Carcinoma of unknown primary (CUP) is a diagnostic and therapeutic challenge in oncology.The early and correct detection of the primary tumors of CUP is very important to its diagnosis, treatment, therapeutic response evaluation and prognosis prediction.This review summarizes the implications and development of the imaging technologies, especially 18F-FDG PET/CT scan, in the diagnosis, treatment and prognosis prediction of CUP patients.

The nanobody is a novel antibody fragment,which has beneficial biophysical and pharmacokinetic properties,such as the small molecular weight,high affinity and specificity for antigen.Nanobody is ideally suitable for molecular imaging as a targeting probe that could label antigen at nmol level in vitro.In animal models of xenografted tumor,atherosclerotic plaques and brain disorders,the target tissues were specifically and clearly detected and the high tumor-to-blood (T/B) ratios were obtained.Structural or chemical modified nanobodies will have higher affinity and retention to target tissues,and be convenient for the application of molecular imaging.With the development of the related research,nanobody-based molecular imaging will be gradually transformed into the clinical applications,and play an important role in early diagnosis and therapeutic assessment.

Optical imaging is one of the molecular imaging modalities,and it consists of three imaging methods (fluorescence,bioluminescence and diffusion imaging).For fluorescence imaging,quantum dots (QDs) are inorganic semiconductor nanocrystals with a diameter from 2 to 100 nm.Compared with organic fluorescent dye,QDs have several unique optical properties,such as wide and continuous excitation spectra,narrow and symmetrical emission spectrum,strong fluorescence intensity and high resistance to photobleaching.This article reviews the optical properties of QDs and their development in the field of molecular imaging from in vitro and in vivo applications,as well as the limitations and problems.

Early detection and accurate evaluation of vulnerable plaques is important to clinical prevention and in time intervention of atherosclerosis plaque rupture,which is the main reason of cardiovascular and cerebrovascular emergency events.Molecular imaging reveals the formation and progression mechanisms of atherosclerosis at the molecular level,and thus has obvious superiority in early detection and evaluation of vulnerable plaques.Suitable targets are the major contents of molecular probe research.Probes of different imaging modalities have been used to detect vulnerable plaques.The targets including low density lipoprotein,macrophage,adhesion molecule,micro calcification,activated protease,apoptosis,proliferation gene,integrin and thrombus.The mechanism of detecting different targets is different,and the effectiveness varies as well.This review summarizes the development of imaging probes for molecular detection of atherosclerosis vulnerable plaques.

Early diagnosis and accurate staging are important for planning therapeutic intervention to improve outcomes in patients with malignant melanoma (MM).Noninvasive molecular imaging has been extensively studied in cancer diagnosis,staging,therapeutic evaluation,and prognosis.Several radiopharmaceuticals have been developed to diagnose and treat MM,such as monoclonal antibodies,melanocortin receptors,benzamide (BZA) and BZA analogs.In this review,the characteristics and limitations of these radionuclide molecular probes are summarized and discussed.

To study the changes in every part of the beta-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups: IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1+, 2+, 3+ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the beta-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group (P < 0.001), while the enzymes were significantly higher in I/R (P < 0.001). The Bmax of beta-AR in IP was much higher than that in I/R (P < 0. 001), but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R (P < 0.05, 0.002 and 0.001, respectively). In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of beta-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA.
Ischemic Preconditioning, Myocardial ; Myocardium/*metabolism ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta/*physiology ; Signal Transduction

Fibroblast activation protein (FAP) is a marker protein of cancer-associated fibroblasts(CAFs). It is highly expressed in more than 90% of epithelial cancers and hardly expressed in normal tissues. Therefore, FAP is a very promising target. Radionuclide labeled FAP targeted molecular probes can be used for PET or SPECT imaging. In particular, 68Ga-FAP inhibitors (FAPIs) PET/CT has shown good prospects in the clinic, providing a new idea for early diagnosis, accurate staging and radionuclide treatment of tumors. In addition, FAP is also highly expressed in certain non-tumor diseases, especially those related to fibrosis. In this article, the research progress of radionuclide-labeled FAP targeted molecular probes is reviewed.

Cas9 is a RNA-guided double stranded DNA nuclease that participates in the CRISPR/Cas9 system. Wide-type Cas9 directly silences the expression of target gene by gene splicing. The engineered dCas9 protein with the mutation at D10A and H840A lacks the Cas9' s endonuclease function but keeps its DNA binding activity. dCas9 can activate special genes by fusing with transcription activator. Meanwhile,it can inhibit the gene transcription by directly binding to the target gene and stop gene transcrip?tion. Combination of light sensitive structures and CRISPR can produce light-inducible CRISPR/Cas9 system for control of gene expres?sion. This system is able to activate or inhibit gene expression via the use of controlling blue light(470 nm). In this review,we mainly discuss the development of the light inducible CRISPR/Cas9 system as well as its application in the control of gene expression.

Objective To evaluate the application value of 18 F‐FDG PET/CT in patients with fever of unknown origin (FUO) to improve the etiological diagnosis accuracy of PET/CT in patients with FUO and provide better service for clinical prac‐tice .Methods Clinical data and imaging results of 144 cases of FUO patients diagnosed through 18 F‐FDG PET/CT examination in Wuhan union hospital from December 2009 to December 2011 were retrospectively analyzed .The final diagnoses were based on sur‐gical pathology ,aspiration cytology ,or discharge diagnosis combined with more than 12 months of follow‐up results .All the PET/CT images were analyzed and the clinical application value of PET/CT in FUO patients were evaluated through the diagnose rate , diagnose efficiency and clinical staging of malignant tumor .Results Among the 144 patients ,there were 130 cases ultimately had clear diagnosis ,which including 41 cases of malignant tumor ,89 cases of benign lesions and 14 cases the cause of unknown .PET/CT detected abnormal lesions for 97 .6% (40/41) of patients with malignant lesions and 88 .7% (79/89) of patients with benign le‐sions ,and the diagnostic sensitivity ,specificity ,accuracy ,positive predictive value ,and negative predictive value were :97 .6% (40/41) ,86 .5% (77/89) ,90% (117/130) ,76 .9% (40/52) and 98 .7% (77/78) .PET/CT detected the primary lesions for the first time in 46 .3% (19/41) patients with malignant tumor ,and detected more lesions than the traditional imaging methods in 92 .7% (38/41) of these patients .Conclusion 18 F‐FDG PET/CT imaging can provided important reference value for the detection of primary lesions ,the qualitative diagnosis of benign and malignant lesions and clinical staging of malignant lesions .

Objective To identify the relationship among serum 25-hydroxyvitamin D[25(OH)D] level, chronic inflammation state and malnutrition in maintenance hemodialysis (MHD) patients. Methods The serum 25 (OH)D level of 119 patients on MHD was detected. All the patients were divided into three groups according to the serum 25(OH)D level. Vitamin D deficiency: 25(OH)D ≤ 15 ng/mL, vitamin D insufficiency: 15 ng/mL <25(OH)D ≤ 30 ng/mL, vitamin D normal: 25(OH)D > 30 ng/mL. Inflammatory factor and nutritive index were compared among the three groups. Result The average of serum 25 (OH)D level was 3.4~45.3 ng/mL (22.5~14.8 ng/mL), and the prevalence of 25 (OH)D deficiency and insufficiency was 88.2%. Significant differences existed in age, inflammatory factor (IL-6, TNF-α, CRP) and nutritive index (Alb, PA, SGA) between 25(OH)D deficiency, insufficiency groups and normal group (P<0.05). Conclusion The serum 25(OH)D level is possibly related to the malnutrition in MHD patients. It may inhibit chronic inflammation state , in which it can promote state of nutrition of MHD patients.