Refractory prolactinoma is the most common pituitary neuroendocrine tumor.Dopamine receptor agonists(DA)are the primary choice for drug treatment.Most patients with prolactinomas respond well to DA.However,a minority of prolactinomas patients still show resistance to DA.Although drug-resistant and refractory prolactinomas are rare in clinical practice,their treatment is extremely challenging.Even a combination of drug therapy,multiple surgeries,and radiotherapy may not yield satisfactory outcomes.Therefore,standardizing the diagnosis and treatment process and pathway for refractory prolactionmas and exploring more effective multidisciplinary collaborative treatment strategies are urgent problems to be solved.In the clinical management of refractory prolactinomas,it is often necessary to consider the patient's condition comprehensively,replace other types of DA,or consider surgery,radiotherapy,and immunotherapy,which requires multidisciplinary diagnosis and treatment.This review synthesizes the latest literature at home and abroad to systematically discuss the latest advances in drug therapy,surgery,and radiotherapy treatments for refractory prolactionmas,aiming to provide new ideas for basic research,clinical diagnosis and treatment.

Objective:To explore the mechanism of herb-partitioned moxibustion in relieving rat intestinal inflammation by focusing on the neutrophil extracellular traps(NETs)in Crohn disease(CD)development. Methods:Rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion group,and a mesalazine group.The CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid except for rats in the normal group.Rats in the normal group and model group did not receive any treatment but had the same fixation as the other groups.Rats in the herb-partitioned moxibustion group received herb-partitioned moxibustion at Qihai(CV6)and bilateral Tianshu(ST25).Rats in the mesalazine group received intragastric administration of mesalazine enteric-coated tablets.The general situation of rats in each group was recorded,and the histopathological changes in the colon were observed and scored by hematoxylin-eosin staining.The serum concentrations of NETs DNA(NETs-DNA),neutrophil elastase(NE)-DNA,and myeloperoxidase(MPO)-DNA were detected by ABC enzyme-linked immunosorbent assay,and the citrullinated histone 3(citH3),MPO,and NE protein and mRNA expression levels in rat colon tissue were observed by immunofluorescence and real-time quantitative polymerase chain reaction. Results:Compared with the normal group,the mucosal ulcer reached the muscularis,the epithelium was incomplete,the goblet cells decreased obviously with significant inflammatory cell infiltration in the colon;the colonic mucosa damage index(CMDI)score increased significantly(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations increased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue increased significantly in the model group(P<0.01 or P<0.05).Compared with the model group,the mucosal epithelium in the herb-partitioned moxibustion group and the mesalazine group was repaired and the goblet cells increased with a few infiltrating inflammatory cells in the colon;the CMDI score decreased(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations decreased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue was down-regulated(P<0.01 or P<0.05). Conclusion:Herb-partitioned moxibustion reduced the serum NETs complex and inhibited the protein and mRNA expression of NETs complex in the colon tissue,which may be one mechanism of herb-partitioned moxibustion in relieving colon mucosal inflammation in CD.

Humans ; Female ; Deep Learning ; Ovarian Neoplasms/genetics* ; Carcinoma, Ovarian Epithelial/genetics* ; Neural Networks, Computer ; RNA

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

OBJECTIVE: To analyze the difference in clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under Quadrant channel system combined with microscope and percutaneous pedicle screw in the treatment of degenerative lumbar spondylolisthesis. METHODS: A total of 114 patients with single-segment degenerative lumbar spondylolisthesis from June 2015 to February 2019, were divided into three groups according to the surgical methods, such as the MIS-TLIF under the microscope surgery group ( microscope group), MIS-TLIF combined with percutaneous pedicle screw technique surgery group(percutaneous group) and posterior lumbar interbody fusion surgery group (open group). In the microscope group, there were 12 males and 26 females, aged from 42 to 83 years with an average of (63.29±9.09) years. In the percutaneous group, there were 16 males and 22 females, aged from 45 to 82 years with an average of (63.37±7.50) years. In the open group, there were 12 males and 26 females, aged from 51 to 82 years with an average of (63.76±8.21) years. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage, length of surgical incision, frequency of intraoperative fluoroscopy and postoperative time of lying in bed were recorded to analyze the differences in surgical related indicators. Visual analogue scale (VAS) of waist and leg pain in preoperative and postoperative period (3 days, 3 months, 6 months and 12 months) were recorded to evaluate pain remission;Oswestry Disability Index(ODI), Japanese Orthopaedic Association (JOA) score were recorded to evaluate the recovery of waist and leg function on preoperative and postoperative 12 months. The lumbar spondylolisthesis rate and intervertebral height at 12 months after operation were recorded to evaluate the reduction of spondylolisthesis. The Siepe intervertebral fusion standard was used to analyze the intervertebral fusion rate at 12 months after operation. RESULTS: ①All 114 patients were followed up more than 1 year, and no complications related to incision infection occurred. In the microscope group, there was 1 case of subcutaneous effusion 8 days after operation. After percutaneous puncture and drainage, waist compression, and then the healing was delayed. In the percutaneous group, 2 cases of paravertebral muscle necrosis occurred on the side of decompression, and the healing was delayed after debridement. In open group, there was 1 case of intraoperative dural tear, which was packed with free adipose tissue during the operation. There was no postoperative cerebrospinal fluid leakage and other related complications.① Compared with microscope group, percutaneous group increased in operation time, intraoperative blood loss, postoperative wound drainage, surgical incision length, intraoperative fluoroscopy times, and postoperative bed rest time. In open group, intraoperative blood loss, postoperative wound drainage, surgical incision length, and postoperative bed rest time increased, but the intraoperative fluoroscopy time decreased. Compared with percutaneous group, the intraoperative blood loss, wound drainage, surgical incision length, and postoperative bed rest time in open group increased, but operative time and the intraoperative fluoroscopy time decreased(P<0.05). ②ODI and JOA scores of the three groups at 12 months after operation were improved compared with those before operation (P<0.05), but there was no significant difference between the three group(P>0.05). ③Compared with microscope group, the VAS of low back pain in percutaneous group increased at 3 days after operation, and VAS of low back pain in open group increased at 3 days, and 12 month after operation. Compared with percutaneous group, the VAS low back pain score of the open group increased at 3 months after operation (P<0.05). ④ The lumbar spondylolisthesis rate of the three groups of patients at 12 months afrer operation was decreased compared with that before operation(P<0.05), and the intervertebral heigh was increased compared with that before operation(P<0.05), however, there was no significant difference among three groups at 12 months afrer operation(P>0.05). ⑤ There was no significant difference between three groups in the lumbar fusion rate at 12 months afrer operation(P>0.05). CONCLUSION The MIS-TLIF assisted by microscope and the MIS-TLIF combined with percutaneous pedicle screw are safe and effective to treat the degenerative lumbar spondylolisthesis with single-segment, and the MIS-TLIF assisted by microscope may be more invasive, cause less blood loss and achieve better clinical efficacy.
Blood Loss, Surgical ; Case-Control Studies ; Female ; Humans ; Low Back Pain ; Lumbar Vertebrae/surgery* ; Male ; Minimally Invasive Surgical Procedures/methods* ; Postoperative Hemorrhage ; Retrospective Studies ; Spinal Fusion/methods* ; Spondylolisthesis/surgery* ; Surgical Wound ; Treatment Outcome

Objective:To explore the effect and mechanism of Guizhitang with different proportions of Cinnamomi Ramulus and Paeoniae Alba Radix on overactive cardiac sympathetic nerves in salt-sensitive hypertensive rats. Method:Randomly divide the forty male 6-week-old salt-sensitive hypertensive rats into five groups： the normal control group， the model group， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶2 group，and the Cinnamomi Ramulus and Paeoniae Alba Radix 2∶1 group， each group has 8 animals， the normal control group was fed with low-salt feed， and the remaining four groups were fed with 8% high-salt feed. After 4 weeks of feeding， gastric feeding was started. Give both the normal control group and model group saline and the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group， the 1∶2 group，and the 2∶1 group， were given Guizhitang aqueous solution at 4.0， 5.5 and 5.5 g·kg^-1， respectively. Continuous gavage intervention was held for 4 weeks. IITC multi-channel non-invasive sphygmomanometer was used to detect changes of systolic blood pressure before and after treatment in rats. Left ventricular anterior wall end-diastolic thickness （LVAWd） and interventricular septal diastolic thickness （IVSd） were detected by echocardiography. Hematoxylin-eosin（HE）staining and Masson staining were used to observe the myocardial morphological changes of rats in each group， Western blot was used to detect the expression of nerve growth factor （NGF）， growth-associated protein 43 （GAP43） and tyrosine hydroxylase （TH） protein. Result:After 4 weeks of intervention with Guizhitang， compared with the normal control group， the blood pressure， LVAWd and IVSd of the model group were significantly increased， and the expressions of NGF， TH and GAP43 protein were significantly increased （P<0.01）. HE and Masson staining results showed that the model group had myocardial cell edema， a large number of inflammatory cell infiltration， myocardial fiber hyperplasia and disordered arrangement， and a large amount of collagen deposition could be seen in the intercellular substance. Compared with model group， the systolic blood pressure of rats in each Guizhitang group increased slowly， and the expression of NGF， TH and GAP43 protein decreased （P<0.05，P<0.01），the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group has the best effect. The results of echocardiography shows that the 1∶1 Guishao group could reduce LVAWd and IVSd levels （P<0.05，P<0.01）， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶2 group could reduce IVSd level （P<0.05）， there was no statistical difference in LVAWd， there was no statistical difference in LVAWd and IVSd in 2∶1 group. In terms of myocardial morphology， each group of Guizhitang can reduce cell edema and inflammatory cell infiltration， reduce myocardial fiber hyperplasia and collagen deposition， and improve the disorder of myocardial fiber arrangement. Among them， the 1∶1 group has the best effect. Conclusion:Guizhitang can inhibit the overactive activation of cardiac sympathetic nervous system，reduce the extent of myocardial fibrosis， inflammatory infiltration and myocardial hypertrophy， and protect salt-sensitive hypertension rats， whose mechanism may be related to regulating the expression of heart NGF.Among them， the Cinnamomi Ramulus and Paeoniae Alba Radix 1∶1 group is better than the 1∶2 and 2∶1 group in reducing myocardial fibrosis， inflammatory infiltration and myocardial hypertrophy.