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.

ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

Objective:To investigate the clinicopathological characteristics and prognosis of pancreatic cancer (PC) patients with fatty pancreas (FP).Methods:The retrospective cohort study was conducted. The clinicopathological data of 116 patients with PC who underwent surgery at Qilu Hospital of Shandong University from January 2013 to January 2022 were collected. There were 85 males and 31 females, aged 60(54,65)years. Observation indicators: (1) clinicopathological characteristics of PC patients with FP; (2) influencing factors for FP in PC patients; (3) prognosis of PC patients with FP. Comparison of count data between groups was conducted using the Pearson chi-square test. Multivariate analysis was conducted using the Logistic regression model. The Kaplan-Meier method was used to plot survival curve and calculate survival rate, and Cox proportional hazard model was used for survival analysis.Results:(1) Clinicopathological characteristics of PC patients with FP. Of the 116 PC patients, there were 43 cases with FP and 73 cases without FP. Cases with tumor location at pancreatic head were 36 in PC patients with FP and 46 in PC patients without FP. Cases with tumor location at pancreatic body or tail were 7 in PC patients with FP and 27 in PC patients without FP. Cases with high-density lipoprotein cholesterol ≥1.04 mmol/L were 14 in PC patients with FP and 34 in PC patients without FP. Cases with dyslipidemia were 33 in PC patients with FP and 36 in PC patients without FP. There were significant differences in tumor location, high-density lipoprotein cholesterol and plasma lipid between PC patients with and without FP ( χ2=5.600, 4.588, 5.165, P<0.05). (2) Influencing factors for FP in PC patients. Results of multivariate analysis showed that no correlation was found between tumor location, high-density lipoprotein cholesterol, plasma lipid and FP in PC patients ( P>0.05). (3) Prognosis of PC patients with FP. Eighty of the 116 PC patients were followed up for 30.8(15.1,57.5)months, with the median overall survival time of 24.0 months. Among them, 54 patients with FP had a median overall survival time of 19.5 months, 26 patients without FP had a median overall survival time of 24.6 months, showing no significant difference in survival between them ( hazard ratio=1.031, P>0.05). Conclusions:There are differ-ences in tumor location, high-density lipoprotein cholesterol and plasma lipid between PC patients with and without FP, but no correlation is found between the above indicators and FP in PC patients. There is no significant difference in prognosis between patients with and without FP.

AIM To establish the near-infrared spectroscopy quantitative models for moisture,23-acetylalismol B and 23-acetylalismol C in Alismatis Rhizoma decoction pieces.METHODS The near-infrared spectroscopy(NIRS)data were collected in 95 batches of decoction pieces,after which drying method was adopted in the content determination of moisture,HPLC was applied to determining the contents of 23-acetylalismol B and 23-acetylalismol C,the quantitative models were established by partial least squares method combined with feature extraction algorithms.RESULTS The model training determination coefficients were 0.952 6,0.958 1 and 0.920 8,along with the prediction determination coefficients of 0.930 0,0.905 2 and 0.906 4,the residual prediction deviations(PRD)of 4.00,3.58 and 3.46,and the root mean square error ratios of prediction values to calibration values(RMSEP/RMSEC)of 1.15,1.11 and 1.06,respectively.CONCLUSION The quantitative models based on NIRS exhibit good prediction effects,which can be used for the rapid quality detection of Alismatis Rhizoma decoction pieces.

Objective To develop and validate a prediction model to identify high-risk individuals who are at-risk to develop acute liver injury(ALI)within 180 days in new statin users,and to support early clinical intervention.Methods Data were sourced from the Yinzhou Regional Health Information Platform,covering statin initiators aged 18 years and older from January 1,2010,to October 31,2021.The dataset was divided into a derivation cohort and a temporal validation cohort based on the time of statin initiation.Predictors were selected using LASSO regression,and the model was constructed using the extreme gradient boosting(XGBoost)algorithm combined with cost-sensitive learning.Model performance was evaluated using Brier scores,Harrell's C-index,and calibration curves.Results A total of 126,440 statin initiators were included,with 90,542 in the derivation cohort and 35,898 in the validation cohort.Within 180 days of initial statin use,412(0.33％)patients developed ALI,including 305(0.34％)in the derivation cohort and 107(0.30％)in the validation cohort.The final model incorporated 16 predictors,which included demographic characteristics,lifestyle factors,family history,medical history,statin use,and concomitant medication use.The model demonstrated excellent overall performance[Brier score=0.0043,95％CI(0.0038,0.0049)],discrimination[Harrell's C-index=0.761,95％CI(0.725,0.794)],and calibration in internal validation.In temporal validation,the model also performed well[Brier score=0.0044,95％CI(0.0036,0.0052),Harrell's C-index=0.703,95％CI(0.614,0.781)].Conclusion This study develope and validate a prediction model for ALI in statin users,providing clinicians with a reliable tool for individualized risk assessment.This model can help achieve risk stratification and reduce the occurrence of ALI.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Third-line treatment for metastatic colorectal cancer(mCRC)refers to subsequent therapeutic interventions following the failure or intolerance of first-and second-line treatments.This represents a critical challenge in clinical practice and a core focus of translational medicine research in recent years.With advancements in molecular typing technologies and the emergence of novel therapies,the third-line treatment strategy has evolved from traditional chemotherapy toward precision targeting and immunotherapy.A comprehensive literature search was conducted across PubMed,ClinicalTrials.gov database and American Society of Clinical Oncology(ASCO),European Society for Medical Oncology(ESMO)conference abstracts.Phase Ⅲ randomized controlled trials,phase Ⅰ/Ⅱ frontier clinical studies,and authoritative reviews were included,with an emphasis on data related to survival benefits,drug resistance mechanisms,and biomarkers.This review provided an in-depth analysis of significant progress in third-line treatment strategies for mCRC,encompassing standard therapies[regorafenib,fruquintinib,trifluridine/tipiracil,anti-epidermal growth factor receptor(EGFR)rechallenge therapy],targeted therapies(e.g.,BRAF V600E inhibitors,ERBB2 amplification inhibitors,KRAS G12C inhibitors)and immunotherapies[microsatellite instability-high(MSI-H)/deficient mismatch repair(dMMR),microsatellite stable(MSS)/proficient mismatch repair(pMMR)and target-immune combination therapies].Notable breakthroughs have been achieved in targeted therapies.Anti-EGFR rechallenge therapy extended the median overall survival(OS)to 17.3 months in RAS/BRAF wild-type patients identified through dynamic circulating tumor DNA(ctDNA)monitoring.However,drug resistance remains complex,with high secondary mutation rates necessitating further optimization of dynamic monitoring systems.For BRAF V600E mutations,triple therapy(encorafenib+binimetinib+cetuximab)demonstrated a median OS of 9.3 months[hazard ratio(HR)=0.52],surpassing conventional treatments.The combination of KRAS G12C inhibitor adagrasib with cetuximab achieved an objective response rate(ORR)of 34%and a median OS of 15.9 months,though tumor resistance continued to pose challenges.In the realm of immunotherapy,dual immunotherapy(nivolumab+ipilimumab)yielded a 4-year OS rate of 71%in MSI-H/dMMR patients.For MSS patients,immune-targeted combination strategies(e.g.,cabozantinib+atezolizumab)increased the ORR to 27.6%.Emerging therapies include artificial intelligence platforms for precision medicine,gut microbiota-based biomarkers and fecal microbiota transplantation,as well as advancements in chimeric antigen receptor-T(CAR-T)cell therapy.By summarizing the current status and progress of third-line treatment for mCRC,this review aims to inform clinical decision-making and guide future research directions.

Influenza(flu)is an acute respiratory infection caused by influenza viruses,characterized by high morbidity,strong trans-mission and general susceptibility of the population,and often accompanied by clinical symptoms such as fever,cough and muscle aches,etc.With the global pandemic of influenza,it has become a major challenge in the field of global public health,and therefore,it is particularly important to explore effective treatment methods.Chinese medicine has thousands of years of experience in treating in-fectious diseases and plays an important role in the prevention and treatment of influenza.This paper provides a comprehensive and systematic review of the Chinese medicine name,etiology,identification and typing,treatment methods and mechanism of action of in-fluenza,aiming to make up for the lack of the current summary of Chinese medicine treatment of influenza,with a view to providing cer-tain ideas and theoretical basis for the study of Chinese medicine treatment of influenza.

Objective:To perform RHD gene detection on a blood sample with serological weak D phenotype.Methods:A specimen received by the People's Hospital of Zhijin County was serologically identified by the microcolumn gel method and saline method.RHD gene detection was conducted by the PCR-SSP method,and the full sequence determination of the 10 exons amplified was performed.The sequencing results were compared with the ISBT database to determine the genotype.Bioinformatics tool was used to predict the functional damage of mutant proteins,and Alphafold-3 was used for tertiary structural modeling of wild-type and mutant RhD proteins,and the structures of the two proteins were compared and analyzed to explore the reasons why mutations lead to weak serological manifestations.Results:The patient's genotype was identified as RHD*DV.5/RHD*01N.01 heterozygote,with the complete deletion of RHD genes on one chromosome,unable to express the D antigen.On the other chromosome,a G＞A mutation occurred at the 697th base of the 5th exon,resulting in a partial D phenotype.This mutation causes internal hydrogen bond changes at the 233 position of RhD protein,resulting in a change in the conformation of the protein,affecting binding to the corresponding antibody.Conclusion:The patient is a heterozygous mutant individual with RHD*DV.5/RHD*01N.01,exhibiting a partial D phenotype serologically.This variation is extremely rare and has been scarcely reported globally.

Wound cleansing is an essential step in skin wound management. It can prevent local infection and optimize healing micro-environment by removing necrotic tissue and foreign matter, reducing microbial load, breaking bacterial biofilm formation and so on. Many randomized controlled trials and meta-analysis abroad have concluded that there is no significant difference in the incidence of wound infection and healing rate between the wounds irrigated with tap water and with sterile normal saline for skin wound cleansing. Considering the current requirements of medical fee policies in China, we recommend the use of tap water instead of saline or other wound cleansing solutions for cleansing skin wounds.