ObjectivePhotoacoustic tomography (PAT) holds significant potential for high-resolution deep-tissue imaging. In preclinical research, custom-designed concave arc-shaped ultrasound transducer arrays are often used to maximize the detection aperture. However, manufacturing limitations and assembly tolerances frequently cause the actual physical positions of array elements to deviate from their theoretical design. Additionally, concave arrays are typically covered with an acoustic lens, which introduces a mismatch in the speed of sound between the coupling medium and the lens material. The combination of these geometric and acoustic-phase errors leads to severe image artifacts, reduced contrast, and degraded resolution. This study proposes a systematic two-step calibration strategy to address these issues and substantially improve image quality. MethodsFirst, a high-intensity isotropic photoacoustic point source was constructed using a multi-mode optical fiber coated with carbon nanotubes (CNTs) to acquire high signal-to-noise ratio calibration data. The Akaike information criterion (AIC) was employed to accurately determine the time of arrival (ToA) of photoacoustic signals. Subsequently, a geometric calibration algorithm based on nonlinear least-squares (NLS) estimation was developed. This algorithm iteratively solves for the true spatial coordinates of each array element by minimizing the residual between theoretical and measured acoustic path lengths. To further address sound-speed inhomogeneity caused by the acoustic lens, a phase compensation algorithm based on bilinear interpolation was proposed. This algorithm computes a pixel-specific phase delay map across the imaging region and performs point-by-point signal correction during delay-and-sum (DAS) reconstruction. The proposed methods were validated using a custom 96-channel concave arc-shaped array (center frequency: 12  MHz) through both phantom imaging and in vivo mouse tumor models. ResultsPhantom experiments showed that at an imaging depth of14 mm, the reconstruction position deviation of the point source in the uncalibrated system reached up to 1  mm. After applying the combined calibration, the lateral resolution (full width at half maximum, FWHM) at the focal point of the arc array reached 95  μm—representing a 85% reduction compared to the uncalibrated state and a 79% reduction compared to geometric calibration alone without phase compensation. In vivo experiments demonstrated that the calibrated system clearly resolved the microvascular network of subcutaneous tumors in mice. Photoacoustic signals were strictly confined within tumor boundaries delineated by ultrasound imaging (USI), eliminating the vascular spillover artifacts commonly observed in uncalibrated images. Furthermore, after intravenous injection of indocyanine green (ICG), the system successfully detected weak photoacoustic signals at a depth of 5 mm, performing significantly better than the uncalibrated system. ConclusionThe proposed calibration method, which integrates nonlinear least-squares estimation with phase compensation, significantly improves image fidelity and spatial resolution consistency across a wide field of view by correcting systemic geometric errors and acoustic phase aberrations. This approach demonstrates high robustness and provides a reliable technical foundation for the clinical translation of photoacoustic probes with non-standard geometries.

AIM:Fine particulate matter(PM2.5)is closely associated with airway hyper-responsiveness(AHR).However,the underlying mechanism by which PM2.5 leads to AHR is still unclear.This study aimed to investi-gate the respiratory effects of ambient PM2.5 exposure.METHODS:Forty mice were randomly divided into five groups:control group(intranasal saline),lipopolysaccharide(LPS)group(100 mg/L),PM2.5 low-dose group(0.003 5 mg/d),PM2.5 medium-dose group(0.007 mg/d),and PM2.5 high-dose group(0.014 mg/d).They were treated with intranasal in-stillation for 30 d.Lung function and tracheal contractile responses were evaluated using whole-body plethysmography and sensitive wire myograph.Inflammatory mediators in serum and oxidative stress parameters were detected using enzyme-linked immunosorbent assay(ELISA).Lung tissues were subjected to HE and Masson staining.RT-qPCR and Western blot were used to determine the expression of contractile receptors and the phosphorylation of the mitogen-activated protein kinase(MAPK)signal pathway.RESULTS:Intranasal instillation of PM2.5 significantly increased airway resistance in mice and enhanced tracheal contractility in response to carbachol.PM2.5 elevated levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in serum.PM2.5 instillation also led to a decrease in glutathione peroxidase(GSH-Px)levels and an increase in malondialdehyde(MDA)levels.Lung tissue exhibited notable pathological changes,including inflammatory cell infiltration,hyperplasia of alveolar epithelial cells,and collagen deposition.Mechanistically,exposure to PM2.5 increased the expression of muscarinic M3 receptor mRNA and protein,as well as the phosphorylation of p-ERK1/2 and p-p38 proteins following PM2.5 instillation.CONCLUSION:Intranasal instillation of PM2.5 induced inflammation and oxidative stress,along with the activation of the extracellular signal-regulated kinase 1/2(ERK1/2)and p38 MAPK pathways,resulting in the upregulation of M3 receptor-induced AHR.

The development of surgery brings about the transformation of surgeons′ con-cepts, and in turn, each renewal of surgical concepts propels progress of surgical techniques. These two aspects complement each other. The treatment of hepatocellular carcinoma is a comprehensive therapy centered on surgery. With the deepening understanding of liver anatomy, the surgical methods have evolved from initial local resection to anatomical liver resection, and then to resection of the tumor-bearing portal vein territory. In recent years, with the emergence of hepatic membrane anatomy, portal plate theory, and three-dimensional visualization, the theoretical and technical systems of laparoscopic anatomical liver resection has become more and more mature. Based on own experience and literature reports, the authors systematically elaborate on the construction of theoretical and technological systems of laparoscopic anatomic liver resection for hepatocellular carcinoma, for reference by colleagues.

Objective To explore the electroencephalography(EEG)characteristics of patients with knee osteoarthritis(KOA)which are different from those of healthy subjects during dynamic balance tests,and study the connection and influence between brain activity and KOA.Methods Fifteen patients with KOA and 17 healthy subjects performed the timed up and go test(TUGT)and five times sit-to-stand test(5STS).The EEG characteristics of the 4 frequency bands,namely δ(0.5-4 Hz),θ(4-8 Hz),α(8-14 Hz)and β(14-30 Hz)of 9 electrodes including CZ,C3,C4 in the central region,PZ,P3,P4 in the parietal lobe,and OZ,O1,O2 in the occipital lobe of the cerebral cortex of the subjects were recorded.Time and frequency domain analysis were conducted.Results During 5STS,the time-domain amplitudes of electrodes C4,P3,and P4 in the δ band,electrodes C4,P3,and P4 in the θ band,and electrodes P3 and P4 in the β band of KOA patients were significantly higher than those of healthy subjects(P<0.05);the power of EEG signals of electrodes P3,P4,and O2 in the β band was significantly higher than that of healthy subjects.During TUGT,except that the time-domain amplitude of electrode PZ in the θ band of KOA patients was significantly lower than that of healthy subjects(P<0.05),there was no significant difference in all electrodes in other frequency bands;the power of EEG signals of electrodes C3,CZ,C4,PZ,P4,O1,OZ,O2 in the δ band and electrodes CZ,P3,PZ,and OZ in the α band and electrodes CZ,P4,OZ,and O2 in the β band was significantly lower than that of healthy subjects(P<0.05).Conclusions Compared with healthy subjects,the activity in the parietal lobe area of the brain of KOA patients during 5STS was stronger,while the brain activity in the central region,parietal lobe,and occipital lobe areas of KOA patients during TUGT was weaker than that of healthy subjects.This study may provide some references for clinicians in the prevention and treatment of KOA.

OBJECTIVE To provide a reference for standardizing the conduct of positron-emitting radiopharmaceuticals'phase 0 clinical trials(hereinafter referred to as"phase 0 clinical trials")and advancing the development of innovative drug by medical institutions.METHODS Initiated by the First Affiliated Hospital of Jinan University,a panel of experts consisting of pharmacy,clinical medicine and medical ethics from multiple institutions was established to investigate the current landscape,and discuss the necessary conditions,procedures,and other aspects for conducting phase 0 clinical trials in medical institutions by integrating relevant national policies,regulations and expert consensus.Finally,an agreement was reached to formulate this consensus.RESULTS&CONCLUSIONS Currently,most medical institutions have deficiencies in pharmaceutical care during the management of radiopharmaceuticals and the phase 0 clinical trials.In conjunction with the Expert Consensus on the Establishment of Nuclear Pharmacist Positions,this consensus explicitly defines the responsibilities of nuclear pharmacists in the phase 0 clinical trials on the basis of the Expert Consensus for the Application of Positron Emission Tomography Radioligands for Translational Study in the Phase 0 Clinical Trials(2020 edition),providing a guidance for high-quality participation of nuclear pharmacists from medical institutions in China in phase 0 clinical research.Additionally,in consideration of some constraints imposed by current relevant regulations,this consensus also proposes strategic recommendations,such as encouraging medical institutions to form a consortium,leading to the establishment of dedicated bases or industrial parks,holding significant implications to strengthen institutional capacity for advancing radiopharmaceutical innovation through phase 0 clinical trials.

Objective To compare the effectiveness of the heart rate variability threshold(HRVT),muscle oxygenation threshold(MOT),and their combined threshold(COMT)in predicting the ventila-tory threshold(VT)and lactate threshold(LT).Methods Twenty male athletes at or above the nation-al level were recruited to perform an incremental exercise test to determine VT and LT,during which gas exchange,muscle oxygenation,and heart rate variability were collected.The HRVT,MOT,and COMT methods were then applied,and their predictive validity was evaluated by comparing the correla-tions and agreements between heart rate(HR)and power output(PO)at VT and LT.Results For HR,VT1 showed strong correlation and agreement with MOT1(r=0.958,ICC=0.944)and COMT1(r=0.957,ICC=0.951),with COMT1 having the smallest mean bias(1.4 bpm)and the narrowest limits of agreement(LOA)(-5.4 to 8.2 bpm).Moreover,VT2 demonstrated the highest correlation and agree-ment with COMT2(r=0.985,ICC=0.982),with a mean bias of-0.7 bpm and LOA of-5.0 to 3.7 bpm.Meanwhile,LT showed high correlation and good agreement with COMT2(r=0.884,ICC=0.754)and MOT2(r=0.886,ICC=0.738),with mean biases of-6.8 bpm and-7.3 bpm,and LOA of-17.5 to 3.8 bpm and-17.9 to 3.2 bpm,respectively.For PO,VT1 had the best correlation and agreement with MOT1(r=0.836,ICC=0.808),with a mean bias of-0.2 W and LOA of-11.7 to 11.3 W.VT2 performed best correlation and agreement with COMT2(r=0.910,ICC=0.900),with a mean bias of 2.3 W and LOA of-8.9 to 13.5 W.In LT prediction,MOT2(r=0.736,ICC=0.692)outperformed COMT2(r=0.635,ICC=0.618),with mean biases of-2.6 W and 0.2 W,and LOA of-26.0 to 20.7 W and-26.6 to 27.1 W,respectively.Conclusion All three indicators—HRVT,MOT,and COMT—demonstrates high validity in predicting VT and LT.MOT1 performs best for predicting PO at VT1,while COMT2 shows the highest consistency for predicting both HR and PO at VT2.Howev-er,for LT prediction,MOT2 is more advantageous for predicting PO,whereas COMT2 is more accu-rate for predicting HR.Therefore,method selection should be tailored to the specific threshold type and measurement target.

Objective To explore the electroencephalography(EEG)characteristics of patients with knee osteoarthritis(KOA)which are different from those of healthy subjects during dynamic balance tests,and study the connection and influence between brain activity and KOA.Methods Fifteen patients with KOA and 17 healthy subjects performed the timed up and go test(TUGT)and five times sit-to-stand test(5STS).The EEG characteristics of the 4 frequency bands,namely δ(0.5-4 Hz),θ(4-8 Hz),α(8-14 Hz)and β(14-30 Hz)of 9 electrodes including CZ,C3,C4 in the central region,PZ,P3,P4 in the parietal lobe,and OZ,O1,O2 in the occipital lobe of the cerebral cortex of the subjects were recorded.Time and frequency domain analysis were conducted.Results During 5STS,the time-domain amplitudes of electrodes C4,P3,and P4 in the δ band,electrodes C4,P3,and P4 in the θ band,and electrodes P3 and P4 in the β band of KOA patients were significantly higher than those of healthy subjects(P<0.05);the power of EEG signals of electrodes P3,P4,and O2 in the β band was significantly higher than that of healthy subjects.During TUGT,except that the time-domain amplitude of electrode PZ in the θ band of KOA patients was significantly lower than that of healthy subjects(P<0.05),there was no significant difference in all electrodes in other frequency bands;the power of EEG signals of electrodes C3,CZ,C4,PZ,P4,O1,OZ,O2 in the δ band and electrodes CZ,P3,PZ,and OZ in the α band and electrodes CZ,P4,OZ,and O2 in the β band was significantly lower than that of healthy subjects(P<0.05).Conclusions Compared with healthy subjects,the activity in the parietal lobe area of the brain of KOA patients during 5STS was stronger,while the brain activity in the central region,parietal lobe,and occipital lobe areas of KOA patients during TUGT was weaker than that of healthy subjects.This study may provide some references for clinicians in the prevention and treatment of KOA.

OBJECTIVE: To preliminarily investigate the effects and mechanism of action of Yishen Yangsui Formula (, YSYSF)on the recovery of neurological function in rats with degenerative cervical myelopathy. METHODS: Fifty adult SD female rats were randomly divided into control group, sham group, model group, YSYSF group and positive drug group by using randomized numerical table method. In the model group, YSYSF group and positive drug group, polyvinyl alcohol acrylamide interpenetrating network hydrogel(water-absorbent swelling material) was used to construct a rat spinal cord chronic compression model. The sham group was implanted with the water-absorbent swelling material and then removed without causing spinal cord compression. The control group, the sham group and the model group were given equal amounts of saline by gavage, the group of YSYSF was given Chinese herbal medicine soup by gavage 9.1 g·kg^-1 once a day, and the positive drug group was given tetrahexylsalicylglucoside sodium monosialate ganglioside by intraperitoneal injection 4.2 mg·kg^-1 once a day. The motor function of the rats was assessed by the BBB method after 1, 3, 7, and 14 d of drug administration. The spinal cord tissues were taken from rats executed 14 d after drug administration, and the morphological changes of the spinal cord compression site were observed by HE staining, and the expression levels of Caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 were detected in the area of spinal cord injury by Western blot method. RESULTS: The BBB scores of the control group and the sham group were normal at all time points after modeling, which were higher than the BBB scores of the model group, the YSYSF, and the positive drug group (P<0.05). From the 3rd day after gavage, at all time points, the BBB scores of rats in the YSYSF group and the positive drug group were higher than those of rats in the model group (P<0.05). The staining pattern of HE spinal cord tissue was normal in the control group and the sham group, and the HE spinal cord in the model group was severely damaged with a large number of neuron deaths, whereas the damage to the spinal cord and neuron cells was reduced in the YSYSF group and the positive drug group. The expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β and IL-18 in the spinal cord of the model group were significantly higher than those of the sham group (P<0.0001), and the expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 in the YSYSF group and the drug group were significantly lower than those in the model group (P<0.05). CONCLUSION YSYSF can improve the motor function of rats with degenerative cervical spinal cord disease, alleviate the pathological changes, and promote the recovery of spinal cord neurological function. The specific mechanism may be related to the inhibition of the activation of inflammatory vesicles NLRP3 and PYCARD, the reduction of the release of inflammatory factors IL-1β and IL-18, the reduction of the expression of caspase-1 and GSDMD, the reduction of cellular death, and the inhibition of inflammatory response.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Pyroptosis/drug effects* ; Spinal Cord/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Spinal Cord Diseases/drug therapy* ; Interleukin-1beta/metabolism*

Objective To compare the effectiveness of the heart rate variability threshold(HRVT),muscle oxygenation threshold(MOT),and their combined threshold(COMT)in predicting the ventila-tory threshold(VT)and lactate threshold(LT).Methods Twenty male athletes at or above the nation-al level were recruited to perform an incremental exercise test to determine VT and LT,during which gas exchange,muscle oxygenation,and heart rate variability were collected.The HRVT,MOT,and COMT methods were then applied,and their predictive validity was evaluated by comparing the correla-tions and agreements between heart rate(HR)and power output(PO)at VT and LT.Results For HR,VT1 showed strong correlation and agreement with MOT1(r=0.958,ICC=0.944)and COMT1(r=0.957,ICC=0.951),with COMT1 having the smallest mean bias(1.4 bpm)and the narrowest limits of agreement(LOA)(-5.4 to 8.2 bpm).Moreover,VT2 demonstrated the highest correlation and agree-ment with COMT2(r=0.985,ICC=0.982),with a mean bias of-0.7 bpm and LOA of-5.0 to 3.7 bpm.Meanwhile,LT showed high correlation and good agreement with COMT2(r=0.884,ICC=0.754)and MOT2(r=0.886,ICC=0.738),with mean biases of-6.8 bpm and-7.3 bpm,and LOA of-17.5 to 3.8 bpm and-17.9 to 3.2 bpm,respectively.For PO,VT1 had the best correlation and agreement with MOT1(r=0.836,ICC=0.808),with a mean bias of-0.2 W and LOA of-11.7 to 11.3 W.VT2 performed best correlation and agreement with COMT2(r=0.910,ICC=0.900),with a mean bias of 2.3 W and LOA of-8.9 to 13.5 W.In LT prediction,MOT2(r=0.736,ICC=0.692)outperformed COMT2(r=0.635,ICC=0.618),with mean biases of-2.6 W and 0.2 W,and LOA of-26.0 to 20.7 W and-26.6 to 27.1 W,respectively.Conclusion All three indicators—HRVT,MOT,and COMT—demonstrates high validity in predicting VT and LT.MOT1 performs best for predicting PO at VT1,while COMT2 shows the highest consistency for predicting both HR and PO at VT2.Howev-er,for LT prediction,MOT2 is more advantageous for predicting PO,whereas COMT2 is more accu-rate for predicting HR.Therefore,method selection should be tailored to the specific threshold type and measurement target.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.