Volume 96  ·  Issue 30  ·  2016

Continuous positive airway pressure (CPAP) is widely used in clinic as the first choice treatment for obstructive sleep apnea hypopnea syndrome (OSAHS), but its compliance is not ideal^[1]。 The factors affecting adherence include disease and treatment factors, and involve psychological and social factors, etc. Therefore, for each individual, a comprehensive analysis should be carried out based on the bio-psychosocial (BPS) model to propose integrated strategies for coping^[2]。 For a variety of chronic diseases, including OSAHS, integration strategies are essential for improving treatment adherence, and their efficacy, as the ancient Greek philosopher Aristotle said, "the whole is greater than the sum of its parts."^[2]。

In recent years, the outpatient clinic of pituitary-gonadal diseases in the Department of Endocrinology of Peking Union Medical College Hospital often receives such male infertility patients who are repeatedly referred but unknown in diagnosis. Their "sex hormone" levels are close to normal, and they are often diagnosed as "idiopathic male infertility". If you carefully inquire about the medical history and physical examination, it can be found that their height before puberty is significantly higher than that of children of the same age. After adulthood, they often show infertility after marriage, short stature, dark skin, small or unsmooth testicles or even nodular feeling. The levels of blood progesterone and 17-hydroxyprogesterone are high, and they are diagnosed as 21-hydroxylase deficiency (21-hydroxylase deficiency, 21OHD) after further examination.

To analyze subtypes of the clinical presentation of moderate-to-severe obstructive sleep apnea syndrome (OSAS) by cluster analysis and to explore its significance.

A retrospective analysis was performed on the data of adult moderate-to-severe OSAS patients, which were diagnosed in Respiratory Department, Renmin Hospital of Wuhan University from October 2012 to October 2015. Fifteen kinds of clinical presentations were included in the cluster analysis, and analysis of characteristic of each cluster was then performed after category.

Patients were classified as three distinct clusters. They were identified as "daytime sleepiness group" , "night insomnia group" and "minimally symptomatic group" , consisting of 450 cases (44.64%), 351 cases (34.82%) and 207 cases (20.54%) of the entire cohort. Members in daytime sleepiness group had the highest probability of daytime sleepiness, tiredness, irritableness and the highest Epworth Sleeping Scale score[329 cases (73.11%), 280 cases (62.22%), 223 cases (49.56%) and (13.50±4.93) points], members in night insomnia group had the highest probability of complaining of insomnia, nocturia, night sweats, apnea and awakening[177 cases (50.43%), 157 cases (44.73%), 130 cases (37.04%), 296 cases (84.33%), 182 cases (51.85%)], the probability of having typical symptoms above was the lowest in minimally symptomatic group, but these patients were more likely to have related comorbidities: hypertension, coronary heart disease, arrhythmia, chronic obstructive pulmonary disease and gastroesophageal reflux disease[118 cases (57.00%), 41 cases (19.81%), 44 cases (21.26%), 34 cases (16.43%), 38 cases (18.36%)]; all above results were significantly higher than the other two groups ( P<0.012 5). The rate of diabetes in minimally symptomatic group[28 cases (13.53%)]was also higher but the difference was not statistical significance.

Cluster analysis contributes to classify multiple clinical presentations of OSAS patients, which has important significance for recognizing disease heterogeneity and early diagnosis.

To explore the continuous positive airway pressure (CPAP) therapy compliance in patients with obstructive sleep apnea (OSA).

This prospective study recruited a group of subjects from May 2009 to December 2013 who were diagnosed and had accepted CPAP treatment in Sleep Center of Guangdong General Hospital, and the patients were followed-up regularly for long-term and assessed the CPAP treatment compliance. The patients were diagnosed, had pressure titration and CPAP treatment through out of center sleep test. The subjects were followed-up for 1 st, 3rd, 6th, 12th month, and each year regularly after accepting the CPAP treatment in Sleep Center by face to face follow-up with specialist physicians. Physicians followed-up the patients′ subjective symptoms, CPAP adherence, patient education and side effect solutions. The patients were classified into good and poor compliance groups, and statistical analysis was done between the two groups.

There were 77 cases enrolled until December 2015, only 73 patients completed the study. The patients were followed-up about 2-6 years, the average was (3.93±1.29) years, the compliance accounted for 54.8% (40/73), and the average compliance was (4.02±1.87) hours/night. The trend of the long-term compliance showed that there was a gradual increase within the first 3 months of CPAP treatment and then the compliance decreased; it then increased gradually after the first two years. The good compliance group showed that the compliance increased gradually in the initial 3 months, and then fell; from the first year to the 3rd year, the compliance was stable; after the 3rd year there was a drop and the compliance tended to increase again after the 4th year. The poor compliance group showed the compliance had a downward trend from the beginning of the first two years, then after a brief rise, the compliance decreased linearly. Multivariate analysis showed that long-term compliance was not associated with age, daytime sleepiness (ESS), oxygen desaturation index (ODI), anxiety, depression (P>0.05), etc. However, it was associated with the time of the titration treatment (P<0.001), the time of the flow monitored (P<0.01) and the number of the pressure titration within one week (P<0.05).

Long-term compliance shows a curve change, the increased compliance is related with the regular follow-up. Long-term compliance can be predicted by the degree of cooperation with the initial diagnosis and treatment.

To explore the correlation between intermittent hypoxia (IH)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and release of cytochrome C (cytC) from mitochondria.

HUVECs in IH groups were exposed to repetitive cycles (1% O₂ 5 min alternating with 21% O₂ 5 min, 37 ℃, 5% CO₂) for different exposure time (8, 16 and 24 h, respectively), while the control group were placed in an ordinary incubator (21% O₂, 37 ℃, 5% CO₂) for 24 h. Apoptosis rate of HUVECs were determined by using Annexin V-FITC/PI apoptosis detection kit. The mitochondria ultrastructure was observed under transmission electron microscope (TEM). The mitochondria and cytoplasm of HUVECs were isolated by differential centrifugation, and the expression cytC in two separations were detected by Western blot. The correlation between the release of cytC and apoptosis rate was analyzed.

TEM showed that mitochondria in HUVECs treated with IH appeared significant swelling, cristae rupture and vacuolization, compared with intact mitochondria in control group. Apoptosis rates in IH groups of 8, 16 and 24 h were significantly higher than control group[(6.710±0.599)%, (8.863±1.190)% and (9.607±1.266)% vs (2.450±0.795)%]in a time-dependent manner (all P<0.05). Apoptosis rates in IH groups positively correlated with cytC expression in cytoplasm (r=0.741, P=0.022).

IH-induced cytC release from mitochondria promotes apoptosis of HUVECs, which participates in IH-induced endothelial injury.

To investigate the association of Crohn′s disease (CD) with transcobalamin Ⅱ (TCN2) gene polymorphisms and serum homocysteine (Hcy), folate, and vitamin B₁₂ levels in Chinese patients.

In a total of 307 CD patients (CD group) and 574 healthy controls (control group) of Han ethnicity selected at 4 hospitals in Wenzhou between January 2007 and August 2015, TCN2 gene polymorphisms (rs1801198, C/G; rs9606756, A/G) in peripheral blood were determined using improved multiple ligase detection reaction (iMLDR). The Simplified Crohn′s Disease Activity Index (CDAI) was applied to evaluate activity of CD. Eighty-eight CD patients and 138 age- and sex-matched controls were randomly selected from all the study subjects using computer-generated random numbers, in whom serum Hcy level was tested by enzymatic cycling assay, folate and vitamin B₁₂ levels were examined by chemiluminescence immunoassay.

(1) The mutant allele (G) and genotype (CG+ GG) of rs1801198 were not significantly different between the CD group and the control group (both P>0.05), but more prevalent in patients with stricturing CD than in controls (65.75% vs 56.10%, 93.15% vs 82.40%, bothP<0.05). The frequencies of mutant allele (G) and heterozygous genotype (AG) of rs9606756 were higher in CD patients than in controls (2.44% vs 1.05%, 4.89% vs 2.09%, bothP<0.05), also higher in patients with stricturing CD or ileocolonic CD compared with controls (stricturing CD: 4.79% vs 1.05%, 9.59% vs 2.09%; ileocolonic CD: 3.18% vs 1.05%, 6.36% vs 2.09%; allP<0.05). The two polymorphic loci (rs1801198 and rs9606756) were shown to be in a weak linkage disequilibrium. The frequency of haplotype (GG) was higher in the CD patients than in the controls (2.23% vs 0.81%,P<0.05). (2) When compared with the controls, the serum Hcy level was higher in the CD patients (P=0.023), whereas the folate and vitamin B₁₂ levels were decreased in the CD patients (both P<0.001). The prevalence of hyperhomocysteinemia (Hcy >15 μmol/L), folate deficiency (folate <4 μg/L) and vitamin B₁₂ deficiency (<203 ng/L) were higher in the CD patients than in the controls (18.18% vs 4.35%, 27.27% vs 5.07%, 31.82% vs 5.07%, allP<0.01). Compared to the patients at remission stage (CDAI<5), the serum Hcy level was increased in those at active stage (CDAI≥5) (P=0.005), while the folate and vitamin B₁₂ levels were decreased in the patients ate active stage (both P<0.05). (3) According to the results of multivariate linear regression analysis, average Hcy level in the CD patients was negatively associated with folate level (β=-0.494,P<0.001), while positively correlated with percentage of neutrophils (β=0.294,P=0.004). Unconditional Logistic regression showed that both folate deficiency and vitamin B₁₂ deficiency were independent risk factors for CD (OR=5.415, OR=7.112, both P<0.001).

TCN2 rs1801198 mutation might be associated with increased risk of stricturing CD. TCN2 rs9606756 mutation might be a potential functional locus to affect CD susceptibility. Individuals carrying the haplotype (GG) formed by TCN2 (rs1801198 and rs9606756) seem to be at higher risk of developing CD. Hyperhomocysteinemia, folate deficiency, and vitamin B₁₂ deficiency are prevalent in this cohort of CD patients of Han ethnicity from Zhejiang province. Both folate deficiency and vitamin B₁₂ deficiency are independent risk factors for CD.

To investigate the bowel symptoms and psychological status of patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D), and to verify whether sigmoid colon mucosal mast cells (MCs) and their activation have effect on the symptoms and psychological status of IBS-D patients.

Patients meeting Rome Ⅲ diagnostic and subtyping criteria of IBS-D who visited the outpatient clinic of gastroenterology of Peking Union Medical College Hospital were consecutively enrolled between July 2009 and June 2012. IBS symptoms questionnaire was completed using face-to-face interview, and Hamilton Anxiety Scale (HAMA)/ Hamilton Depression Scale (HAMD) were administrated to evaluate psychological status, both by well-trained investigators. Mast cell tryptase monoclonal antibody was used for immunohistochemical staining to detect MCs and degranulated MCs in mucosal biopsy of sigmoid colon. MCs and degranulated MCs were blindly counted by a senior pathologist, and presented as number of cells in high power field (HPF) and percentage of activated MCs. Correlation analysis was performed using Spearman rank correlation analysis.

Ninety-seven patients with IBS-D were enrolled in this study, with mean age of (44±11) years. 70.10%(68 cases) of the IBS-D patients had comorbid anxiety and/or depression. The median total numbers of MCs, activated MCs, and percentage of activated MCs in sigmoid mucosa were 11.60 (7.09)/HPF, 2.00 (1.40) /HPF, and 17.50% (10.90%), respectively. Patients having abdominal pain/discomfort before bowel movement "every day with intermediate to high severity" had significantly larger numbers of total MCs in sigmoid colon compared with those with pain or discomfort "not every day and mild" [13.80(4.85)vs 7.60(5.90)/HPF, P=0.019]; the patient having "frequent" urge to have a bowel movement and mushy stools showed significantly higher percentage of activated MCs in sigmoid colon mucosa compared to those having the symptoms "some of the time" [18.75%(9.12%) vs 14.50%(13.14%), P=0.031; 21.33%(7.43%)vs 11.51%(10.65%)vs 18.42%(8.61%), P=0.030]. There was a positive correlation between the bowel movement during IBS-D onset and the percentage of activated MCs (r=0.221, P=0.030). There were no statistically significant differences in the total number of MCs and percentage of activated MCs between the patients with anxiety/depression and those without anxiety/depression (P=0.255, P=0.315). Scores of HAMA and HAMD were found not correlated with either total MCs number or percentage of activated MCs in sigmoid colon mucosa(all P>0.05).

The majority of IBS-D patients had comorbid anxiety and/or depression. The total number and activation status of MCs in sigmoid colon mucosa might be related with some intestinal symptoms in IBS-D patients. Psychological disorders might influence the pathogenesis and regression of IBS-D through brain-gut axis other than MCs in sigmoid colon mucosa.

To investigate the effect of proteinuria on in-hospital severe adverse events and prognosis of the patients with heart failure(HF).

Clinical data of 520 patients with severe HF( NYHA 3-4 grades) in our department were analyzed retrospectively. Proteinuria was diagnosed on admission using the spot dipstick urinalysis. Clinical characteristics were compared between the patients with and without proteinuria. Univariate and multivariate Logistic regression analysis were used to evaluate the correlations of proteinuria with in-hospital adverse events and prognosis.

On admission, proteinuria was found in 57.7% (300/520) of the enrolled patients with severe HF. The age, proportions of the HF patients coexistent with hypertention, diabetes mellitus and aneamia, and receiving vasoactive drugs, levels of NT-proBNP, creatinine, C-reactive protein and fasting blood glucose, were significantly higher, while the levels of eGFR, hemoglobin and hematocrit significantly lower in the proteinuria group than those in the non- proteinuria group. The multivariate analysis revealed that proteinuria was an independent risk factor for mechanical ventilation (MV) (OR=2.916, 95% CI: 1.712-4.968, P<0.001), cardiopulmonary resuscitation (CPR) (OR=1.956, 95% CI: 0.997-3.843, P=0.049) and in-hospital mortality (OR=2.490, 95% CI: 1.188-5.218, P=0.016).

The severe HF patients with proteinuria often present with severe critical conditions. Proteinuria should be a potential marker for in-hospital adverse events and prognosis of severe hospitalized HF patients.

To summarize our experience in the management of stent-graft infection after endo-vascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA).

Data of patients who were diagnosed as endo-graft infection following EVAR and admitted in our center between January 2000 and December 2015 were reviewed. Clinical records including causes of infection, medical history, re-operative procedures, and prognostic data were analysed.

A total of 10 male patients, aged 45-72 years (averaged 62.5 years), were enrolled. Two patients received previous EVAR in our center, accounting for 0.23% of all the 885 EVAR procedures we conducted during the same period. The symptoms related to stent infection, including recurrent fever (100%) and persistent back pain (40%), occured 0 to 27 months (averaged 6.9 months) after EVAR procedure. Eight patients were found to have apparent causes (80%), including 1 case with upper respiratory infection and sepsis, 4 cases with aorto-enteric fistula (AEF) and 3 cases with inflammatory AAA. Except one DNR, other 9 patients received re-operation, including 1 procedure of open debridement and drainage, 1 procedure of endo-graft excision and bilateral axillary-femoral bypass, 7 procedures of endograft excision and axillary-bifemoral bypass. During the follow-up period(2-60 months, averaged 24.1 months), 1 patient was lost, 1 patient died from aortic stump rupture (12.5%) and other 7 patients survived. Bypass occlusion was observed in 1 patient (12.5%) without severe limb ischemia.

AEF and inflammatory AAA are two leading causes of endo-graft infection following EVAR in our patients. Graft excision and axillofemoral bypass is an acceptable management for this life-threatening morbidity.

To investigate the impact of placement in the procedures of gynecological laparoscopies or routine placement on the effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for symptomatic adenomyosis in a prospective cohort study.

From December, 2006 to December, 2014, patients with adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital received the treatment of LNG-IUS.Before and after placement of LNG-IUS all the parameters were recorded including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects.Impact of placement timing (in the procedures of laparoscopies vesus routine placement) on the treatment effects, menstruation patterns and adverse effects of LNG-IUS were analyzed.

1 100 patients meet the inclusion criteria, with median age 36 years (20-44 years), median follow-up 35 months (1-108 months), of which 385 cases (35.0%) received LNG-IUS in the procedures of gynecological laparoscopies. Most common indications and pathology outcomes were endometriosis, major of which had deep infiltrating endometriosis. The accumulative carrying ratio of LNG-IUS were 73% and 63% on 60 months for operative patients and non-operative patients respectively (P<0.001), and accumulative take-out ratio were 7.8% and 10.3% (P=0.044). Placement timing of LNG-IUS was the only significant factor related with loss to follow-up (P<0.001) and take-out ratio (P<0.001). Operations and pathological outcome had no significant impact on patients′ treatment effects, changes of menstruation patterns, adverse effects in total or in subclass.

Placement of LNG-IUS in the procedures of gynecological laparoscopies for symptomatic adenomyosis increased carrying ratio and reduce take-out ratio at patients′request, but didn′t influence treatment effects or adverse effects.

To investigate the protein content and protein expression of MMP-9 and AQP-9 in the placenta of patients with hypertensive disorders complicating pregnancy.And to investigate the mechanism of magnesium sulfate in the treatment of hypertensive disorders complicating pregnancy.

The patients with hypertensive disorders complicating pregnancy were divided into treatment group (n=51) and untreated group (n=45), and 20 cases of normal pregnant women were selected as the control group. The three groups were taken from the placenta after delivery. ELISA and immunohistochemistry method were used to detect the protein content and protein expression of AQP-9 and MMP-9 in placenta of each group.

The protein contents and protein expression of MMP-9 in placenta tissues of treatment group were 5.89±0.52 and 125.2±0.5; AQP-9′s were 4.3±0.5 and 110±4. The protein contents and protein expression of MMP-9 in placenta tissues of untreated group were 1.85±0.26 and 148.6±5.2; AQP-9′s were 9.4±0.8 and 92±3. The protein contents and protein expression of MMP-9 in placenta tissues of control group were 6.13±0.84 and 120.7±4.4; AQP-9′s were 4.1±0.7 and 114±3. Compared with the control group, the protein contents and protein expression of MMP-9 in placenta tissues of untreated group were significantly decreased, and that of AQP-9 was significantly increased, both with the statistically significant difference (P<0.01). The protein contents and protein expression of MMP-9 protein in placenta tissues of the treatment group were slightly lower, AQP-9 was intensity increased (bothP>0.05).

Magnesium sulfate can increase the level of MMP-9 protein and down regulate the protein level of AQP-9, which may be one of the effective mechanisms of the treatment of hypertensive disorders complicating pregnancy.

To clarify the advantages and the influence to reproductive outcome after laparoscopic salpingotomy with and without suturing for tubal pregnancy.

We retrospectively analyzed the clinical data of patients underwent laparoscopic salpingotomy from March 2012 to October 2014 who were willing to reserve their reproductive function and were able to be followed up. Based on the operation procedure, the patients were assigned to undergo laparoscopic salpingotomy with suturing (group A; n=49) or without suturing (group B; n=69). An amount of 50 mg methopterin was injected at mesosalpinx during operation in all cases. Tubal patency of the trouble side was evaluated by liquid instillation. The operation time, amount of bleeding, the trouble side tubal patency rate 3 months after the surgery, pregnancy outcome 12 months after the surgery was compared between two groups.

Three months after the surgery the tubal patency rate of trouble side was 85.71% (42/49) in group A and 62.32% (43/69) in group B. There was significant differences (P<0.05) between two groups. Within twelve months of the surgery, the intrauterine gestation rate was 69.39% (34/49) in group A and 42.03% (29/69) in group B. Ectopic re-pregnancy rate of the trouble side was 10.20% (5/49) in group A and 27.54% (19/69) in group B. Secondary infertility rate was 14.29% (7/49) in group A and 27.54% (19/69) in group B. There was significant differences (P<0.05) between two groups. The trouble side tubal patency rate and intrauterine gestation rate of group A was significantly higher than that of group B, while the ectopic re-pregnancy rate of the trouble side and secondary infertility rate of group A was significantly lower than that of group B.

Suturing after laparoscopic salpingotomy can decrease the damage to fallopian tube and recover its normal anatomic structure. So the procedure involving suturing can effectively reserve reproductive function for the patients.

To compare the effects on wound bed of deep burn following eschar excision with different wound management in rabbits.

Eighteen full-thickness burns models of Japanese white rabbits were established. They were randomly divided into 3 groups of traditional dressing, biological dressing and negative pressure wound therapy (NPWT) (n=6 each), according to the random number table. Eschar excision was performed three days later. The wound bed was observed and wound tissue was harvested for counting the quantity of bacteria, tissue dry wet ratio, measuring the level of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β and IL-6, the amount of collagen fibers and the microvessel density instantly and again seven days later. Statistical analyses were performed.

The NPWT group was better than other groups by observing the wound bed. The quantity of bacteria of traditional dressing group, biological dressing group and NPWT group at the time point of seven days after escharectomy turned out to be (9.4±1.5)×10^4, (8.1±2.7)×10^4, (3.9±0.7)×10⁴ cfu/g, the NPWT group was significantly lower than traditional dressing group and biological dressing group (both P<0.05), and all lower than that at the time point of the day when escharectomy was performed (576.9±169.5)×10^4, (589.9±99.6)×10^4, (583.0±160.4)×10⁴ cfu/g ( all P<0.05). There were no statistically significant differences among three groups at two time points in tissue dry wet ratio (allP>0.05). The IL-6 of biological dressing group was higher than that of traditional dressing group at the time point of seven days after the eschar excision was performed[(94±10) vs (76±8) ng/L,P<0.05]. The amount of collagen fibers of three group at the time point of seven days after escharectomy turned out to be (60±9), (55±12), (77±17). The NPWT group was significantly higher than traditional dressing group and biological dressing group (P<0.05), and all higher than that at the time point of the day when escharectomy was performed[(39±6), (39±11), (38±6)](allP<0.05). The microvessel density of three groups at the time point of seven days after escharectomy turned out to be (42±6), (53±4), (82±10). The NPWT group was higher than that of the other two groups, and biological dressing group was higher than that of traditional dressing group (allP<0.05). The biological dressing group and NPWT group were both higher than that of the day when the eschar excision was performed (36±5) and (36±5) (P<0.05).

NPWT is the optimal selection for wound to inhibit the growth of bacteria, promote the accumulation of collagen and tissue vascularization. But these managements have similar effects on reducing tissue edema and inflammatory reaction.

Three dimensional (3D) printing technique was used to prepare the simulate craniocerebral models, which were applied to preoperative planning and surgical simulation.

The image data was collected from PACS system. Image data of skull bone, brain tissue and tumors, cerebral arteries and aneurysms, and functional regions and relative neural tracts of the brain were extracted from thin slice scan (slice thickness 0.5 mm) of computed tomography (CT), magnetic resonance imaging (MRI, slice thickness 1mm), computed tomography angiography (CTA), and functional magnetic resonance imaging (fMRI) data, respectively. MIMICS software was applied to reconstruct colored virtual models by identifying and differentiating tissues according to their gray scales. Then the colored virtual models were submitted to 3D printer which produced life-sized craniocerebral models for surgical planning and surgical simulation.

3D printing craniocerebral models allowed neurosurgeons to perform complex procedures in specific clinical cases though detailed surgical planning. It offered great convenience for evaluating the size of spatial fissure of sellar region before surgery, which helped to optimize surgical approach planning. These 3D models also provided detailed information about the location of aneurysms and their parent arteries, which helped surgeons to choose appropriate aneurismal clips, as well as perform surgical simulation. The models further gave clear indications of depth and extent of tumors and their relationship to eloquent cortical areas and adjacent neural tracts, which were able to avoid surgical damaging of important neural structures.

As a novel and promising technique, the application of 3D printing craniocerebral models could improve the surgical planning by converting virtual visualization into real life-sized models.It also contributes to functional anatomy study.

A 60-year-old female, with intermittent cough and shortness of breath for more than 4 years, and left chest pain for 10 days, went to the outpatient department of respiratory medicine, Xiangya Hospital, Central South University on March 12, 2012. The patient developed shortness of breath without obvious trigger 4 years ago, "cold" and aggravation after activity, which can be relieved after rest, and cough gradually appeared, coughing a small amount of white or yellow phlegm. In the past 4 years, the above-mentioned symptoms have recurred, and the self-reported use of antibiotics and traditional Chinese medicine treatment (details are unknown) has no obvious effect. Ten days ago, there was no obvious trigger for left chest pain, which was pulling-like pain, which could be tolerated, and obviously aggravated after coughing and forced inhalation. The patient did not have cyanosis, fever, night sweats, anorexia, fatigue, hemoptysis, emaciation, etc. since the onset of the disease. Physical examination showed tenderness in the left chest area, but no obvious positive signs of chest were found. Chest X-ray (Figure 1) shows "interstitial lesions and infection of both lungs". High-resolution and plain-scan enhanced three-dimensional CT of lung (Figure 2) shows "enlargement of hilar and mediastinal lymph nodes in both lungs, multiple patches, cystic shadows and small nodules in both lungs, considering the possibility of proliferative lesions of the lymphatic system, lymphoma and lung cancer to be excluded". For further diagnosis and treatment, he was admitted to the respiratory department of Xiangya Hospital of Central South University on March 17, 2012.

A 14-year-old male developed polydipsia, polydipsia and polyuria without obvious trigger one month ago. The urine volume was roughly equivalent to the drinking water volume, and the urine color was clear. The urine specific gravity was checked at the local hospital, 1.005, Yu (-); Water-free-pressure test: 8 hours of water-free urine volume 110-330 ml/h, urine specific gravity 1.003-1.006, urine volume reduced to 15-60 ml/h, urine specific gravity 1.010-1.018 after 5 U of pituitrin administration; Considered for central diabetes insipidus income Peking Union Medical College Hospital. After admission, the relevant examinations were completed: endocrine aspects: the levels of growth hormone (GH), insulin-like growth factor 1 (IGF1), follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), total blood cortisol (F), 24-h urine free cortisol (UFC), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were normal, and blood prolactin (PRL) was 18.14 μ g/L↑ (2.64-13.13); Serum levels of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and β-chorionic gonadotropin (β-hCG) were normal; Blood angiotensin converting enzyme (ACE) levels were normal; Cerebrospinal fluid routine and biochemistry (-). In terms of imaging, plain pituitary scan + enhanced MRI showed that the pituitary stem was thickened, uniformly and significantly enhanced, and the T1 hyperintensity in the posterior pituitary lobe disappeared (Figure 1)； Chest high-resolution CT + enhancement showed small nodules in the lower lobe of the right lung; Thyroid ultrasound revealed diffuse thyroid lesions; Whole body bone imaging showed no abnormalities. Preliminary diagnosis: sellar germinoma. A biopsy is planned to confirm the diagnosis. Sellar area exploration by nasosphenoidal sinus approach showed tough, gray-white tumor tissue in the saddle during operation, and the blood supply was not abundant; Tumor specimens were retained by forceps for frozen pathological examination. In vivo histopathology report: a small number of tumor tissues with large amount of eosinophilic infiltration, excluding Langerhans histiocytosis "; Paraffin pathology report: lesions consistent with Langerhans histiocytosis" (Figure 2), immunohistochemistry AE1/AE3 (+), CD1a (+), Langerin (+), CD34 (+), CD68 (+), CgA (+), EMA (-), Ki-67 (index 1%), OCT3/4 (-), S-100 (+), SALL-4 (-), Vimentin (+), GFAP (-), Calretinin (-), WT-1 (-). Exact diagnosis: Langerhans histiocytosis (LCH).

A 72-year-old male was admitted to the hospital for "1 1/2 years after gastric cancer surgery, hard mass in the left inguinal area and pain for 3 months". One and a half years ago, the patient underwent "exploratory laparotomy + intestinal adhesion release + extended radical resection of gastric cancer + partial transverse colonectomy + partial left lateral lobectomy" in the Department of Gastrointestinal Surgery of the First Affiliated Hospital of Sun Yat-sen University due to "gastric cancer". The postoperative pathology showed moderately-poorly differentiated adenocarcinoma of the residual stomach. The tumor invaded the left external lobe of the liver and transverse mesocolon, and 20 lymph nodes did not metastasize. The postoperative pathological stage was pT4bN0M0, stage ⅢB. The patient did not undergo chemotherapy after operation. In the past 3 months, the patient developed a mass in the left inguinal area with pain, obvious traction pain in the left inguinal area when walking, accompanied by persistent pain on the lateral side of the left femur, and mild edema of the left lower limb. Physical examination: cachexia physical appearance, no swollen lymph nodes were palpable in the supraclavicle and neck, a raised mass was seen in the left inguinal area, and the surface skin shrunk with orange peel-like changes. Palpation could see a hard cord-like mass and extend outward to the iliac fossa. The size of the mass was about 8 cm ×2 cm ×2 cm, with unclear boundary, fixed position, mild tenderness, and left testis retracted to the head. The left iliac fossa palpated with a hard mass, which was fixed and without tenderness. Mild depressed edema of the left lower limb without varicose veins. Digital rectal examination did not palpate the mass. Preoperative serum carcinoembryonic antigen (CEA): 6.17 μ g/L, CA199>1 200 U/ml. Abdominal CT (FIG. 1A，B), whole body PET-CT (Figure 1C) and MRI (Figure 1D) All examinations considered left spermatic cord metastasis, and no signs of recurrence and metastasis were seen in other parts of the abdominal cavity. Biopsy under local anesthesia was performed, and the pathology was moderately-poorly differentiated adenocarcinoma. Compared with the previous pathology of gastric cancer, the characteristics of the two were consistent. The patient received oral Tigeo chemotherapy (40 mg, twice/d) for 28 d as a course of treatment. After 4 sessions of chemotherapy, chemotherapy was discontinued due to severe toxic side effects, and at the same time, local palliative radiotherapy in the left inguinal area was received for 45 Gy. After 10 months follow-up, the lesions were stable.

Itraconazole, first synthesized in 1980, is a triazole antifungal agent whose triazole ring is located in the side chain of the molecule and is the active site of itraconazole. Itraconazole can inhibit the ergosterol synthesis mediated by membrane pigment P450 oxidase, which in turn inhibits the growth of fungi^[1]Widely used clinically for a variety of fungal infections. In recent years, it has been found that itraconazole has a variety of non-antifungal effects. Basic research has found that itraconazole has anti-angiogenesis, inhibits Hedgehog (Hh) signaling pathway, induces autophagy, upregulates the expression of hypoxia-inducible factor-1 α, inhibits mammalian target of rapamycin (mTOR), regulates cholesterol transport, inhibits P-glycoprotein, etc. Clinical studies have found that itraconazole is effective for some cancers/tumors, infections and inflammatory diseases, especially for a variety of refractory tumors. This is a systematic review of the progress in the non-antifungal effects of itraconazole associated with human diseases.

Since the 1980s, the application of extracorporeal shock wave therapy (ESWT) has opened a new chapter in physical medicine^[1]Together with CT and MRI, it is known as the three new medical technologies in the 20th century. low intensity of extracorporeal shock wave therapy (LiESWT), as an effective, painless and non-invasive physical therapy, not only effectively removes urinary stones, but also promotes neovascularization and improves microcirculation^[2]Treating male erectile dysfunction (ED)^[3]Relieve chronic pain^[4]and accelerated wound repair^[5]And other aspects have been increasingly paid attention by clinical and scientific research centers at home and abroad. The successful independent research and development of "wide focal spot-low intensity" shock wave therapy instrument in China has also attracted much attention from the world. The new progress of LiESWT, represented by "wide focal spot-low intensity" shock wave therapy, in the field of urological andrological diseases medicine is introduced as follows.