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.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Coronary artery calcification often appears a variety of complex lesions,increasing coronary intervention of the difficulty of treatment,especially the severe calcification lesions,usually cannot be fully dilated,resulting in a reduced success rate of surgery,an increased rate of acute stent thrombosis and restenosis,and even a serious impact on the prognosis of patients.Intravascular lithotripsy(IVL)is increasingly used in calcified lesions.There is more and more evidence of using in stable angina pectoris and unstable angina pectoris,but its use in acute ST-segment elevation myocardial infarction is limited,and only a few cases have been reported abroad.Moreover,the consensus of Chinese experts in the diagnosis and treatment of coronary artery calcification in 2021 edition lists thrombotic lesions as contraindications of shock wave balloon.This case is the first time in China to report the use of shock wave balloon in patients with acute ST elevation myocardial infarction complicated with thrombus.In this case,the patient with acute ST elevation myocardial infarction complicated with thrombus was severely under expanded stent after stent implantation,and obtain good curative effect using shockwave balloon at selected time in hospital after intensive anticoagulant therapy.

Coronary artery calcification often appears a variety of complex lesions,increasing coronary intervention of the difficulty of treatment,especially the severe calcification lesions,usually cannot be fully dilated,resulting in a reduced success rate of surgery,an increased rate of acute stent thrombosis and restenosis,and even a serious impact on the prognosis of patients.Intravascular lithotripsy(IVL)is increasingly used in calcified lesions.There is more and more evidence of using in stable angina pectoris and unstable angina pectoris,but its use in acute ST-segment elevation myocardial infarction is limited,and only a few cases have been reported abroad.Moreover,the consensus of Chinese experts in the diagnosis and treatment of coronary artery calcification in 2021 edition lists thrombotic lesions as contraindications of shock wave balloon.This case is the first time in China to report the use of shock wave balloon in patients with acute ST elevation myocardial infarction complicated with thrombus.In this case,the patient with acute ST elevation myocardial infarction complicated with thrombus was severely under expanded stent after stent implantation,and obtain good curative effect using shockwave balloon at selected time in hospital after intensive anticoagulant therapy.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

OBJECTIVE: To observe the effect of acupotomy on the fat infiltration degree of lumbar multifidus muscle (LMM) in patients with lumbar disc herniation after percutaneous transforaminal endoscopic discectomy (PTED). METHODS: A total of 104 patients with lumbar disc herniation treated with PTED were randomly divided into an observation group (52 cases, 3 cases dropped off) and a control group (52 cases, 4 cases dropped off). Patients of both groups received rehabilitation training of two weeks 48 h after PTED treatment. The observation group was treated with acupotomy (L₃-L₅ Jiaji [EX-B 2]) once within 24 h after PTED. In the two groups, the fat infiltration cross sectional area (CSA) of LMM was compared before and 6 months after PTED, the visual analogue scale (VAS) score and Oswestry disability index (ODI) score were observed before and 1, 6 months after PTED. The correlation between fat infiltration CSA of LMM in each segment and VAS score was analyzed. RESULTS: Six months after PTED, the fat infiltration CSA of LMM in L₄/L₅ and the total L₃-S₁ segments of the observation group was lower than that before PTED (P<0.05), and the fat infiltration CSA of LMM in L₄/L₅ of the observation group was lower than the control group (P<0.01). One month after PTED, the ODI and VAS scores of the two groups were lower than those before PTED (P<0.01), and those in the observation group were lower than the control group (P<0.05). Six months after PTED, the ODI and VAS scores of the two groups were lower than those before PTED and 1 month after PTED (P<0.01), and those in the observation group were lower than the control group (P<0.01). There was a positive correlation between the fat infiltration CSA of LMM in the total L₃-S₁ segments and VAS scores in the two groups before PTED (r = 0.64, P<0.01). Six months after PTED, there was no correlation between the fat infiltration CSA of LMM in each segment and VAS scores in the two groups (P>0.05). CONCLUSION Acupotomy can improve the fat infiltration degree of LMM, pain symptoms and activities of daily living in patients with lumbar disc herniation after PTED.
Humans ; Intervertebral Disc Displacement ; Activities of Daily Living ; Paraspinal Muscles ; Treatment Outcome ; Lumbar Vertebrae ; Retrospective Studies ; Endoscopy ; Diskectomy ; Acupuncture Therapy

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.

Branchial Region ; Branchioma/diagnosis* ; Humans ; Sleep ; Snoring

Estrogens/pharmacology* ; Humans ; Smell