Volume 98  ·  Issue 09  ·  2018

The 2017 edition of the World Health Organization (WHO) pituitary tumor classification has been released recently^[1]Understanding the evolution of pituitary tumor classification will not only help clinicians to make a clear diagnosis and treatment of pituitary tumors, but also help them to conduct more in-depth translational research and further targeted therapy^[2]。 With the deepening of genomics, transcriptomics and metabolomics, people's understanding of pituitary tumors has been further deepened. The significance and implications of the 2017 version of WHO pituitary tumor classification are now reviewed as follows.

The 4th edition of the 2017 World Health Organization (WHO) new classification of endocrine organ tumors (hereinafter referred to as the new classification) has been published^[1]The changes from histopathology to molecular genetics of pituitary tumors have updated people's understanding, especially in the future clinical and scientific research work, it is necessary to combine a new classification system to standardize the diagnosis and treatment of pituitary tumors. Combined with the new classification, this article focuses on the classification of anterior pituitary tumors, and talks about the enlightenment and confusion brought to us by the new classification.

The release of the 2017 edition of the World Health Organization (WHO) Classification of Endocrine Tumors (hereinafter referred to as the new edition) has attracted wide attention from scholars from all walks of life^[1]。 The new version of the Endocrine Tumor Tissue Classification provides a subversive new definition of the classification of neuroendocrine tumors derived from the anterior pituitary gland.

The latest edition of the World Health Organization (WHO) Classification of Endocrine System Tumors (2017 Edition) was recently released. Some major changes have taken place in the classification of pituitary neuroendocrine tumors in the new edition. The main changes in the classification of pituitary endocrine tumors in the new edition focus on the following aspects^[1,2]: (1) the term "atypical pituitary adenoma" was removed; (2) introduction of a new tumor entity, "pituitary blastoma"; (3) The naming of pituitary adenoma has changed: it is no longer named after the type of secreted hormone, but after the differentiation lineage of tumor cells that make up the adenoma. For example, the naming of growth hormone adenoma is abolished and growth hormone cell adenoma is used to name; (4) Redefining some old solid tumors, such as zero cell adenomas, according to transcription factor expression; (5) highlighting five "high-risk pituitary adenomas", including sparse granular growth hormone cell adenomas, multi-hormone pituitary-specific Pou-homologous domain transcription factor (PIT-1) positive adenomas (previously known as quiescent third subtype adenomas), quiescent corticotropin cell adenomas, Crooke cell adenomas, and male prolactin cell adenomas; (6) The relationship between transcription factors and pituitary adenomas is pointed out, so that the classification of pituitary adenomas no longer relies on ultrastructural analysis; (7) It is strongly recommended to comprehensively assess whether adenomas are aggressive by evaluating clinical imaging parameters such as tumor proliferative potential (counting mitotic images and Ki-67 index) and invasion of surrounding tissues.

The 4th edition of the World Health Organization (WHO) Classification of Endocrine Organ Tumors was released in 2017^[1]In which a new description of the classification of pituitary tumors is given, seeTable 1Compared with the 3rd edition of the WHO classification in 2004^[2]。

This study aimed to analyze the application of cortical and subcortical stimulation threshold in identifying the motor pathway and guiding the resection of gliomas in the functional area, and to illustrate the minimal safe threshold by ROC method.

Fifty-seven patients with gliomas in the functional areas were enrolled in the study at Beijing Tiantan Hospital from 2015 to 2017. Anesthesia was maintained intravenously with propofol 10% and remifentanil. Throughout the resection process, cortical or subcortical stimulation threshold was determined along tumor border using monopolar or bipolar electrodes. The motor pathway was identified and protected from resection according to the stimulation threshold and transcranial MEPs. Minimal threshold in each case was recorded.

Total resection was achieved in 32 cases(56.1%), sub-total resection in 22 cases(38.6%), and partial resection in 3 cases(5.3%). Pre-operative motor disability was found in 9 cases. Compared with pre-operative motor scores, 19 exhibited impaired motor functions on day 1 after surgery, 5 had quick recovery by day 7 after surgery, and 7 had late recovery by 3 months after surgery. At 3 months, 7 still had impaired motor function. The frequency of intraoperative seizure was 1.8%(1/57). No other side effect was found during electronic monitoring in the operation. The ROC curve revealed that the minimal safe monopolar subcortical threshold was 5.70 mA for strength deterioration on day 1 and day 7 after surgery. Univariate analysis revealed that decreased transcranial MEPs and minimal subcortical threshold ≤5.7 mA were correlated with postoperative strength deterioration.

Cortical and subcortical stimulation threshold has its merit in identifying the motor pathway and guiding the resection for tumors within the functional areas. 5.7 mA can be used as the minimal safe threshold to protect the motor pathway from injury.

To evaluate the efficacy and safety of microsurgical in the treatment of temporal lobe cerebral cavernous malformation (CCM) with epilepsy.

Temporal lobe CCM patients with epilepsy admitted to our department were collected from January 2010 to September 2016. Locations of the CCM were divided into (1) lateral-lateral to the collateral sulcus; (2) mesial-mesial to the collateral sulcus. In the lateral group, patients were underwent intraoperative electrocorticography (ECoG)-guided resection of lesion and hemosiderin rim. In the medial group, a complete resection of the epileptogenic zone was performed in anterior temporal lobe and hippocampus and (or) amygdala according to lesion and hemosiderin rim. The follow-up period in all patients was at least 1 year. The outcome of epilepsy treatment was evaluated according to the standard Engel scale.

Eight patients belong to the lateral group, including 2 males and 6 females, mean age at epilepsy surgery was 35 years old, 100% of patients achieved Engel class Ⅰ the last follow up. The mesial group had 7 patients, including 4 males and 3 females, mean age at epilepsy surgery was 52 years old, 71.8% of the patients were Engel Class Ⅰ, 14% were Class Ⅱ, and 14% were Class Ⅲ. The patient who was Engel Class Ⅲ had a posterior temporal venous infarction due to injured the developmental venous anomalies (DVAs).

CCM Patients with epilepsy could benefit greatly from complete resection of hemosiderin rim and lesion. The epilepsy prognosis were closely correlated with the location of CCM. Further research is necessary to determine therapeutic strategies of CCMs with associated DVAs.

To explore the change and value of platelet aggregability(PA)in patients with subcortical ischemic vascular disease (SIVD).

A total of 108 patients with SIVD hospitalized in the Department of Neurology of the First Affiliated Hospital of Anhui Medical University from October 2015 to July 2017 were enrolled as SIVD group and 30 healthy cases were also in cluded as normal controlgroup (NC). According to magnetic resonance imaging(MRI), the SIVD group was further divided into two subtypes: lacunar infarction(LI) (n=31)and leukoaraiosis(LA) (n=77). The severity of LA was further graded according to the Fazekas scale. The maximum aggregation rate of platelets was measured by optical turbidimetry, respectively, using four arachidonic acid (ACA), two adenosine monophosphate (ADP) and collagen (COLL) as inducerin all subjects. The change of PA between the subtypes of SIVD and NC were compared, and the relationship between PA and the severity of LA was analyzed.

The level of PA in SIVD was significantly higher than those in NC (P<0.001). In comparison with NC, the level of PA was significantly higher in both LI and LA subgroups(P<0.05). Meanwhile, there was no significant difference between LA group and LI group (P>0.05). Moreover, between LA groups, the PA induced by COLL were significantly different between the LA3 group and the LA1 group (P=0.026). Correlation analysis showed that ageand the level of PA induced by COLL was positively correlated with LA grade (r=0.382, P=0.001; r=0.260, P=0.026). Multivariate logistic regression analysis revealed that after controlling for various factors, when induced by ACA, the risk of SIVD in the highest group (>86.80%) and higher group (82.63%-86.80%) was 13.95 and 3.09 times respectively higher than in the normal group(<82.63%), the differences were statistically significant (P<0.001,P=0.038); when induced by ADP, the risk of SIVD in the highest group (>87.63%) and higher group (82.80%-87.63%) was 20.78 and 5.85 times respectively higher than in the normal group (<82.80%), the differences were statistically significant (P<0.001,P=0.003); When induced by COLL, the risk of SIVD in the highest group (>87.60%) and higher group (83.80%-87.60%)was 28.53 and 9.02 times respectively higher than in the normal group (<83.80%), the differences were statistically significant (P<0.001,P=0.002).

The increasedlevel of PA is an independent risk factor of SIVD and closely related with the severity of LA .This study provides a theoretical basis for further understanding of the SIVD′s pathogenesis and for the prevention and treatment of SIVD in the clinical practice.

To evaluate the clinical characteristics and the corresponding MRI and laboratory findings in patients with neuromyelitis optica spectrum disorder (NMOSD) associated with area postrema (AP).

The study was a retrospective analysis of data from 120 NMOSD patients, and 18 cases were with AP out of these patients, The clinical presentation, MRI changes, serological markers and treatment outcome were reported.

AP occurred in 18 patients (15%, 18/120). AP was the onset symptom in 14 (14/18) patients and 3 days to 7 months (median 40 days) later, optic neuritis or myelitis was involved. One patient presented AP after optic neuritis. Three patients (3/18) had AP and myelitis or optic neuritis simultaneously. AP symptom presented as intractable nausea and vomiting, hiccups. Compared to the patients without AP (n=102), the patients with AP (n=18) had shorter duration and fewer numbers of optic neuritis(P<0.05). There was no statistical difference in sex, onset age, course of disease (relapsing or monophasic) and EDSS scores (P>0.05). The MRI revealed flake or linear lesions in medulla. Twelve patients had cervical cord lesions extending to medulla lesions (12/18). Eleven patients had long cord lesions extending more than 3 spinal cords. The AQP4-antibody did not differ in patients with or without AP (14/18 vs 75/102). The symptom of AP was successfully relieved with methylprednisolone.

AP symptoms/signs are common in patients with NMOSD. Vomiting and hiccups can be the first symptoms. The medulla lesions and the lesions extending to upper cervical cord are unique to NMOSD. Awareness of AP presentations is helpful for early diagnosis and proper treatment to prevent further disability.

To investigate the clinical characteristics and pharmaceutical therapy of elderly patients with chronic heart failure (CHF).

Using the multi-center retrospective cross-sectional survey, we analyzed 1 799 hospitalized patients with CHF as the main cause and NYHA heart function classification Ⅱ-Ⅳ from nine tertiary hospitals of Tianjin during March 2014 to February 2016. According to age, we divided them into non- elderly group(age<65 years), normal elderly group (age ≥65-79 years), and the old elderly group(age≥80 years). We analyzed the clinical characteristics and pharmaceutical therapy of different age groups of CHF patients.

One thousand seven hundred and ninety-nine patients with CHF, mean age (70±13) years old. Elderly patients over 65 accounted for 69.87%; men accounted for 61.53%; the average hospitalization days were 11.33 days, hospitalization days of the old elderly group were significantly prolonged to 13.26 days(P<0.05). With increasing age, the proportion of men, NYHA Ⅱ and HFrEF patients gradually decreased, the proportion of women, NYHA Ⅳ and HFpEF patients gradually increased(allP<0.05). The distribution of HFmrEF in different age groups was not statistically significant(P>0.05), accounting for one third. Etiology and comorbidities: the first eight diseases were coronary heart disease, hypertension, hyperlipidemia, diabetes, pulmonary infection, cerebrovascular disease, renal dysfunction and atrial fibrillation. The ratios of old elderly group with pulmonary infection, cerebrovascular disease, renal dysfunction and atrial fibrillation were significantly higher than the non-elderly group( allP<0.05). The numbers of comorbidity in old elderly group and the normal elderly group were higher than the non-elderly group, respectively 3.74, 3.37 and 2.82(allP<0.05). The application rate of β-blockers and ACEIs in non-elderly group was higher than the other groups (P<0.05). The application rate of ARBs, digitalis, energy metabolites and nitrates in the normal elderly group and the old elderly age group was higher than the non-elderly group (P<0.05).

With increasing age, the proportion of men and HFrEF patients with CHF gradually decrease, the proportion of women and HFpEF patients with CHF gradually increase, the proportion of old elderly men and women tend to be equal, HFmrEF maintains the proportion of about 1/3, no change with age. The elderly patients with CHF have more comorbidity, worse heart function, and more serious heart failure.The overall application of anti-HF drugs in elderly CHF patients needs to be improved.

To compare the acute hemodynamic effects of intravenous fasudil with different dosage on patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH).

Sixty patients (37±17 years old) with CHD and PAH were consecutively enrolled. All patients underwent heart catheterization. The patients were randomly divided into two groups: the regular dosage group and the large dosage group. At initiation and 30 min after intravenous fasudil(30 mg and 60 mg respectively), the following hemodynamic parameters were measured and calculated: right atrial pressure(RAP), pulmonary arterypressure(PAP) , systemic artery pressure (SAP), pulmonary capillary wedge pressure(PCWP) , pulmonary vascular resistance(PVR) and systemic vascular resistance( SVR), cardiac index (CI) and artery oxygen saturation (SaO₂).

Compared with pre-medication, both mPAP and PVR tended to reduce significantly in the regular dosage group and the large dosage group: mPAP from (63.7±8.6)to (58.3±8.5)mmHg(P<0.01) and from (62.9±8.8) to(55.1±7.8)mmHg (P<0.01), respectively; PVR from(9.9±4.3)to (7.7±3.9) Wood(P<0. 01) and from (9.5±4.9)to(6.1±4.8)Wood(P<0.01); CI tended to increase significantly in the two groups: from (2.9±0.9) to (3.1±1.1) L·min^-1·m^-2( P<0.05) and from(3.0±0.8) to (3.5±1.6) L·min^-1·m^-2( P<0.05), respectively . Compared with the regular dosage group, both mPAP and PVR tended to reduce significantly in the large dosage group: mPAP (8.2±1.8)vs (4.2±1. 0)mmHg (P<0.05); PVR(3.7±1.1)vs (2.1±0.8 ) Wood (P<0.05) .Meanwhile , there was no significant difference in CI, SAP, SVR and SaO₂ between the two groups.

Fasudil could improve the acute hemodynamic effects of patients with CHD and severe PAH, especially in the large dosage group.

To explore the expression and significance of Set gene in Acute myeloid leukemia (AML) patients , and to analyze its effect for the prognosis of AML.

The level of Set gene expression was detected by real-time PCR in 59 AML patients and 20 heathy people. The mutations in C-kit 8/17 gene, NPM1 gene and FLT3-TKD/ITD gene in 59 AML patients were detected by direct sequencing.

The level of Set gene expression[1.41(0.41-3.31)]was significantly higher in 59 AML patients.The expression of Set gene was correlated with the percentage of marrow blasts and CR in AML patients (P=0.040, P<0.001); the CR rate of Set gene high expression group was significantly lower than that of Set gene low expression group(32.1% vs 83.9%,P=0.01). In the intermediate-risk of AML patients with chromosome karyotype analysis, the CR rate of Set gene high expression group and low expression group were 34.8% and 88.9%, and there are significantly different between two groups(P<0.001); univariate and multivariate analysis showed that Set gene high expression group correlated with poor OS[4(2-15)months]and EFS[3(2-13)months])(P=0.021, P=0.017). It suggests that the Set gene maybe one of AML independent poor prognostic marker.The level of Set gene expression did not correlate with sex, age, WBC, HGB, PLT, FAB typing, chromosomal karyotype and NPM1, C-Kit8/17, CEBPa, FLT3-ITD/TKD gene mutations in AML patients(all P>0.05).

The level of Set gene expression in bone marrow maybe play an important role in AML. The high expression of Set gene indicates poor prognosis in AML patients.

To investigate the expression status of anaplastic lymphoma kinase (ALK) fusion gene in lung sarcomatoid carcinoma (LSC) and the role of ALK inhibitors for treatment.

Total of 84 cases of LSC confirmed by histopathology were detected for ALK fusion gene from January 2011 to December 2014 in the Cancer Hospital of Chinese Academy of Medical Science&Peking Union Medical College and Shandong Zibo Wanjie Cancer Hospital. All patients were primarily treated by the multi-disciplinary mode in combination with chemotherapy or targeted therapy based on surgery. Postoperative adjuvant chemotherapy was given on platinum based two-drug combination regimen. In ALK fusion gene (+ ) patients with recurrence or metastasis, crizotinib target therapy was prefered. Chi-square test was applied for the comparison of 1, 3, 5-year survival rates between the two groups.

Eighty-two cases completed the follow-up. ALK fusion gene was found in 9(10.7%) patients. After application of crizotinib, 1 case was evaluated as complete remission, 6 cases as partial response, 2 cases as stable disease; the 1, 3, 5-year survival rate was 100% (9/9), 100% (9/9) and 88.9% (8/9) for the patients with ALK fusion gene, and it was 65.8% (48/73), 15.1% (11/73) and 6.8% (5/73) respectively for patients without ALK fusion gene. There was significant difference in the survival rate between the two groups (χ²=1.56, 1.56, 0.83, all P<0.05).

ALK fusion gene maybe expressed in LSC patients. Compared with conventional chemotherapy, crizotinib can significantly prolong the survival time of patients with ALK fusion gene.

To investigate the predictive value of elevated serum S100B level in patients with multiple traumas combined delirium for the clinical prognosis prior to intensive care unit (ICU) discharge.

One hundred seventy-nine patients with multiple traumas diagnosed as delirium after admission over 48 hours to the Department of Critical Care Medicine, People′s Hospital Affiliated to Jiangsu University from January 2013 to December 2016 were divided into two groups according to the level of serum S100B measured prior to the ICU discharge: high S100B group (≥0.20 μg/L, n=53) and low S100B group (<0.20 μg/L,n=126). The difference of the clinical prognoses between the two groups was evaluated with t or Chi-square test.

The patients in high S100B group had a higher ICU readmission rate (18.9% vs 6.3%, χ ²=6.464, P=0.011). The 30-day mortality was higher for patients in high S100B group than that in low S100B group (5.7% vs 4.0%, χ ²=0.308, P=0.579). The incidence of adverse outcome was also significantly higher for patients in high S100B group than that in low S100B group (35.8% vs 17.5%, χ ²=7.144, P=0.008). The sequential organ failure assessment (SOFA) score before ICU discharge was also higher for patients in the high S100B group than that in the low S100B group (3.2±1.3 vs 2.4±1.1, t=4.204, P=0.000). The duration of ICU stay for patients in high S100B group was significantly longer than that in the low S100B group[(16±8) vs (12±5) d, t=4.095, P=0.000]. The area under the curve (AUC) of receiver operating characteristics of the S100B was 0.742, 95% CI: 0.574-0.910. The multivariate logistic regression analysis revealed that the odds ratio (95% CI) in the prediction of adverse outcomes by S100B level prior to the ICU discharge was 1.39(1.15-1.53), P=0.009.

Elevated serum level of S100B in patients with multiple traumas combined delirium prior to ICU discharge is closely associated with poor clinical prognosis, but it is only a modest predictor that may not be used alone in judgements of clinical treatments for patients.

To analyze the effect of preset adaptive statistical iterative reconstruction-V (ASIR-V) on image quality and radiation dose in dual-enhanced abdominal CT and to investigate the optimal ASIR-V in clinic use.

From February 13 to April 30 in 2017, one hundred and eighty patients who received up abdominal CT scan in the First Affiliated Hospital of Zhengzhou University were collected prospectively. All patients underwent arterial phase (AP) and portal venous phase (PVP) enhanced abdominal CT(120 kVp, noise index 10) and were randomly divided into 6 groups according to random number table (A-F, 30 cases in each group). In group A-F, 0-50% preset ASIR-V (an interval of 10%) was applied, respectively. Qualitative parameters (subjective image quality, diagnosis confidence and radiation dose) and quantitative parameters[image noise, CT number and contrast to noise ratio (CNR)]were measured and compared among the groups by using one-way analysis of variance or Kruskal-WallisH test.

The CT dose index volume (CTDIvol) decreased with the increasing of preset ASIR-V. The effective radiation dose (ED) was significant different among groups (F=27.598, P<0.05), and the ED of group B-F dropped by 10.8%, 21.7%, 31.2%, 44.9% and 61.9% respectively when compared with that in group A. Group E showed the optimal image quality (Z=18.675, 27.548, 19.761, all P<0.05) and diagnosis confidence(Z=21.387, 17.693, 22.459, all P<0.05) in plain scan, AP and PVP phases. There was no significant differences in image noise and CT value of liver, pancreas and muscle among groups (F=1.468, 0.337, 0.592, 0.284, all P>0.05). There were significant differences in CNRs in liver and portal vein in PVP phase among the groups (F=3.980, 4.681, both P<0.05).

In abdominal CT, 40% preset ASIR-V can provides the best image quality and it can reduce radiation dose for 44.9%.

Example 1: Child (1-IV-17), female, 3 years old. He was admitted to the General Hospital of the People's Liberation Army in May 2011 because he was "unable to walk for three years since childhood". The child has difficulty walking since childhood without obvious incentives, abnormal standing posture, touching the ground with both toes, unable to walk alone, and easy to fall. The above symptoms include light morning and heavy evening phenomenon, stiffness of both lower limbs in the afternoon, and obvious at night. Symptoms worsened slowly, there was no abnormality in both upper limbs, and speaking and eating were normal. The local hospital treated it according to "cerebral palsy", but the condition did not improve significantly. Physical examination: The muscle tone of the limbs was gearlike increased, obvious in both lower limbs, active tendon reflex of the limbs, mild inversion of both feet, and bilateral pathological signs (-). Ophthalmic examination did not show K-F rings. Liver and kidney function, serum ceruloplasmin (CP), serum copper and 24-h urine copper were all normal. Brain MRI and neuroelectrophysiological examination were normal. The initial diagnosis was dopa-responsive dystonia (DRD), and the patient was given dopaserazide (trade name Medopa) 62.5 mg, 3 times/d, and functional exercise and equipment rehabilitation therapy were used to help correct foot varus. The patient could walk on his own, and then continued to take Medopa orally at the original dose. After taking the medicine for 1 or 2 years, the patient was stable at outpatient follow-up. After taking Medopa 62.5 mg for a long time, 3 times/d for maintenance therapy, the patient could walk on his own.

The 56-year-old female was admitted to the Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology on May 6, 2017 due to intermittent epigastric pain for more than 10 years and recurrence with melena for 3 days. More than 10 years ago, the patient had intermittent upper abdominal pain without obvious trigger, which was obvious when hungry and could be relieved after eating. The abdominal pain recurred, intermittently accompanied by melena, and no formal diagnosis and treatment was given. Three days before admission, abdominal pain recurred, accompanied by melena, black shaped stools were defecated once a day, with a amount of about 150 g, and palpitations occurred after defecation. Physical examination at admission: anemic appearance, flat abdomen, no gastrointestinal type, soft abdomen, mild tenderness in the upper abdomen, no rebound pain and muscle tension in the whole abdomen, and normal intestinal sounds. Blood routine after admission, red blood cell count 1.92×10¹²/L, hemoglobin 61 g/L. Stool routine showed positive occult blood. Gastroscopy showed a bulging lesion on the anterior wall of the lower part of the stomach body, with clear boundaries, about 4.0 cm ×4.0 cm, covered with white coating, and the biopsy was tough (Figure 1)。 Microscopic diagnosis: (1) The nature of gastric body bulge type lesion to be determined-gastric stromal tumor? (2) gastric fundus polyps; (3) Chronic non-atrophic gastritis with erosion. Pathological examination of gastroscopic biopsy showed that the gastric fundus polyps were mild chronic active mucosal inflammation, and the gastric body mass submitted for examination was inflammatory necrotic tissue. After the patient's anemia was improved, surgical exploration was performed. During the operation, the anterior wall of the great curvature of the stomach was longitudinally incised. A spherical mass, about 4 cm in diameter, intracavitary, smooth, medium texture, good mobility, no gastric mucosal layer covered, surface ulcer formation was seen, and the base was close to the gastric angle. The mass was completely removed and the pathology was submitted for examination. Postoperative pathological report (Figure 2): Gastric angle mass dendritic fibromyxoid lipoma (DFML), the tumor size is 3.5 cm ×2.7 cm ×2 cm, the main tumor body is located in the submucosal layer, and the mucosal layer is involved to form superficial ulcer. Immunohistochemical results: STAT6 (cytoplasmic +), CD34 (partial +), Bcl-2 (+), CD99 (weak +), ALK (-), DOG-1 (-), CD117 (-), β-catenin (-), HMB45 (-), actin (smooth muscle +), S-100 (-). After operation, he was given routine fasting, acid suppression, anti-inflammatory, fluid rehydration and other treatments. He recovered well after operation, with no progression of anemia, and routine occult blood in feces turned negative. He has recovered and been discharged.

Pituitary tumors are one of the most common intracranial tumors in clinic, with a population incidence of about 9 in 10,000. According to the level of hormone secretion, pituitary adenomas are classified into functional pituitary adenomas and non-functional adenomas. Functional pituitary tumors are mainly divided into prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH)^[1]。 The mechanism of pituitary tumors is still unclear, but some studies have shown that it is formed by the activation of oncogenes, inactivation of tumor suppressor genes and downregulation of microRNA. There is also the involvement of certain cytokines, such as interleukin-6 (IL-6) and the like. It is worth pointing out that IL-6 is involved in the progression of tumor cell senescence and may act as a mechanism for pituitary tumors to maintain benign growth^[2,3]。 The clinical manifestations of pituitary tumors are abnormal hormone secretion, neurological symptoms caused by tumor compression of peripituitary tissues, pituitary stroke, and other anterior hypopituitary function. At present, the treatment methods of pituitary adenoma mainly include surgery, radiotherapy and drug therapy, among which dopamine receptor agonist treatment is the first choice for patients with PRL tumor. Recently, immunotherapy has developed rapidly in tumor treatment, and has achieved remarkable clinical results. Among them, blocking the immunosuppressive target (PD-1) on the surface of T cells to activate the immune function of T cells has been approved by the FDA as a treatment for melanoma, lung cancer and kidney cancer. At the same time, the research of immunotherapy in the treatment of pituitary tumors continues to make progress, and it is expected to become an important treatment after surgery, radiotherapy and drug therapy^[4]。

With the aging of the population, the incidence of osteoporosis is increasing year by year, and it has gradually become one of the global health problems to be solved urgently^[1,2]。 China is a country with a high incidence of osteoporosis. According to the national epidemiological survey from 2003 to 2006, the prevalence rate of osteoporosis among people over 50 years old in China is about 14.4% in men and 20.7% in women, which brings a huge economic burden to the families and society of patients^[2]。 Primary osteoporosis is mainly divided into postmenopausal osteoporosis (type I) and senile osteoporosis (type II). Pathologically, the main manifestations are bone mass reduction per unit volume, bone microstructure degradation and bone strength reduction. The former is mainly associated with decreased estrogen levels and increased osteoclast activity, while the latter is mainly age-related physiological degeneration^[2]。 Fractures are the most common complication of osteoporosis, among which non-traumatic fractures of the hip, femoral neck and spine are the most common and are the main causes of paralysis and death in patients^[2,3]。

Cholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelial cells, which can occur in any part of the bile duct tree. According to the anatomical location, it can be divided into intrahepatic Cholangiocarcinoma (iCCA), hilar Cholangiocarcinoma (pCCA), and distal Cholangiocarcinoma (dCCA)^[1]。 Epidemiological data show that the incidence and prevalence of cholangiocarcinoma are increasing worldwide, and the mortality rate is increasing accordingly^[2]。 Although the tumor grows slowly and metastasizes late, due to the special anatomical site of cholangiocarcinoma, coupled with its characteristics of infiltration and spread along blood vessels and nerve sheaths, it is usually at an advanced stage when discovered, and radical surgery is often difficult to achieve the expected efficacy. Most patients with unresectable tumors die of liver failure or biliary obstruction within one year^[1,3]Cholangiocarcinoma is seriously threatening the lives of patients. At present, it is believed that the occurrence and development of cholangiocarcinoma is a multi-factor and multi-step pathological process, which involves the activation of oncogene, inactivation of tumor suppressor gene, tumor metastasis, apoptosis and abnormal cell cycle regulation, tumor genetics and epigenetic changes, etc^[4]。 Wnt signaling pathway is a highly conserved signaling pathway in animals and plants, which regulates and controls many life processes, including growth, development, disease, aging and death of organisms. It also includes differentiation and maintenance of cell morphology and function, immunity, stress, cell carcinogenesis and apoptosis^[5,6]。 Wnt signaling pathway is also closely related to tumorigenesis, and it has been reported that it is related to the origin of many tumors^[7,8]It has been found that the Wnt signaling pathway can lead to the occurrence and development of cholangiocarcinoma by activating its downstream target genes. Wnt pathway and its research progress in cholangiocarcinoma are discussed in this paper.