Integrin αvβ3 is an important target for tumor imaging and therapy. It is highly expressed on tumor neovascular endothelial cells and various malignant tumor cells， while being nearly absent in normal tissues and quiescent endothelial cells. Positron emission tomography （PET） based on Arg-Gly-Asp （RGD） peptides has been widely applied， yet single-target strategies are limited by tumor heterogeneity. β^- radionuclide-labeled RGD peptides exhibit problems of insufficient tumor uptake and renal accumulation. This review summarizes the preclinical progress in two frontier directions. Dual-targeting strategies combine integrin αvβ3 with prostate-specific membrane antigen （PSMA） or fibroblast activation protein （FAP） to construct heterodimeric probes. Preclinical and clinical studies have demonstrated that dual-targeting probes achieve significantly superior tumor uptake， target-to-background ratios， and lesion detection rates compared to single-target controls， effectively overcoming tumor heterogeneity and improving tumor uptake and detection rate. α radionuclides， by leveraging high linear energy transfer and short tissue range， demonstrate superior antitumor efficacy over β^-radionuclides. In terms of clinical translation， the albumin-binding RGD dimer labeled with lutetium-177 （¹⁷⁷Lu-AB-3PRGD₂） has completed a first-in-human study， preliminarily validating the clinical feasibility of integrin-targeted radionuclide therapy， albeit with limited antitumor activity. Future directions include molecular imaging-based patient selection， optimization of dual-targeting molecular structures， and development of α radionuclide formulations.

Integrin αvβ3 is an important target for tumor imaging and therapy. It is highly expressed on tumor neovascular endothelial cells and various malignant tumor cells， while being nearly absent in normal tissues and quiescent endothelial cells. Positron emission tomography （PET） based on Arg-Gly-Asp （RGD） peptides has been widely applied， yet single-target strategies are limited by tumor heterogeneity. β^- radionuclide-labeled RGD peptides exhibit problems of insufficient tumor uptake and renal accumulation. This review summarizes the preclinical progress in two frontier directions. Dual-targeting strategies combine integrin αvβ3 with prostate-specific membrane antigen （PSMA） or fibroblast activation protein （FAP） to construct heterodimeric probes. Preclinical and clinical studies have demonstrated that dual-targeting probes achieve significantly superior tumor uptake， target-to-background ratios， and lesion detection rates compared to single-target controls， effectively overcoming tumor heterogeneity and improving tumor uptake and detection rate. α radionuclides， by leveraging high linear energy transfer and short tissue range， demonstrate superior antitumor efficacy over β^-radionuclides. In terms of clinical translation， the albumin-binding RGD dimer labeled with lutetium-177 （¹⁷⁷Lu-AB-3PRGD₂） has completed a first-in-human study， preliminarily validating the clinical feasibility of integrin-targeted radionuclide therapy， albeit with limited antitumor activity. Future directions include molecular imaging-based patient selection， optimization of dual-targeting molecular structures， and development of α radionuclide formulations.

ObjectiveTo investigate the mechanism underlying the weight loss effect of electrothermal acupuncture （ETA） in diet-induced obese （DIO） model mice based on the hypoxia-inducible factor-1α （HIF-1α）/sphingosine-1-phosphate （S1P）sphingosine-1-phosphate receptor 3 （S1PR3） signaling pathway-mediated macrophage polarization. MethodsAn obesity mouse model was established by continuously feeding at a high-fat diet （HFD） for 8 weeks. Twenty successfully modeled obese mice were randomly divided into a model group and an electrothermal acupuncture （ETA） group with 10 mice per group， both of which continued to receive the HFD till week 12. Another 10 mice were assigned to the normal group and fed a standard chow diet continuously for 12 weeks. Starting from week 9 of the experiment， mice in the ETA group received electrothermal acupuncture stimulation at Zhongwan （CV12）， bilateral Tianshu （ST25）， and bilateral Zusanli （ST36） for 30 minutes per session， with the instrument current set at （40±0.5）mA and a constant temperature of （40±0.5）℃. Mice in the normal group and the model group were restrained in the same manner for 30 minutes without acupuncture. All interventions were performed once every other day for a total of 4 weeks. Ten hours after the final intervention， the body weight， waist circumference， and body length of mice in each group were measured， and Lee's index was calculated. Serum biochemical analysis was performed to assess fasting blood glucose （FBG）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （Cr）. Serum leptin （LEP） and adiponectin （ADPN） levels， as well as sphingosine-1-phosphate （S1P） levels in epididymal white adipose tissue （eWAT）， were detected by ELISA. Histomorphological changes in eWAT were monitored via HE staining. Flow cytometry was used to analyze macrophage subtype-related indexes in eWAT， including the total proportion of macrophages， the proportion of M1 macrophages， the proportion of M2 macrophages， and the M1/M2 ratio. Antibody array technology was used to determine the levels of differentially expressed inflammatory factors in eWAT between the model and blank groups， as well as between the ETA and model groups. Western blot and qPCR were used to detect the protein and mRNA expression levels of HIF-1α and S1PR3 in the eWAT， respectively. ResultsCompared to the normal group， the model group showed significantly increased body weight， Lee's index， waist circumference， and FBG， TC， TG， HDL-C， LDL-C， AST， and ALT levels， upgraded LEP and S1P levels， decreased ADPN level and ADPN/LEP ratio， elevated proportion of M1 macrophages and the M1/M2 ratio， reduced proportion of M2 macrophages， and upregulated protein and mRNA expression levels of HIF-1α and S1PR3 （P＜0.05 or P＜0.01）. With the exception of HDL-C， all the abovementioned indicators in the ETA group were significantly improved compared to the model group （P＜0.05 or P＜0.01）. Analysis of differentially expressed inflammatory cytokines revealed that， compared to the normal group， the levels of interleukin-1β （IL-1β）， interferon-γ （IFN-γ）， interleukin-6 （IL-6）， and interleukin-12p70 （IL-12p70） in the eWAT of the model group were elevated； conversely， the levels of interleukin-17 （IL-17）， interleukin-5 （IL-5）， IL-6， and interleukin-23 （IL-23） in the eWAT of the ETA group decreased compared to the model group （P＜0.05 or P＜0.01）. ConclusionETA exerts a weight-reducing effect in obese model mice， and the mechanism may involve inhibition of the HIF-1α/S1P/S1PR3 signaling pathway activation， which shifts macrophage polarization from the M1 to M2 phenotype， thereby alleviating chronic inflammation.

Objective:To investigate the influence of ultrasonic monitoring of bladder filling levels on setup errors before fractionated radiotherapy for cervical cancer patients through a comparative analysis, and its effectiveness in improving clinical target volume (CTV) margins.Methods:A retrospective study was conducted on 1 284 error data of setup via cone beam CT (CBCT) and 6D setup error correction system from 172 cervical cancer patients treated in the Radiotherapy Department of Peking University Cancer Hospital from January 2019 to October 2023. These patients were classified into two groups: 87 (659 times of setup) with ultrasonic monitoring of bladder filling levels and 85 (625 times of setup) without ultrasonic monitoring. The setup errors, error distributions, and numbers of abnormal setups between the two groups were compared in the lateral (Lat), longitudinal (Lng), vertical (Vrt), pitch (Pitch), roll (Roll), and rotational (Rtn) dimensions. Moreover, the CTV to planning target volume(PTV) margin values in the three-dimensional direction were calculated for both groups to assess the clinical value of ultrasonic monitoring of bladder filling levels before fractionated radiotherapy.Results:Compared to the group without ultrasonic monitoring, the group with ultrasonic monitoring exhibited lower median values of setup errors in all six-dimensional directions and smaller upper and lower interquartile ranges ( Z = -10.86 to -6.34, P<0.05). The group with ultrasonic monitoring manifested more concentrated setup errors in various directions and statistically significantly reduced numbers of abnormal setups ( χ2=15.33, P<0.05). Moreover, CTV-PTV margins of the group with ultrasonic monitoring displayed reduced CTV-PTV margin values by 0.55, 1.52, and 1.26 mm in the Vrt, Lng, and Lat directions, respectively. Conclusions:Pre-radiotherapy ultrasonic monitoring of bladder filling levels in cervical cancer patients can significantly improve the repeatability of setup, thus notably reducing the incidence of abnormal setups. Theoretically, it can narrow the range from the CTV to the PTV, thereby minimizing radiation exposure to healthy tissues and ultimately enhancing radiotherapy precision for cervical cancer and reducing radiation damage.

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.

Objective:To investigate the influence of ultrasonic monitoring of bladder filling levels on setup errors before fractionated radiotherapy for cervical cancer patients through a comparative analysis, and its effectiveness in improving clinical target volume (CTV) margins.Methods:A retrospective study was conducted on 1 284 error data of setup via cone beam CT (CBCT) and 6D setup error correction system from 172 cervical cancer patients treated in the Radiotherapy Department of Peking University Cancer Hospital from January 2019 to October 2023. These patients were classified into two groups: 87 (659 times of setup) with ultrasonic monitoring of bladder filling levels and 85 (625 times of setup) without ultrasonic monitoring. The setup errors, error distributions, and numbers of abnormal setups between the two groups were compared in the lateral (Lat), longitudinal (Lng), vertical (Vrt), pitch (Pitch), roll (Roll), and rotational (Rtn) dimensions. Moreover, the CTV to planning target volume(PTV) margin values in the three-dimensional direction were calculated for both groups to assess the clinical value of ultrasonic monitoring of bladder filling levels before fractionated radiotherapy.Results:Compared to the group without ultrasonic monitoring, the group with ultrasonic monitoring exhibited lower median values of setup errors in all six-dimensional directions and smaller upper and lower interquartile ranges ( Z = -10.86 to -6.34, P<0.05). The group with ultrasonic monitoring manifested more concentrated setup errors in various directions and statistically significantly reduced numbers of abnormal setups ( χ2=15.33, P<0.05). Moreover, CTV-PTV margins of the group with ultrasonic monitoring displayed reduced CTV-PTV margin values by 0.55, 1.52, and 1.26 mm in the Vrt, Lng, and Lat directions, respectively. Conclusions:Pre-radiotherapy ultrasonic monitoring of bladder filling levels in cervical cancer patients can significantly improve the repeatability of setup, thus notably reducing the incidence of abnormal setups. Theoretically, it can narrow the range from the CTV to the PTV, thereby minimizing radiation exposure to healthy tissues and ultimately enhancing radiotherapy precision for cervical cancer and reducing radiation damage.

ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

Differentiated thyroid cancer(DTC)accounts for more than 95％of all thyroid cancers.99Tcm-3PRGD2 can specifically bind to integrin αvβ3 receptors highly expressed on the surfaces of neovascular endothelial cells and tumor cells in malignant tumors.With high specificity and safety,99Tcm-3PRGD2 can not only be used for diagnosing DTC and its metastases,but also evaluating the efficacy of anti-angiogenic and anti-αvβ3 therapies.99Tcm-MIBI is a non-specific tumor-avid imaging agent,which may improve diagnostic accuracy combined with 99Tcm-3PRGD2.The research progresses of 99Tcm-3PRGD2 and 99Tcm-MIBI for diagnosis and treatment of DTC were reviewed in this article.

Differentiated thyroid cancer(DTC)accounts for more than 95％of all thyroid cancers.99Tcm-3PRGD2 can specifically bind to integrin αvβ3 receptors highly expressed on the surfaces of neovascular endothelial cells and tumor cells in malignant tumors.With high specificity and safety,99Tcm-3PRGD2 can not only be used for diagnosing DTC and its metastases,but also evaluating the efficacy of anti-angiogenic and anti-αvβ3 therapies.99Tcm-MIBI is a non-specific tumor-avid imaging agent,which may improve diagnostic accuracy combined with 99Tcm-3PRGD2.The research progresses of 99Tcm-3PRGD2 and 99Tcm-MIBI for diagnosis and treatment of DTC were reviewed in this article.

ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg^-1） group， and low- and high-dose （8.4 and 33.6 g·kg^-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.