADC, aiming to contribute to the development of ADCs in the future.

OBJECTIVES: To investigate the mechanism underlying the therapeutic effect of electroacupuncture (EA) on post-traumatic stress disorder (PTSD) in rats. METHODS: Forty male SD rats were randomized equally into blank control group, PTSD model group, sham-acupuncture group, paroxetine group, and EA group. In the latter 3 groups, the rat models of PTSD, induced by continuous single-prolonged stress and plantar electrical stimulation, were treated with EA at GV20, GV24, BL18 and BL23 acupoints for 15 min (5 times a week for 3 weeks), sham-acupuncture without electrical stimulation, or gavage with paroxetine suspension on the same schedule. Behavioral changes of the rats were evaluated using open field test (OFT) and elevated plus maze (EPM) test. Hippocampal pathologies and neuronal changes were examined with HE and Nissl staining, and mitochondrial ultrastructure was examined using electron microscopy. The mRNA and protein expression levels of Bcl-2, Bax, and caspase-3 were detected by RT-qPCR and immunofluorescence staining. RESULTS: The rat models of PTSD showed significantly reduced total distance traveled in OFT and distance and time spent in the open arms of the EPM, with decreased hippocampal neurons, obvious neuronal and mitochondrial pathologies, decreased hippocampal expression of Bcl-2, and increased Bax and caspase-3 expressions. Treatments with paroxetine and EA both significantly improved behavioral changes of the rat models, increased the number of Nissl-stained neurons, obviously alleviated pathologies in the hippocampal neurons and mitochondrial ultrastructure, increased hippocampal Bcl-2 expression, and lowered caspase-3 expressions. Paroxetine showed significantly better effect than EA for improving performance of the rats in EPM test, whereas sham-acupuncture did not produce any significant improvement. CONCLUSIONS EA alleviates PTSD in rats possibly by upregulating Bcl-2 and downregulating Bax and caspase-3, thereby ameliorating hippocampal mitochondrial damage.
Animals ; Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Hippocampus/pathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Mitochondria/pathology* ; Signal Transduction ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Disease Models, Animal