Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

OBJECTIVES: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. METHODS: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. RESULTS: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. CONCLUSIONS High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Prognosis ; Cell Proliferation ; Parathyroid Hormone-Related Protein/genetics* ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Signal Transduction ; Male ; RNA, Messenger/genetics* ; Female

The precise localization of pulmonary nodules has become an important technical key point in the treatment of pulmonary nodules by thoracoscopic surgery, which is a guarantee for safe margin and avoiding removal of too much normal lung parenchyma. With the development of medical technology and equipment, the methods of locating pulmonary nodules are also becoming less trauma and convenience. There are currently a number of methods applied to the preoperative or intraoperative localization of pulmonary nodules, including preoperative percutaneous puncture localization, preoperative transbronchial localization, intraoperative palpation localization, intraoperative ultrasound localization, and localization according to anatomy. The most appropriate localization method should be selected according to the location of the nodule, available equipment, and surgeon鈥檚 experience. According to the published literatures, we have sorted out a variety of different theories and methods of localization of pulmonary nodules in this article, summarizing their advantages and disadvantages for references.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Objective To investigate the role and underlying mechanisms of miR-34a/SIRT1 in intensive care unit acquired weakness(ICU-AW).Methods(1)C2C12 mouse skeletal muscle cells were induced to differentiate into myotubes,and were divided into two groups:model group[ICU-AW group,treated with lipopolysaccharides(LPS)for 12 hours]and normal control group(treated with the same amount of sterile water for 12 hours).Western blotting was used to detect the protein expression level of Muscle ring finger 1(MuRF-1),atrophy gene 1(Atrogin-1)and Sirtuin-1(SIRT1).RT-qPCR was used to assess the mRNA expression level of microRNA-34a(miR-34a),MuRF-1,Atrogin-1 and SIRT1,and light microscope was used to observe the growth and differentiation of C2C12 skeletal muscle cells in each group.(2)ICU-AW cells were further subdivided into control group(treated with siRNA transfection agent intervention),Scra siRNA group(treated with transfection agent and non-specific siRNA),miR-34a siRNA group(treated with transfection agent and specific siRNA intervention),vehicle group(treated with agonist solvent dimethyl sulfoxide)and SRT1720 group(treated with SIRT1 agonist SRT1720).Western blotting was used to detect the protein expression level of SIRT1,Atrogin-1 and MuRF-1 in each group.RT-qPCR was used to detect the miR-34a and the mRNA expression level of SIRT1,Atrogin-1 and MuRF-1 in each group.(3)In addition,another group of ICU-AW cells were divided into control group(treated with siRNA transfection),miR-34a siRNA group(treated with transfection agent and specific siRNA intervention),miR-34a siRNA+vehicle group(treated with transfection agent,specific siRNA and Dimethyl sulfoxide intervention)and miR-34a siRNA+EX-527 group(treated with transfection agent,specific siRNA and SIRT1 inhibitor EX-527).Western blotting was used to detect the protein expression level of Atrogin-1 and MuRF-1.RT-qPCR was used to assess the mRNA expression level of Atrogin-1 and MuRF-1.Results Myotube differentiation was observed on the 4th day.Compared with control group,myotube atrophy was obvious in ICU-AW group.RT-qPCR and Western blotting results revealed that,compared with normal control group,in ICU-AW group,the mRNA and protein expression levels of Atrogin-1 and MuRF-1 significantly increased(P＜0.05),and the expression level of miR-34a significantly increased(P＜0.05),while the mRNA and protein expression levels of SIRT1 significantly decreased(P＜0.05).RT-qPCR results showed that,compared with control group(treated with siRNA transfection agent intervention)and Scra siRNA group,the expression of miR-34a and mRNA expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group significantly decreased(P＜0.05),while the mRNA expression of SIRT1 significantly increased(P＜0.05),meanwhile the protein expression of Atrogin-1 and MuRF-1 decreased significantly(P＜0.01),and the protein expression of SIRT1 significantly increased(P＜0.05).RT-qPCR results also showed that,compared with vehicle group,the mRNA expression of Atrogin-1 and MuRF-1 in SRT1720 group decreased significantly(P＜0.05),while SIRT1 increased significantly(P＜0.05).Western blotting results demonstrated that,compared with control group and Scra siRNA group,the protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group decreased significantly(P＜0.05),while SIRT1 increased significantly(P＜0.05).RT-qPCR and Western blotting results indicated that,compared with miR-34a siRNA+vehicle group,the mRNA and protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA+EX-527 group increased significantly(P＜0.05).Conclusion Overactivation of miR-34a in ICU-AW contributes to skeletal muscle atrophy by inhibiting the expression of SIRT1,which may play an important role in the pathogenesis of ICU-AW.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective To develop a portable collection device of human exhaled breath condensate(EBC)based on natural breathing to meet the needs for rapid screening of human respiratory tract(especially lower respiratory tract)infections.Methods The device consisted of a refrigeration unit,a heat dissipation unit and a condensation unit.The refrigeration unit adopted a TES1-7102 thermoelectric Peltier cooler semiconductor as the refrigeration element;the heat dissipation unit was composed of a high thermal conductivity aluminum heat sink and a high-speed brushless cooling fan;the condensation unit was made up of a cold guide plate and a condenser,in which the cold guide plate was made of thin sheet of aluminum alloy,and the condenser was prepared by 3D printing technology and made of hydrophobic polylactic acid,with primary and secondary 2-stage guide grooves and an ultra-thin condensing surface.The performance of the device was verified in terms of cooling,thermal conductivity,condensation and human EBC collection and content analysis.Results Performance analysis showed that after refrigeration began the temperature difference between the condenser surface and the exhaled gas met the requirements of the condenser,and no obvious thermal resistance was found on the condensing surface so that large droplets could be formed rapidly and then be collected after the gas-liquid phase change of the exhaled gas on the condensing surface.Human EBC collection and content analysis indicated the device realized home self-collection of EBCs from people of all ages,and the concentrations of interleukins,C-reactive protein and other inflammation-related indexes and the pH value of the collected EBC samples were all correlated with respiratory infections in the subjects.Conclusion The device developed with easy operation avoids the discomfort of blowing collection and the risk of saliva contamination,and is worthy promoting for rapid diagnosis and dynamic monitoring of respiratory tract infection and other related diseases.[Chinese Medical Equipment Journal,2024,45(8):32-37]

Objective:To investigate the morphological difference and clinical significance of bilateral lumbar multifidus muscles in patients with unilateral lumbosacral radiculopathy due to lumbar disc herniation and lumbar spondylolisthesis.Methods:A retrospective analysis was conducted on patients with low back pain, lumbar disc herniation and lumbar spondylolisthesis. Patients with lumbar disc herniation or lumbar spondylolisthesis underwent single segment lesion either at L 4, 5 or L 5S 1, while those accompanied with unilateral lumbosacral radiculopathy underwent percutaneous endoscopic lumbar discectomy or conventional open surgery at Qingdao Municipal Hospital between January 2017 and January 2023. Patients with lumbar spondylolisthesis were subdivided into degenerative lumbar spondylolisthesis and isthmic spondylolisthesis. 53 patients with low back pain met the inclusion criteria. 170 patients with lumbar disc herniation met the inclusion criteria, with 101 at L 4, 5 and 69 at L 5S 1 level. 129 patients with lumbar spondylolisthesis met the inclusion criteria, including 91 of degenerative lumbar spondylolisthesis at L 4, 5 level and 9 at L 5S 1 level, and 11 of isthmic spondylolisthesis at L 4, 5 level and 18 at L 5S 1 level. Cross-sectional images at the mid-disc of L 3, 4, L 4, 5 and L 5S 1 segments in MRI were acquired. Relative total cross-sectional area (rTCSA), relative functional cross-sectional area (rFCSA), fat infiltration rate (FIR), relative fat distance (rFD) and differential value FIR (D-FIR) in bilateral lumbar multifidus muscle were measured respectively by using Image J software, and were then used to evaluate the atrophy and fat infiltration of bilateral lumbar multifidus muscles. Results:No significant difference was found between the both sides of multifidus muscle in low back pain patients. L 4, 5 lumbar disc herniation group had smaller rFCSA (0.34±0.10 and 0.35±0.10) and larger FIR [29.92(22.21, 36.46) and 26.48(17.54, 34.55)] and rFD [0.39(0.29, 0.54) and 0.32(0.21, 0.43)] on the affected side compared to the unaffected side in L 4, 5 segment, and had larger FIR (34.83±11.34 and 31.44±10.94) and rFD [0.59(0.43, 0.77) and 0.51(0.37, 0.69)] on the affected side in L 5S 1 segment. L 5S 1 lumbar disc herniation group had smaller rFCSA (0.41±0.11 and 0.42±0.12) and larger FIR [26.84(22.92, 35.29) and 24.02(20.03, 32.87)] and rFD (0.51±0.28 and 0.42±0.26) on the affected side in L 5S 1 segment. L 4, 5 degenerative lumbar spondylolisthesis group had larger FIR (36.49±9.76 and 34.72±9.86) on the affected side in L 4, 5 segment, and had larger FIR [35.03(28.64, 41.85) and 33.34(26.37, 39.76)] on the affected side in L 5S 1 segment. L 5S 1 degenerative lumbar spondylolisthesis group had larger FIR [42.53(37.94, 46.81) and 40.79(30.84, 43.53)] and rFD (1.12±0.79 and 0.94±0.79) on the affected side in L 5S 1 segment. L 4, 5 isthmic spondylolisthesis group had smaller rFCSA [0.24(0.20, 0.30) and 0.29(0.23, 0.34)]and larger FIR [34.19 31.30, 42.39) and 29.43(28.82, 36.89)] and rFD (0.39±0.15 and 0.29±0.15) on the affected side in L 4, 5 segment, and had larger FIR (43.18±12.71 and 34.12±11.63) on the affected side in L 5S 1 segment. L 5S 1 isthmic spondylolisthesis group had larger FIR (40.24±9.34 and 36.37±10.70) on the affected side in L 5S 1 segment. No significant difference was found of the multifidus muscle between the affected and unaffected sides in the proximal adjacent segment of the responsible segment in lumbar disc herniation or lumbar spondylolisthesis group patients. L 4, 5 isthmic spondylolisthesis group had larger D-FIR (6.75±8.46 and 1.78±5.77) in L 4, 5 segment, and had larger D-FIR (9.06±11.59 and 1.54±7.08) in L 5S 1 segment compared to L 4, 5 degenerative lumbar spondylolisthesis group. Grade Ⅱ L 4, 5 lumbar spondylolisthesis group had larger D-FIR (10.73±13.61 and 1.92±7.43) in L 5S 1 segment compared to grade Ⅰ L 4, 5 lumbar spondylolisthesis group. Conclusion:L 4, 5 or L 5S 1 lumbar disc herniation and lumbar spondylolisthesis patients with unilateral lumbosacral radiculopathy had asymmetric atrophy and fat infiltration of multifidus muscle. The atrophy and fat infiltration on the affected side showed greater. The asymmetry appeared in the responsible segment and its distal adjacent lumbar segment. Lumbar spondylolisthesis patients with a lager degree of slip or with isthmic type could be accompanied by more severe asymmetry of multifidus muscle.

Objective To analyze and study the prescriptions of Chief Physician Chang Yalin for treating breast hyperplasia patients in the outpatient department,explores and summarizes the medication patterns for treating breast hyperplasia,and provides reference and dialectical medication ideas for clinical treatment of breast hyperplasia by using data mining technology.Methods Collect the prescriptions of Dr.Chang Yalin for treating breast hyperplasia patients at the Outpatient Department of Jiuquan Traditional Chinese Medicine Hospital from January 1,2017 to December 31,2022.After induction and organization,establish a data table,use Excel 2019 to statistically analyze the drug frequency and gender,taste,and meridian.Use SPSS Modoler 18.0 software April algorithm to analyze the association rules of the drugs,and use SPSS Statistics for cluster analysis.Results A total of 184 prescriptions were included,covering 140 types of traditional Chinese medicine,with a total frequency of use of 4059 times.Among them,Cornus officinalis,dried ginger,roasted licorice,Poria cocos,and jujube are commonly used drugs for the treatment of breast hyperplasia.The top three types of Chinese medicine that are commonly used are tonifying deficiency,warming internal medicine,and relieving external symptoms.The medicinal properties are mainly warm and mild;The medicinal taste is characterized by sweetness,bitterness,and bitterness;The main meridians of drugs are spleen,lung,and heart meridians.Association rule analysis shows that roasted licorice white peony,poria cocos,licorice,and cornus flesh white peony,jujube,and ginger are equivalent.Classify commonly used drugs into 4 categories using Euclidean distance clustering and segmentation with 5.Conclusion Dr.Chang Yalin has always implemented the core idea of treating breast hyperplasia through the coordination of liver and spleen,the simultaneous application of attack and tonifying,and the simultaneous treatment of phlegm and blood stasis.In terms of the combination of latent drugs,the main focus is on tonifying qi and spleen,tonifying yin/blood and regulating liver,and resolving stasis/resolving phlegm and dispersing stagnation.In terms of the combination of"cold phlegm"and"blood stasis and toxin",as well as the combination of"eighteen contraindications"and"nineteen contraindications",his principles and methods are more distinctive and worthy of further research and promotion.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*