Volume 96  ·  Issue 19  ·  2016

translational medicine, or translational research, has been exactly 20 years since the concept of "translational medicine" was formally proposed by Lancet in 1996. Its main purpose is to promote the two-side way of basic medical research and clinical application: "from bench to bedside" refers to the validation of laboratory research results in humans, thus translating them into clinical practice; "from bedside to bench" It means that the scientific questions of clinical refinement are answered through basic research methods, thus deepening the understanding of the mechanisms behind clinical phenomena. It should be said that translational medicine builds a bridge between basic researchers and clinicians, refining scientific problems from clinical needs, finding solutions to problems through basic and clinical research, and ultimately improving the level of diagnosis, treatment and prevention^[1,2]。

The pituitary is the most complex and important endocrine organ of the human body. There are many pituitary diseases, including pituitary adenomas, craniopharyngiomas, pituitary cysts, etc. With the development of medical diagnostic technology and the improvement of people's health awareness, the detection rate of pituitary diseases has been increasing in recent years^[1]。 They can cause endocrine dysfunction, damage of adenopituitary-target gland axis, compression and invasion of surrounding important tissue structures, and seriously affect human health. The diagnosis and treatment of pituitary diseases in China began in the 1970s. With the development of modern neurosurgery, endocrinology, imaging and pathology, great progress has been made in the research of pituitary diseases. In 2015, the "Expert Consensus on Surgical Treatment of Pituitary Adenoma in China" was released, which played a positive role in promoting the standardized diagnosis and treatment of pituitary diseases in China^[2]。

To summarize the treatment outcome of surgery for male prolactinoma.

One hundred and eighty-four cases of male prolactinoma who underwent surgery were analyzed retrospectively.The average age of patients was 36.3 years, and the mean course was 41.9 months.The main clinical manifestation included sexual dysfunction (47.4%), headache (55.9%) and visual disturbance (46.7%). The serum prolactin levels ranged from 6.83 to 9 325.32 nmol/L.The size of tumors varied from 6 mm to 70 mm.Suprasellar adenoma with visual deficits accounted for 40.7%. 98.9% patients underwent pituitary adenoma resection via single nasal transsphenoidal approach.

Postoperative pathological Ki-67 index of most patients (45.1%) were less than 1%.After surgical therapy, 163 patients (88.6%) got relief of symptoms, 57 patients (31.0%) achieved initial remission, and 26 patients (45.6%) unfortunately recurred. The possibility of gross resection decreased as tumor size increased (P<0.05). Preoperative PRL had no significant relation with both tumor size and extent of resection (P>0.05). The favorable prognosis predictive factors included microadenoma, intrasellar adenoma and Ki-67 index≤3 (P<0.01).

Male prolactinomas is an invasive tumor with higher serum prolactin level.Tumor size could predict degree of gross resection while predictors for recurrence include tumor size, growth pattern and Ki-67 index.

To evaluate the quality of life (QoL) of patients with nonfunctioning pituitary adenoma (NFPA) after systematic treatment.

We searched all published articles involving in the QoL of patients with NFPA on line, and analyzed the results by the Revman5.3 software.

Five studies met the criteria of meta-analysis.The results of meta-analysis wereas follows: Physical function MD=0.76, 95%CI (-4.13, 5.64 ), P=0.76; Physical prole MD=-2.05, 95%CI (-7.41, 3.31), P=0.45; Body pain MD=3.50, 95%CI (1.11, 5.90), P=0.004; General health MD=-7.19, 95%CI (-12.77, -1.61), P=0.01; Vatility MD=-3.48, 95%CI (-7.39, 0.43), P=0.08; Social function MD=-4.64, 95%CI (-6.99, -2.38), P<0.000 1; Mental health MD=-0.05, 95%CI (-2.30, 2.20), P=0.96; Role emotion MD=-5.08, 95%CI (-8.20, -1.91), P=0.002.

This meta-analysisindicated thatthe QoL of patients with NFPA was damaged on the dimensions of general health, social function and role emotion.The dimension of physical painin patients with NFPA was better than that in general population, and there was no difference between other health dimensions.

To investigate the outcomes of the Endoscopic transsphenoidal surgery for patients with pituitary adenomas, analyze the learning curve and provide reference for future surgeries.

Retrospective analysis was carried out on 124 patients by endoscopic transsphenoidal surgery with a single neurosurgeon over a period spanning from January 2010 to January 2014 at Peking Union Medical College Hospital.The changes of endocrine and tumor imaging before and after surgery were analysed. Operative time and complication rates of one surgeon in the early period of learning curve were compared with that in later period.

There were significant differences in Gross total resection (GTR) rate of pituitary adenomas with different sizes and different Knosp classifications (P<0.01,P<0.01). GTR rate of huge adenomas was significantly lower than that of macroadenoma and adenomas (P<0.05). GTR rate of Knosp 4 grade adenoma was significantly lower than that of Knosp 0-3 level (P<0.05). No significant difference in GTR among all types of functional pituitary adenomas and hormone levels after surgery was observed (P>0.05). In addition, no significant difference (P>0.05) in complications among different sizes, Knosp grade and type of pituitary adenomas was observed.GTR of Knosp 4 adenoma in later period of the learning curve was significantly higher than that in early period (P<0.05). Meanwhile the operative time was significantly lower than early period (P<0.05).

Endoscopic transsphenoidal pituitary adenoma resection has the advantages of wider surgical field, higher GTR rate, less trauma, fewer complications and better life quality of patients.Through standardized learning, the GTR rate of the invasive pituitary adenomas can be improved.

To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations.

In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015.

As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study.

INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.

To evaluate the clinical efficacy of anterior debridement combined with posterior atlantoaxial fusion for atlantoaxial Tuberculosis.

From February 2005 to February 2013, 7 patients, 3 males and 4 females, with atlantoaxial Tuberculosis underwent anterior debridement combined with posterior atlantoaxial fusion in Department of Orthopedics Zhengzhou University People's Hospital were selected.In the preoperative and final follow-up, Japanese Orthopaedic Association score (JOA), neck disability index (NDI) and Frankel Classification were used to evaluate neurological function and calculate improvement rate.At final follow-up, clinical efficacy was evaluated by Odom's grade.Situation of internal fixation, fusion of upper cervical were assessed by X-ray, CT scan and MRI scan.

Bony fusion were achieved in 7 cases after operation in 12 months. Tuberculosis were reached clinical cure between 17 and 21 months. At follow The JOA score increased from (11.1±0.7) preoperatively to (15.3±0.5) in final follow-up(P<0.05), and the NDI decreased from (34.0±4.6) preoperatively to (10.1±1.3) in final follow-up (P<0.05). At last follow-up, according to Odom's standard, excellent were obtained in 5 cases, good 1 cases and ordinary 1 case. Frankel Classification of all cases improved from D class to E.

The treatment of anterior retropharyngeal debridement combine with atlantoaxial fusion, and local anti-tuberculosis drug using intraoperative, not only could obtain reliable clinical efficacy, completly removal of lesions, but also obtain strong stability, which plays an important role in the treatment of atlantoaxial Tuberculosis.

To evaluate the safety and efficacy of microwave ablation combined with curettage in the treatment of long bone metastases.

From April 2010 to June 2015, 38 patients with long bone metastases were adopted, who all underwent microwave ablation combined with curettage with 40 lesions involved in Department of Orthopaedic Oncology, Beijing Jishuitan Hospital. There were 22 males and 16 females with an average age of 58.3 years (range from 32 to 83 years). Solitary metastases were found in 9 cases and multiple metastases in 29 patients. Primary malignancies included: 15 cases of lung cancer, 7 cases of renal carcinoma, 4 cases of breast cancer, 3 cases of liver cancer, 1 case of thyroid carcinoma, 1 case of endometrial carcinoma, 1 case of cervical carcinoma, 1 case of esophageal carcinoma and 6 cases of carcinoma of unknown primary. The operative sites included the femur (n=21), the humerus (n=12) and the tibia (n=7). There were 23 cases of pathologic fractures which included: 12 in femur, 10 in humerus and 1 in tibia. Curettage after in situ microwave ablation was performed in 40 lesions. Reconstructions were carried out in all lesions: bone cement filling alone in 1 lesion and bone cement filling with metal implants in the other 39 lesions.

The mean follow-up was 6.9 months (range; 1-65 months). During the follow-up, 22 patients died and 16 patients were alive. The 6-month overall survival (OS) was 73.7%, and the 1-year and 2-year OS were 48.6% and 28.1% respectively. The postoperative survival time was 7.1 months on average (range 2-40 months) in the 22 patients who finally died. The occurrence of pathological fracture had a significant effect on the OS (χ²=5.606, P=0.018). The local recurrence rate was 10% (4/40), which occurred at 6.8 months after the operation on average (range 2-14 months). No complications occurred in the perioperative period, and there were no complications such as internal fixation failure or pathological fracture noticed during the follow-up period. The scores of VAS, KPS and ECOG were significantly improved after operation. The mean MSTS score was 22 points (range 17-28 points) in 33 evaluable locations and the rate of excellent and good was 72.7%.

Microwave ablation combined with curettage appears to be a safe and effective approach in the surgical treatment of long bone metastases, which can relieve local pain and control the local development of bone metastases.

To evaluate the relationship between renal corticomedullary differentiation, renal cortical thickness and age-related changes with non-contrast-enhanced steady-state free precession(SSFP) magnetic resonance imaging (MRI) and spatially selective inversion recovery(IR) pulse technology as well as its applied value .

A total of 76 healthy volunteers had been recruited from August 2014 to June 2015 in First Hospital of China Medical University.All volunteers were divided into three groups: 2-40 years old, 41-60 years old, 61-80 years old. All 76 volunteers underwent non-contrast-enhanced steady-state free precession(SSFP) 3.0 T MRI scan using variable inversion times (TIs)(TI=1 000, 1 100, 1 200, 1 300, 1 400, 1 500, 1 600, 1 700 ms). The renal corticomedullary differentiation was observed and the signal intensity of renal cortex and medulla were measured respectively as well in order to calculate renal corticomedullary contrast ratio. Besides, renal cortical thickness and renal size were measured.

All 76 volunteers were successfully performed all the sequences of MRI scan, including 152 useful imaging of kidney in total. The renal corticomedullary differentiation was clearly shown in all subjects. There was negative correlation between the optimal inversion time(TI) and age(r=-0.65, P<0.01). Similarly, negative correlation was observed between renal corticomedullary contrast ratio and age(r=-0.35, P<0.01). The mean renal cortical thickness of all subjects was (5.33±0.71)mm and there were statistically significant difference among those different groups, which was negative-related with age(r=-0.79, P<0.01). There was no statistically significant difference between sexuality and renal cortical thickness.Additionally, renal cortical thickness had no statistically significant difference in both sides of kidneys.

The renal corticomedullary differentiation is depicted clearly by means of non-contrast-enhanced steady-state free precession MRI with spatially selective inversion recovery pulse technology. The optimal inversion time decreases along with the increase of age. In the meanwhile, the renal cortical thickness could be measured truthfully and accurately.

To investigate the differential diagnostic value of DTI parameters in breast mass lesions by comparing apparent diffusion coefficient (ADC), fractional aniotropy (FA) and maximum eigenvalue (λ1)of normal glandular tissue, benign lesions and malignant lesions.

A total of 71 women patients with 74 mass lesions between December 2013 and October 2015 were enrolled from Beijing Chao-Yang Hospital.MRI protocol included dynamic contrast-enhanced MRI (DCE-MRI)and diffusion tentor imaging(DTI) were executed.The ADC, λ1 and FA of lesions and normal glandular tissue were calculated.The ADC, λ1 and FA of lesions were compared by paired t test between the benign/malignant tumors and the contratlateral healthy breast tissue.ROC curve analysis was performed to compare diagnostic performance based on the area under the curve(AUC). The sensitivity and specificity of the DCE-MRI combined with ADC and DCE-MRI combined with λ1 were calculated.

The ADC, FA and λ1 values of malignant lesions were (1.09±0.18)×10 ^-3 mm²/s, 0.22±0.02 and(0.97±0.19)×10^-3 mm²/s , these values of benign lesions were (1.52±0.19)×10^-3 mm²/s, 0.21±0.02 and(1.79±0.19)×10^-3 mm²/s, there were statistically significant differences (all P<0.05). Area under the curve of ADC, FA and λ1 were 0.990, 0.605 and 0.978, respectively. The AUC of FA was lower than that of ADC and λ1(P<0.01, <0.01), but there was no difference between the AUC of ADC and that of λ1(P=0.131 6). The sensitivity DCE-MRI combined with ADC and DCE-MRI combined with λ1 was 88.6% vs 97.1%( P=0.353 3), the specificity was 84.6% vs 97.4%(P=0.113 0).

ADC and λ1 is helpful to differentiate malignant from benign in mass lesions.

To investigate the real-time tissue elastography and 3D contrast-enhanced ultrasonography(CEUS) in breast lumps differential diagnostic value.

A total of 126 patients (180 lumps) with breast mass were retrospectively analyzed from December 2012 to December 2014 in Tumor Hospital Affiliated To Xinjiang Medical University.All patients were divided into three groups by using stratified random method.Each group was detected by real-time tissue elastography, 3D CEUS and two joint inspection.Each group of 42 cases (60 lumps) was confirmed by the pathological results as gold standard.Diagnostic sensitivity, specificity and coincidence rate of different methods were compared.

The benign masses of ultrasound contrast showed the punctate, linear and nodular enhancement, and the border of enhancement was smooth.The malignant tumors were mainly dominated by uneven and high enhancement. There was no statistical difference in sensitivity, specificity and coincidence rate between elastography group and 3D CEUS group (64.7% vs 73.5%, 69.2% vs 76.9%, 66.7% vs 75.0%, all P>0.05). The sensitivity, specificity and coincidence rate of two joint inspection group were higher than those of elastography group and 3D CEUS group, the differences were statistically significant (97.1%, 92.3% and 98.3% , allP<0.05).

3D CEUS combined with real-time tissue elastography is of high value in the diagnosis of breast masses.

To investigate the value of deceleration capacity of rate (DC) and heart rate deceleration runs(DRs) in predicting cardiovascular events in patient with acute myocardial infarction (AMI).

This study included 166 patients with AMI, who underwent ECG with sinus rhythm.These patients were followed-up for major adverse cardiac events (MACE). The receiver operating characteristic curve (ROC) was drawn to determine the best values for estimating the MACE.

The mean follow-up time was (20.5±2.8) months, with 13 cases of cardiac death.There was statistically significant difference of DC, DRs and standard diviation of NN intervals(SDNN-24) between the death group and survival group.The area under the curve (AUC) of DC, DR4 and DR8 were larger than SDNN-24 (0.874, 0.804 vs 0.727). The values of DC, DR2, DR4 and root mean square of the successive differences(RMSSD) in the group of patients who underwent cardiac adverse events were smaller than the group of patients who didn't, and the AUC of DC was slightly higher than that of RMSSD.

DC and DRs have important predictive value for cardiac death and MACE and can screen high-risk patients in patients with AMI.

To analysis the clinical features of cardiovascular involvement in Behcet's disease.

We reviewed 35 medical records of Behcet's disease with cardiovascular lesions in Anzhen Hospital, Capital Medical University from January 2002 to January 2014. 77.1% patients (27/35) were male. The mean (±s) age when cardiovascular diseases occur was 37.19±10.4 years in male and 36.0±8.6 years in female respectively.

The clinical spectrum of cardiovascular abnormalities included valvular regurgitation (20, 57.1%), conduction system disturbances (10, 28.6%), intracardiac thrombosis(1, 2.9%), aneurysms of the arteries (13, 37.1%), artery stenosis or occlusion (5, 14.3%), pulmonary vascular diseases(3, 8.6%), venous thrombosis(4, 11.4%). Twenty patients had more than one of these lesions. Inflammatory indicators had no significantly difference between the above subgroups (P>0.05). Treatments included corticosteroids and immunosuppressive drugs, together with symptomatic treatments, intervention therapy and operation.Two inpatient died from multiple organ dysfunction syndrome and cardiac shock respectively.

Cardiovascular involvement is a remarkable systemic lesion of Behcet's disease. Multi-subject cooperation is beneficial for the diagnosis and treatment of the disease.

To evaluate the diagnosis value of photoplethysmography (PPG)-based device for detecting obstructive sleep apnea syndrome.

Patients who visited sleep medicine center in West China hospital from March 2014 to March 2015 with a main complain of snoring were selected into this study, and they were simultaneously monitored with the PPG-based device while undergoing polysomnography (PSG). Using PSG as"gold standard", the sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) as well as corresponding areas under the receiver operator curves for an apnea hypopnea index (AHI) ≥5/h, ≥15/h and ≥30/h were calculated for PPG.

Valid results were available for 93 subjects, among them there were 64 men and 29 women with a mean age of (44±13) years old.There were no significant difference between total sleep time, wake time after sleep onset, AHI and oxygen saturation derived by PPG and PSG.Positive correlation was found between PPG-derived and PSG-derived AHI (r=0.945). For AHI≥5/h, ≥15/h and ≥30/h respectively according PSG, sensitivity was 93%, 88%, 92%, specificity was 79%, 93%, 95%, PPV was 95%, 97%, 96%, NPV 75%, 76%, 91% for PPG. The corresponding areas under the receiver operator characteristic curves were 0.981, 0.996 and 0.995 respectively.

PPG-derived data is consistent with simultaneous in-lab PSG in the diagnosis of obstructive sleep apnea syndrome.

To investigate the positive effects of mouse nerve growth factor(mNGF) on cognitive impairment in whole brain irradiation rats.

Fifty-five male Sprague-Dawley rats were randomly divided into normal control group, mNGF treated group, saline treated group.mNGF treated group and saline treated group were cranial irradiated at a single dose of 12 Gy by X-ray.30 days after radiation each group were treated with correspondent drugs.60 days after radiation, Morris water maze experiment, EB leakage of the brain, and expressions of neuN, vWF, ZO-1 in hippocampus by immunofluorescence, and expressions of neuN, vWF, ZO-1, VEGF and GFAP in hippocampus by Western blot were tested and analyzed.

The escape latencies: normal control group< mNGF treated group< saline treated group; the numbers of crossing hidden platform in these 3 groups were 3.00± 1.08, 1.50± 1.08, 0.38± 0.48 times (P<0.01). EB leakage of these 3 groups were 0.14±0.14, 0.66±0.20 and 1.36±0.27 μg/g (P<0.05). In immunofluorescence, expressions of neuN, vWF and ZO-1: normal control group> mNGF treated group> saline treated group.In Western blot, expressions of neuN, vWF and ZO-1: normal control group> mNGF treated group> saline treated group, yet the expressions of VEGF and GFAP: normal control group< mNGF treated group< saline treated group.

mNGF ameliorates cognitive impairment after whole brain irradiation.

To explore the influence of patatin-like phospholipase domain-containing protein 3 (PNPLA3) on palmitic acid (PA)-induced hepatocyte apoptosis and its mechanism.

Human hepatocarcinoma cell line HepG2 cells were transfected with PNPLA3^WT-pcDNA3.1 (PNPLA3^WT group) and PNPLA3^I148M-pcDNA3.1 (PNPLA3^I148M group) plasmids respectively to overexpress wild type or mutant type PNPLA3, and cells transfected with empty vector pcDNA3.1 (NC group) were set as control group.After 24 h PA incubation, Oil red staining was used to determine lipid deposition, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) was used to measure apoptosis.Western blot was used to detect the protein level of endoplasmic reticulum (ER) stress and associated apoptosis.Enzyme-linked immunosorbent assay (ELISA) was used to test lysolecithin (LPC) levels in the cellular supernatant.

After 24 h PA incubation, there was no significant difference in lipid deposition among three groups.Compared to NC group, the cell apoptosis rates of PNPLA3^WT and PNPLA3^I148M groups were increased by 2 times and 3 times respectively.The levels of ER stress PRKR-like endoplasmic reticulum kinase (PERK) pathway associated proteins, immunoglobulin-binding protein (BIP), p-PERK, p-eIF2α, and ER stress associated apoptosis pathway proteins, CCAAT/enhancer binding homologous protein (CHOP), p53 upregulated modulator of apoptosis (PUMA), Bax, caspase-3 were higher, and were more significant in PNPLA3^I148M group.The LPC level in the supernatant of PNPLA3^WT and PNPLA3^I148M groups were about 5 times and 1.5 times of NC group respectively after PA incubation.

PNPLA3 may be involved in palmitic acid-induced apoptosis mediated by hepatocyte ER stress through regulating LPC metabolism.

Case 1, 12 years old, underwent radical resection for tetralogy of Fallot in an external hospital 6 years ago. Postoperative review revealed residual ventricular septal shunt. Six months ago, the patient developed active chest tightness and shortness of breath, without cyanosis and dyspnea. In August 2015, he went to the People's Hospital of Zhengzhou University and was admitted to the Children's Heart Center with the diagnosis of "6 years of residual leakage of ventricular defect after radical resection of tetralogy of Fallot". Physical examination: heart rate 78 beats/min, peripheral blood oxygen saturation 98%, blood pressure 100/60 mmHg (1 mmHg =0.133 kPa), body weight 40 kg, height 160 cm, coarse breathing sounds in both lungs, no dry and wet rales, no bulge in the precordial area, no obvious enlargement of the heart turbidity boundary, uniform heart rhythm, grade III/6 systolic murmur can be heard in the 3rd to 4th intercostal area on the left margin of sternum, and P2 is not hyperactive. Echocardiography of the admitted heart showed that a strong patch-like echo of the interventricular septum was visible at 11 o'clock in the short axis section of the great artery, and the position was fixed. The residual shunt beam width was about 6 mm above the patch, and the stump was about 4 mm away from the right coronary valve root of the aorta. The blood flow in the right ventricular outflow tract was unobstructed, the suprapulmonary valve flow velocity was 2.62 m/s, the pulmonary valve was moderate regurgitation, the tricuspid valve was mild regurgitation, the right heart was large, and the inner diameter of the rest of the cardiac chambers and large blood vessels was normal. Ultrasound impression: consistent with changes after radical resection of tetralogy of Fallot, residual shunt at ventricular level (left to right), pulmonary regurgitation (moderate), tricuspid regurgitation (mild), and right heart enlargement. Thoracic orthographic radiograph showed postoperative changes of tetralogy of Fallot, and the cardiothoracic ratio was 0.53. Admission electrocardiogram showed sinus rhythm, incomplete right bundle branch block, right deviation of QRS axis. Laboratory tests: No obvious abnormalities were found in blood routine, urine routine, coagulation analysis and biochemical analysis. Based on the above clinical data, it was clearly diagnosed as "residual ventricular septal leakage after radical resection of tetralogy of Fallot". The patient and his family refused reoperation and interventional occlusion under radiation, and finally decided to perform ultrasound-guided percutaneous residual ventricular septal occlusion.

The Encyclopedia of DNA Elements (ENCODE) study indicates that nucleotides in the human autosomal genome are essentially transcribed, and confirms that 80% of the genome has specific biological functions^[1]。 Among them, less than 3% of the transcripts are from genes encoding proteins, and the remaining non-coding transcripts may affect gene expression through different mechanisms. According to their length, non-coding RNAs can be divided into long-chain non-coding RNAs (lncRNAs,>200 nt) and short-chain non-coding RNAs (≤200 nt)^[2]The latter include microRNAs (miRNAs), RNAs that interact with Piwi proteins (piRNAs), and small interfering RNAs (siRNAs). Exosomes are vesicles secreted by cells with double lipid membranes, which can achieve horizontal transfer of proteins, mRNA, miRNA and lncRNA by fusion with target cells. The study on the role of lncRNA in exosomes in diseases is just beginning, and the research on the role of lncRNA in exosomes in diseases is reviewedTable 1)。

Rejection is the basic function of the immune system to maintain homeostasis of the internal and external environment of the body. Immune response plays an important role in inhibiting the growth and invasion of bone metastases. In the skeletal microenvironment of bone metastases, tumor cells can stimulate osteoclastogenesis and enhance osteolytic activity of osteoclasts. Osteolysis releases growth factors stored in the bone, which in turn further promote tumor growth and secretion of related factors in the bone. A vicious circle of bone destruction forms between tumor cells and osteoclasts. According to the regulatory effects on bone metastasis, immune cells are divided into three categories: anti-bone metastasis immune cells, pro-bone metastasis immune cells and dual regulatory immune cells. Immune cells are involved in regulating the vicious cycle of bone metastases. Immune cell function may be altered under different conditions, or even completely opposite.

Dopamine receptor agonist (DA), as a first-line treatment for prolactin (PRL) adenoma, can effectively reduce PRL levels and reduce tumor volume, thereby improving neurological dysfunction caused by space occupation, and restoring gonadal function^[1,2]。 Previous studies have reported that DA can restore prolactin levels to normal in 85% to 90% of patients with prolactin adenoma, and reduce the tumor bodies in 80% of prolactin macroadenomas^[3]。 Currently, DA includes cabergoline, bromocriptine, quigolide, dihydroergoline, ergoethylurea and methergoline, with cabergoline and bromocriptine being the most commonly used. Bromocriptine as the first DA introduced into clinical practice^[4]Has a relatively short elimination half-life, therefore, doses ranging from 2.5 to 15 mg 2 or 3 times a day, and 18% to 25% of patients show bromocriptine resistance^[5,6]。 Compared with other DA, cabergoline has better efficacy and fewer adverse effects^[1,7]。 Because cabergoline has a plasma half-life of approximately 65 h, it should only be taken once or twice a week, which greatly improves patient compliance^[8]。 However, cabergoline and bromocriptine have a common disadvantage, that is, they need to be taken for a long time or even lifetime, and blind withdrawal of the drug can easily lead to the rebound of hyperprolactinemia and tumor regeneration^[9,10,11]。 If prolactin levels remain normal for at least 2 years and the tumor size shrinks by more than 50%, the DA dose can be gradually reduced, as low-dose drug therapy maintains stable prolactin levels and tumor size at this stage^[12]。 Therefore, how to reasonably reduce or even stop the drug is a very important clinical topic. In this paper, the discontinuation strategy of prolactin adenoma after DA treatment was reviewed, hoping to be useful for clinical reference.