Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Tujia ethnic group medicine Xuetong is derived from Kadsura heteroclita, the stem of which has the medicinal value for anti-rheumatoid arthritis, liver protection, anti-tumor, anti-oxidation effects, and has been widely used in Hunan and Guangdong in China. The selection of reliable and stable reference genes is the basis for subsequent molecular research on K. heteroclita. In this study, GAPDH, TUA, Actin, UBQ, EF-1α, 18S-rRNA, CYP, UBC, TUB, H2A, and RPL were selected as candidate reference genes in Kadsura heteroclita. The gene expression levels of the 11 candidate reference genes of K. heteroclita in its 6 different parts(stem-inside of the cambium, stem-outside of the cambium, fruit, flower, root, and leaf) and under different intervention conditions [drought stress, salt stress, and methyl jasmonate(MeJA) treatment] were detected by quantitative real-time polymerase chain reaction(qRT-PCR). The expression stability of the 11 candidate reference genes was comprehensively analyzed and evaluated by geNorm, NormFinder, ΔCT algorithm, and RefFinder software. The results showed that the expression of UBC and RPL was relatively stable in 6 different parts, and UBC and GAPDH genes were relatively stable under different intervention conditions. To verify the reliability of reference genes for K. heteroclita, this study further examined the relative expression levels of KhFPS, KhIDI, KhCAS, KhSQE, KhSQS, KhSQS-2, KhHMGS, KhHMGR, KhMVD, KhMVK, KhDXR, KhDXS, KhPMVK, and KhGGPS in different parts and under different intervention conditions, which might relate to the synthesis of the main component(Xuetongsu) of K. heteroclita. The results showed that with UBC and RPL or UBC and GAPDH as the reference genes, the expression trends of these 14 genes were basically consistent in different parts or under different intervention conditions for K. heteroclita. In conclusion, UBC can be used as a reference gene of K. heteroclita for its different parts and different intervention conditions, which lays a foundation for further research on the biosynthetic pathway of main components in K. heteroclita.
Real-Time Polymerase Chain Reaction/methods* ; Reference Standards ; Gene Expression Regulation, Plant ; Gene Expression Profiling ; Plant Proteins/metabolism* ; Drugs, Chinese Herbal

BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.

Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Objective To evaluate the stability,safety and immune enhancement and anti-tumor effects of Wilms'tumor gene 1(WT1)peptide combined with AddaVaxTM emulsion vaccine for acute myeloid leukemia.Methods The stability of WT1 peptide in the adjuvant vaccine was evaluated using MALDI-TOF-MS time-of-flight mass spectrometry.Female C57BL/6 mice were randomly divided into PBS group,WT1 peptide group,and WT1 peptide+AddaVaxTMemulsion adjuvant vaccine group.The immunization was performed at a dose of 50 μg/mouse for antigen and 50 μg/mouse for adjuvant,with intramuscular injection on days 0,14,and 28.HE staining was used to assess the toxicity of intramuscular vaccination on mouse organ tissues.Cytokine levels were detected by ELISA,and the number of IFN-γ-secreting splenocytes was measured by ELISpot.Flow cytometry was employed to detect the maturation of bone marrow-derived dendritic cells(BMDCs)promoted by the vaccine in vitro and the promotion for lymphocyte activation,and H-2Db WT1 tetramer was utilized to detect the proportion of specific CD8+T cells.After establishing a mouse leukemia tumor model using the C1498-mWT1 stable cell line,the anti-tumor effects of the vaccine for prevention and treatment were evaluated.Results The WT1 peptide stably existed in the vaccine without causing significant organ tissue changes in mice after intramuscular injection.Compared to the mice immunized with WT1 aqueous solution,the mice after intramuscular injection of the WT1 peptide emulsion adjuvant vaccine showed stronger immune responses of Th1 cells,including IFN-γ and TNF-α,as well as Th17 cells of IL-17A(P＜0.05),and the mice had not only promoted number of IFN-γ secreting splenocytes(P＜0.01)but also enhanced maturation of BMDCs,as indicated by an increase in the proportions of CD40+/CD11c+and CD86+CD80+/CD11c+ cells(P＜0.05).Additionally,there were increases in both the proportion of CD4+/CD3+T and CD69+/CD8+T cells(P＜0.05)and the proportion of specific CD8+T cells(P＜0.05).In the anti-tumor effect study using the C1498-mWT1 mouse model,the median survival time of the WT1+AddaVaxTM group was extended by 6 d compared to the WT1 aqueous solution group.At day 50,the survival rate of mice in the WT1+AddaVaxTM group was still 28.5％,while all mice in the other groups had died(P＜0.05).Conclusion The vaccine with the WT1 peptide and AddaVaxTM emulsion adjuvant exhibits good immunological and anti-tumor effects.

To understand the pathogenicity,virulence genes,drug resistance genes,and drug resistance of Staphylococcus aureus isolated from yaks in some areas of Lhasa and Nagqu City,55 yak nasal swab samples were analyzed for S.aureus in this study.The cocci were isolated and identified,and the carriage of virulence genes and drug resistance genes,as well as the pathogenicity and drug sensitivity of the isolated S.aureus strains,were detected with PCR,artificially infected mice,and the K-B drug susceptibility disk method.Seven strains of S.aureus were isolated from the 55 yak nasal swab samples,with an iso-lation rate of 12.73％.The isolated strains were all pathogenic to mice,with a fatality rate exceeding 60％.These seven strains of S.aureus carried three drug resistance genes(tetM,tet,and mecA)and six virulence genes(seb,sec,clfA,hla,hlb,and nuc).The detection rate of the three drug resistance genes was 100％,whereas the detection rate of the six virulence genes in the isolates ranged from 83.33％to 100％.The resistance rates of the isolated strains to penicillin,ampicillin,and cotrimox-azole reached 85.71％-100％,whereas the resistance rates to tetracycline and ceftazidime were both 28.57％.Thus,yaks in Lhasa and Nagqu cities were found to be infected by S.aureus strains carrying various drug-resistance genes and virulence genes.These strains were highly pathogenic and showed sensi-tivity to most antibacterial drugs.These findings may serve as a reference for treating S.aureus infection in yaks in the cities of Lhasa and Nagqu.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To investigate the clinical value of thromboelastogram in early diagnosis of deep vein thrombosis (DVT) in patients undergoing free flap surgery of lower extremity.Methods:A retrospective study was conducted to analyze the 192 patients undergoing surgical repair of soft tissue defects at lower extremity with free anterolateral femoral flap at Department of Orthopaedics, Tongji Hospital from January 2018 to June 2022. There were 117 males and 75 females, with an age of (45.6±12.7) years and an area of skin defects ranging from 5 cm × 3 cm to 18 cm × 9 cm. The patients were divided into 2 groups according to whether DVT occurred on the first day after surgery. In the DVT group of 22 patients, there were 14 males and 8 females, with an age of (47.7±14.3) years; in the DVT-free group of 170 patients, there were 103 males and 67 females, with an age of (45.3±12.5) years. The 2 groups were compared in terms of reaction time, coagulation time, maximum amplitude and coagulation angle in the thromboelastogram. Diagram of receiver operating characteristic (ROC) curves was used to evaluate the predictive value of thromboelastography in assessing the risk of DVT after surgery.Results:The 2 groups were comparable because there was no significant difference in the baseline information or operation time between them ( P>0.05). The reaction time [(5.21±0.85) min] and coagulation time [(1.12±0.30) min] in the DVT group were significantly shorter than those in the DVT-free group [(6.48±0.06) min and (1.60±0.03) min], and the maximum amplitude [(71.45±1.17) mm] and coagulation angle [69.54° (64.59°, 76.64°) ] in the DVT group were significantly larger than those in the DVT-free group [(66.63±0.40) mm and 64.92°(54.11°, 74.21°)] (all P<0.05). The optimal cut-off points in the ROC diagram were 5.46 min at reaction time, 1.52 min at coagulation time, 72.31 mm at maximum amplitude and 59.89° at coagulation angle. The sensitivity and specificity of detecting DVT on the first day after surgery were 80.7% and 71.6%, respectively, according to the combination of the best cut-off points in the ROC diagram and all the indexes in the thromboelastogram. Conclusion:Thromboelastogram is of a great value for the diagnosis of lower extremity DVT, and of a positive significance for the prevention of serious complications after surgery in patients undergoing free flap surgery of lower extremity.

Objective:To explore the prognostic predictive value of deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis of ST-elevated myocardial infarction (STEMI) patients after successful percutaneous coronary intervention(PCI).Methods:A retrospective analysis was performed in 97 STEMI patients with thrombolysis in myocardial infarction-3 flow in infarct vessel after primary PCI in Renmin Hospital of Wuhan University from June to November 2021. MCE was performed within 48 h after PCI. Patients were followed up to 120 days. The adverse events were defined as cardiac death, hospitalization for congestive heart failure, reinfarction, stroke and recurrent angina. The framework consisted of the U-net and hierarchical convolutional LSTMs. The plateau myocardial contrast intensity (A), micro-bubble rate constant (β), and microvascular blood flow (MBF) for all myocardial segments were obtained by the framework, and then underwent variability analysis. Patients were divided into low MBF group and high MBF group based on MBF values, the baseline characteristics and adverse events were compared between the two groups. Other variables included biomarkers, ventricular wall motion analysis, MCE qualitative analysis, and left ventricular ejection fraction. The relationship between various variables and prognosis was investigated using Cox regression analysis. The ROC curve was plotted to evaluate the diagnostic efficacy of the models, and the diagnostic efficacy of the models was compared using the integrated discrimination improvement index (IDI).Results:The time-cost for processing all 3 810 frames from 97 patients was 377 s. 92.89% and 7.11% of the frames were evaluated by an experienced echocardiographer as "good segmentation" and "correction needed". The correlation coefficients of A, β, and MBF ranged from 0.97 to 0.99 for intra-observer and inter-observer variability. During follow-up, 20 patients met the adverse events. Multivariate Cox regression analysis showed that for each increase of 1 IU/s in MBF of the infarct-related artery territory, the risk of adverse events decreased by 6% ( HR 0.94, 95% CI =0.91-0.98). There was a 4.5-fold increased risk of adverse events in the low MBF group ( HR 5.50, 95% CI=1.55-19.49). After incorporating DNN-assisted MCE quantitative analysis into qualitative analysis, the IDI for prognostic prediction was 15% (AUC 0.86, sensitivity 0.78, specificity 0.73). Conclusions:MBF of the area supplied by infarct-related artery after STEMI-PCI is an independent protective factor for short-term prognosis. The DNN-assisted MCE quantitative analysis is an objective, efficient, and reproducible method to evaluate microvascular perfusion. Assessment of culprit-MBF after PCI in STEMI patients adds independent short-term prognostic information over qualitative analysis.It has the potential to be a valuable tool for risk stratification and clinical follow-up.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging