Volume 98  ·  Issue 02  ·  2018

Pulmonary hypertension is a common clinical disease, with complex etiology, rapid progression, and high mortality and disability rate. At present, domestic and foreign guidelines divide pulmonary hypertension into five categories, of which the first category is called arterial pulmonary hypertension (PAH). In recent 20 years, with the in-depth research on the pathogenesis of pulmonary hypertension, targeted therapeutic drugs targeting the pathogenesis of PAH have been widely used in clinical practice. However, although these targeted drugs effectively improve cardiac function and quality of life in patients with PAH, PAH remains a progressive disease with poor prognosis^[1]。

In the 20th century, many people died of infectious diseases at a relatively young age, but in the 21st century, the death issue faced by people has changed dramatically because successful public health strategies and advanced medical technologies have significantly increased people's life expectancy. At the same time, these changes have changed attitudes towards death^[1]Going to the end of life with dignity has become the expectation of more people. Hospice care refers to the comprehensive services provided by the hospice team for critically ill patients and their families when medical measures for the purpose of cure cannot control the deterioration of the condition and the patient's expected life may be less than 6 months. In this paper, the end-of-life care for the elderly mainly refers to the comprehensive services specially provided for the dying elderly and their families over the age of 60^[2]。 The purpose of this paper is to explore the challenges and policy predicaments faced by the hospice service for the elderly from the perspective of diversified disciplines, and to face the limitations of traditional concepts, advocate the construction of a new view of life and death, combine macro system with micro practice, and discuss the countermeasures of hospice service for the elderly in depth.

Breast cancer is one of the most common malignancies in women. The incidence of female breast cancer in China is increasing year by year, with about 270,000 new patients every year^[1]Among them, 3% to 8% of breast cancer patients are metastatic at first diagnosis^[2]。 Even in early patients who have undergone surgery and standardized treatment, 30% to 40% will still relapse and metastasize^[3]。 Although advanced breast cancer is difficult to cure at present, it can alleviate the clinical symptoms of patients, improve the quality of life of patients, and further prolong the survival time of patients by developing new therapeutic drugs and optimizing treatment models.

Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis (HLH), is an immune-mediated life-threatening disease. HLH can affect people of all ages, not only in patients with congenital genetic susceptibility to immunodeficiency, but also in an increasing number of patients with autoimmune diseases, persistent infections, malignancies or immunosuppression, thus involving a multidisciplinary cross-section. In order to improve clinicians' knowledge and understanding of HLH and provide standardized clinical practice guidance, relevant experts at home and abroad demonstrated and extensively solicited opinions, and reached the following consensus on the diagnostic procedures, laboratory tests, diagnostic criteria and treatment principles of HLH.

To analyze clinical features, prognosis and treatment of lymphocytic hypophysitis (LYH).

The clinical data, treatments and outcomes of 18 cases diagnosed as LYH at Chinese PLA General Hospital between January 2001 and July 2017 was respectively reviewed.

Eighteen patients with histology-proven LYH (13 females and 5 males ) were identified. All lymphocytic adenohypophysitis (LAH) were females(n=6), two of whom were associated with pregnancy. Eleven patients (6 females and 5 males) had lymphocytic panhypophysitis (LPH) and one(female) had hypothalamitis. Pre-treatment evaluation revealed that 11 patients presented with symptoms of intracranial space-occupying lesions, 12 patients had symptoms of anterior pituitary hormone deficiencies, and 12 patients had central diabetes insipidus (CDI). All patients had space-occupying lesions on magnetic resonance imaging (MRI), which were symmetrically enlarged and homogenously enhanced with or without pituitary stalk thickening. Before or after surgery, 11 patients received immunosuppressant therapy or radiotherapy to alleviate space-occupying effect. After 4-204 months follow-up, 5 patients had a relapse and received immunosuppressants, radiotherapy or surgery to achieve remission. Full recovery (both symptomatic and radiographic) was seen in 6 patients, and 11 patients maintained stable replacement therapy.

LYH presents with acute space-occupying effects such as headache, visual disturbances, hypopituitarism, CDI and mild hyperprolactinemia, especially with characteristic radiographic manifestations. Usually, surgery reliably establishes diagnosis, and immunosuppressant therapy is a necessity. On the whole, LYH has a good prognosis.

To investigate and compare the effect and safety of nasal high-flow oxygen therapy (HFNCO) and noninvasive ventilation (NIV) therapy after extubation in patients with chronic obstructive pulmonary disease (COPD).

All COPD patients subjected to mechanical ventilation in the Emergency Intensive Unit of the First Affiliated Hospital of Zhejiang University during January 2015 to June 2016 were included in the study. The patients were divided into two groups after extubation and HFNCO and NIV were adopted on each group respectively. Clinical indexes including the patients′ general condition, blood gas analysis and pulmonary function before and after extubation, ratio of re-intubation and CT grades were collected and analyzed.

There was no significant difference in the incidence of aspiration (4.8% vs 8.3%), pressure sores (0 vs 8.3%) and delirium (4.8% vs 12.5%) between the two groups (all P>0.05). At 12 h after extubation, the oxygenation index of NIV group was significantly higher than that of the HFNCO group (265±29 vs 297±33;P<0.05), while no significant difference in PCO₂ (P>0.05). For 24 h and 72 h after extubation, there was no statistically significant difference in oxygenation index and PCO₂ between the both groups (P>0.05). The intensive care unit (ICU) retention time in HFNCO group was significantly lower than that in NIV group (13.7±0.8 vs 15.2±0.5;P<0.05). In addition, no significant difference between the two groups in mortality and re-intubation rate at 28 d (P>0.05) was observed.

HFNCO is effective and safe in the treatment of COPD patients after extubation, and it is hence valuable for further clinical application.

To compare the efficacy of percutaneous endoscopic transforaminal discectomy (PTED) and transforaminal lumbar interbody fusion (TLIF) in the treatment of high lumbar disc herniation.

The clinical data of patients with high lumbar disc herniation from February 2010 to February 2015 were retrospective analyzed. According to the inclusion criteria, a total of 63 cases were enrolled, including PTED group 33 cases, TLIF group 30 cases. The improvement of the two groups before and after surgery was assessed by visual analogue scale (VAS) and Oswestry dysfunction index (ODI). The operative time, intraoperative blood loss, drainage volume at 48 h postoperatively, hospitalization time, number of fluoroscopy, complication, recurrence rate and postoperative recovery were compared between the two groups. The follow-up period was 12 to 33 months.

The operation time, intraoperative blood loss, drainage amount and hospitalization time in PTED group were significantly less than those in TLIF group[(71±19) vs (121±22) min, (30±21) vs (317±50) ml, 0 vs (93±29) ml, (3.5±1.9) vs (12.5±2.1) d]. The number of fluoroscopy in PTED group was significantly higher than TLIF group[(16.2±8.3) vs (6.7±4.2)](allP<0.05). There was no significant difference in VAS score and ODI improvement rate between the two groups after operation (bothP>0.05). There was no significant difference between the two groups in the excellent rate of surgery and the recurrence rate (bothP>0.05).

PTED has the advantages of less trauma and bleeding, rapid postoperative recovery in the treatment of upper lumbar disc herniation compared with TLIF, and the curative effect and recurrence rate are similar with TLIF. Therefore, PTED is an effective method for the treatment of upper lumbar disc herniation.

To analyze the genotype-phenotype correlations among those thalassemia samples with the presence of -α^3.7, --^SEA and normal α ₂ alleles on their α-globin gene clusters.

Fourteen patients(including 1fetus, 4 males and 9 females, aged 0- 56 years old)who were suspected diagnosed by hematologic analysis and genetic testing among 16 080 participants in our laboratory since from August 2011 to August 2016, were enrolled. Complete blood cell count was performed on XE4000i automatic hemocyte analyzer. HbA0, HbF and HbA2 were tested by high performance liquid chromatography (HPLC). Gap-PCR was adopted to detect three common deletional thalassemia deletions. Reverse dot-blot (RDB) assay was applied for detecting 17 common β-globin gene mutations and three common non-deletional α ₂ gene mutations. Two-round nested PCR assay was established to detect the genotype of HKαα in α-thalassemia.

Fourteen cases were identified as HKαα/--^SEA (14/16 080), including a pedigree and a rare case of HKαα/--^SEA co-inheritance with IVS-Ⅱ-654(C→T) heterozygote. In HKαα/--^SEA thalassemia group, mean cell volume(MCV) was (69.54±5.92)fl, and mean cell hemoglobin(MCH) was(22.11±2.22)pg and hemoglobin(Hb) was (117.64±18.14) g/L. Compared with normal group, MCV, MCH and Hb in HKαα/--^SEA thalassemia group, was significantly decreased(P<0.05). There were no significant differences between α-thalassemia control group(--^SEA /αα) in most hematological parameters (P>0.05).

The two-round nested PCR could effectively detect the HKαα/--^SEA genotype. The hematologic characteristics changed significantly in HKαα/--^SEA group compared with HbH thalassemia and normal group. The genotype and phenotype non-correlation in patients with α-thalassemia should especially be causious to avoid a misdiagnosis of genetic tests, especially in prenatal diagnosis.

To study the in vitro activity of fosfomycin to extended-spectrum β-lactamases (ESBLs)-producing Escherichia coli and Klebsiella pneumoniae and to explore the mechanisms of fosfomycin resistance.

A total of 1 052 ESBLs-producing E. coli(ESBL-EC) and K. pneumoniae(ESBL-KP) isolates were collected from bloodstream infections of 28 hospitals of 22 provinces and municipalities, which were stored by our laboratory.Minimum inhibitory concentrations (MICs) of fosfomycin against these clinical isolates were determined by agar dilution methods according to the Clinical and Laboratory Standards Institute (CLSI)(2015). The genes related to fosfomycin resistance were confirmed by Polymerase Chain Reaction (PCR) and sequencing.

The susceptibility rates of ESBL-EC and ESBL-KP isolates to fosfomycin were 91.3% (818/896) and 91.7% (143/156), respectively. A total of 91 fosfomycin-non-susceptible isolates were detected, of which 73 (80.2%) isolates carried fosA3 genes.Amongst 18 fosA3-negative isolates, 16 isolates were detected to have chromosomal mutations or insertion inactivation, while the rest two isolates had not been detected any resistant mechanisms.

Fosfomycin shows great in vitro antimicrobial activity to ESBL-EC and ESBL-KP. The primary mechanism of fosfomycin-non-susceptible isolates is fosA3 gene.Chromosomal mutations may also involve in the fosfomycin resistance.

To explore the value of albumin-bilirubin (ALBI) grade combined with serum ammonia in the diagnosis of cirrhosis with hepatic encephalopathy (HE).

The serum level of total bilirubin(TBIL), albumin( ALB )and blood ammonia were detected in 139 patients including 73 cirrhosis patients without HE and 66 cirrhosis patients with HE from January 2015 to January 2017 in Beijing You′an Hospital, and the relationship between ALBI and blood ammonia value and Child grade and hepatic encephalopathy was analyzed.

The level of ALBI and blood ammonia were more and more higher with the increase of Child grade, the level of ALBI in Child A, B and C were -2.3±0.6, -1.7±0.5, -0.9±0.4, and there was a statistically significant(F=125.100, P<0.001). The blood ammonia concentration in Child A, B and C were(42.6±16.0), (56.1±31.2), (69.8±34.7) μmol/L, and there was a statistically significant(F=7.400, P<0.001). The level of ALBI was higher with the increase of model for end-stage liver disease (MELD) grade, and there was a positive correlation(r=0.547, P<0.001). The ALBI value in the HE group was higher than the cirrhosis patients without HE((-1.1±0.5)vs(-1.6±0.7)), and the difference was statistically significant (t=5.244, P<0.001). Level of blood ammonia in the HE group was(83.6±39.5)μmol/L, which was higher than the level of cirrhosis patients without HE(42.9±17.0)μmol/L, and the difference was statistically significant (t=8.130, P<0.001) . When ALBI and blood ammonia were combined, the ROC curve area was 0.911, the sensitivity was 93.9%, the specificity was 93.2%.

There is a significant diagnosis value and high clinical application when ALBI is combined with blood ammonia to diagnose HE .

To develop a predictive nomogram based on multi-parametric magnetic resonance imaging (mpMRI) information to identify men more likely to have a cancer diagnosed on repeat prostate biopsy.

The clinical data of 237 patients who received repeat prostate biopsy after initial negative biopsy from Department of Urology of Peking University First Hospital between January 2001 and August 2016 was reviewed. Patient age, body mass index (BMI), serum total prostate-specific antigen (PSA), percent free PSA (f/t), prostate volume (PV), PSA density (PSAD), PSA velocity (PSAV), digital rectal examination (DRE), transrectal ultrasound (TRUS)and mpMRI results were included in the univariate and multivariate analysis. A nomogram was developed using selected variables and the area under the receiver operating characteristic (ROC) curve was calculated as a measure of discrimination.

A total of 76 patients (32.07%) had prostate cancer (PCa) detected on repeat biopsy. Based on univariate and multivariate logistic regression analysis, the patient age, PSA, PV, DRE and mpMRI results were independent predictors for the diagnosis of PCa on repeat biopsy. The current nomogram performed well (AUC=0.910) and showed excellent calibration.

Multi-parametric magnetic resonance imaging combined with age, PSA, PV and DRE can predict the probability of PCa in patients with initial negative biopsy. The nomogram might help in decision-making for men with prior benign histology before the performance of repeat biopsy.

To study the incidence, clinical characteristics, and prognostic impact of acute kidney injury (AKI) in very elderly patients.

The very elderly patients (≥75 years) from the Geriatric Department of the Chinese PLA General Hospital between January 2007 and December 2015 were retrospectively enrolled. AKI was defined according to the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria. AKI patients were divided into survivor group and non-survivor group by their outcomes within 90 days after AKI. Prognostic survival factors were identified using the Cox proportional hazards regression model.

In total, 668 geriatric patients (39.0%) developed AKI, and 652 patients were included in the final analysis. The median age of the cohort was 87 (84-91) years, the majority (623 cases, 95.6%) of whom were male. Among these 652 patients, 308 (47.2%) had AKI stage 1, 164 (25.2%) had AKI stage 2, and 180 (27.6%) had AKI stage 3. Of the 652 AKI patients, the 90-day mortality was 33.6% (219/652). Multivariate analysis by the Cox model revealed that persistent AKI (HR=5.741, 95% CI: 3.356-9.822, P<0.001), more severe AKI stage (stage 2:HR=3.363, 95% CI: 1.973-5.732, P<0.001 and stage 3:HR=4.741, 95% CI: 2.807-8.008, P<0.001), high blood urea nitrogen (BUN) level (HR=1.025, 95% CI: 1.014-1.037, P<0.001), low body mass index (HR=0.939, 95% CI: 0.897-0.984, P=0.008), low mean arterial pressure (MAP) (HR=0.969, 95% CI: 0.959-0.979, P<0.001), low prealbumin level (HR=0.935, 95% CI: 0.911-0.959, P<0.001), infection (HR=1.410, 95% CI: 1.055-1.884, P=0.020), oliguria (HR=1.948, 95% CI: 1.266-2.998, P=0.002) were associated with 90-day mortality.

The incidence of AKI increases significantly with advanced age. More frequent serum creatinine (SCr) measurements may be helpful for the early diagnosis of geriatric AKI. Identification of risk factors might promote more intensive monitoring and early prevention, and thus improve outcomes for very elderly patients with AKI.

To explore the effect of picroside Ⅱ on the expression of mitochondrial voltage-dependent anion channel 1 (VDAC1) in rats after cerebral ischemiareperfusion.

A total of 70 Wistar rats models with middle cerebral artery occlusionreperfusion (MCAO/R) were randomly divided into the sham group, model group, picroside (Picr) group, ruthenium red (RuR) group, RuR+ Picr group, Spermine (Sper) group, Sper+ Picr group (n=10 per group). Modified neurological severity scale (mNSS) was used to evaluated the neurobehavioral function, the expression of reactive oxygen species (ROS) in brain tissues were measured by enzyme-linked immunosorbent assay (ELISA), the morphology of brain tissues was observed by hematoxylin-eosin (HE) staining, the apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL), and the expressions of VDAC1 and endonuclease G (EndoG) were determined by immunohistochemical assay and Western blot.

Compared with the shame group, the mNSS scores (9.6±1.9), the expression of ROS[(47.6±2.7)U/ml], the apoptosis of neuron(23.8±2.8), and the expressions of VDAC1(0.94±0.06) and EndoG in cytoplasm (0.76±0.06) and nuclei(0.75±0.06)were enhanced in the model group (all P<0.05). The Picr group had obviously decreased mNSS scores (5.7±0.9), ROS expression[(35.6±2.2)U/ml], number of apoptotic cells (14.5±2.1), VDAC1 (0.63±0.06) and EndoG in cytoplasm (0.34±0.05) and nuclei (0.31±0.06)expressions compared to the model group (P<0.05).

Picroside Ⅱ could attenuate cerebral I/R injury by down-regulating the expression of VDAC1 and inhibiting the EndoG release from mitochondria into cytoplasm.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a clinical syndrome that has plagued patients for a long time. At present, the diagnosis mostly follows the definition of urodynamic and female urology society: that is, an unpleasant sensation (including pain, pressure and discomfort) perceived to be associated with the bladder, which can be combined with lower urinary tract symptoms, and the course of the disease is more than 6 weeks, except for infection or other clear causes^[1]。 Because of the unknown etiology, variable symptoms and lack of specific diagnostic methods, the clinical diagnosis and treatment of IC/BPS are difficult. Patients with newly diagnosed IC/BPS at work were confirmed to have urothelial carcinoma of the bladder after a long period of diagnosis and treatment^[2,3,4,5]。 This study analyzed the clinical data of 412 patients newly diagnosed with IC/BPS in Peking Union Medical College Hospital from January 2005 to December 2015. Among them, 3 patients were diagnosed with bladder urothelial carcinoma 16, 27 and 19 months after the diagnosis of IC/BPS, respectively. The diagnosis and treatment results are reported as follows.

Allergic bronchopulmonary aspergillosis (ABPA) is an immune-mediated lung disease mainly caused by the body's allergy to Aspergillus fumigatus^[1]； It mainly occurs in patients with bronchial asthma (asthma for short) and pulmonary cystic fibrosis, and can also occur in patients with chronic obstructive pulmonary disease^[2]。 The disease often manifests as migratory or recurrent pulmonary infiltrates, including bronchiectasis, mucous plug impaction, tree bud sign and small nodules^[3]Pulmonary fibrosis may occur in the later stage. Common forms of airway mucous impaction include double track sign, finger cuff sign and toothpaste sign^[4]。 Carcinoembryonic antigen (CEA) is usually a marker of malignant tumors. Clinically, some patients with ABPA show abnormal chest CT occupation and elevated serum CEA, which is difficult to distinguish from lung malignant tumors. The clinical data of 7 patients with ABPA and increased serum CEA are retrospectively analyzed as follows.

With the extensive development of anterior cervical fusion surgery and the development of techniques to preserve motor segment function, adjacent segment disease (ASD) after cervical fusion has received more and more attention. ASD refers to new radiculopathy or myelopathy in adjacent active segments after anterior cervical fusion; Simply imaging degenerative changes of adjacent segments such as disc degeneration, osteophyte formation, articular process hyperplasia and spinal canal stenosis without clinical symptoms are called cervical adjacent segment degeneration^[1]。 Studies have shown that the incidence of adjacent segment degeneration after cervical fusion is 50%-92%, while the incidence of ASD is 6.1%-16.9%^[2]。 The short-term effects of 12 patients with ASD treated with zero-notch intervertebral cage (Zero-P) are retrospectively analyzed as follows.

Epithelioid hemangioendothelioma (EHE) is a rare, low-grade malignant tumor of vascular origin. It mostly occurs in soft tissues and organs such as lungs, bones, brain and small intestine^[1]。 EHE originating from the liver is less, mainly affecting adults (30-40 years old), more common in women and rare in children. The clinical manifestations and imaging examinations were not specific, and histologically they were easily confused with hepatocellular or intrahepatic bile duct epithelial malignancies. This paper reports a case of liver EHE diagnosed by puncture biopsy. Combined with relevant literatures, the clinical manifestations, pathological changes and differential diagnosis of this disease are comprehensively analyzed and summarized, so as to improve the understanding of this disease.

Case 1, male, 71 years old, with primary myelofibrosis (PMF) for more than 5 years and blood in sputum for 1 day, was admitted to hospital with "acute myeloid leukemia" on April 24, 2017. The patient was examined in January 2012 due to splenomegaly (200 mm ×59 mm) with hemogram abnormalities: white blood cells (WBC): 15.86×10⁹/L, hemoglobin (Hb): 117 g/L, platelets (PLT): 560×10⁹/L, PMF was confirmed by bone marrow smear and bone marrow biopsy, reticular fiber staining + + + +, and JAK2V617F mutation was positive. Hydroxyurea, thalidomide, calcitriol and interferon were given, and the condition was stable. March 2015 Abdominal distension with asthenia, Hb: 83 g/L, WBC: 2.71×10⁹/L, PLT: 203×10⁹/L, blood smear: original granule 22%, bone marrow dry draw, progression to acute myeloid leukemia, recommended chemotherapy, family refused. After that, severe abdominal distension, lower extremity edema, severe anemia, Hb fluctuating between 50 and 58 g/L, requiring monthly blood transfusion, each transfusion of 6 to 8 U red blood cells. Signed an informed consent form with the patient and started oral administration of rapamycin target protein (mTOR) inhibitor sirolimus capsules 0.5 mg/d in August 2015. In October 2015, the blood routine was improved compared with the previous, Hb: 66 g/L, WBC: 5.56×10⁹/L, neutrophils 41.7%, PLT 344×10⁹/L, the transfusion interval was lengthened to 2 months. After January 2016, the blood transfusion was withdrawn, the spleen was reduced, the abdominal distension was reduced, and there was no edema in the lower limbs. Abdominal ultrasound in February 2016: spleen 171 mm ×60 mm, in May 2016, blood routine was reviewed, Hb: 79 g/L, WBC: 25.38×10⁹/L, PLT: 214×10⁹/L, because the anemia was reduced but the white blood cells rose, the dose of sirolimus was increased to 1 mg/d, and the condition continued to improve, Hb: 75~88 g/L, WBC: 20×10⁹/L for 16 months. In January 2017, the patient's condition progressed, the anemia worsened, and he received another blood transfusion. He came to the hospital with blood in the sputum 1 day before this admission. Blood routine : Hb: 59 g/L, WBC: 110×10⁹/L, PLT: 30×10⁹/L, 64% of blood smear particles. Physical examination: anemic appearance, giant spleen, peripheral blood flow test: 70% of the original granule, JAK2V617F mutation still positive, MPL mutation negative, CALR mutation negative, acute myeloid leukemia diagnosed, PMF conversion, chemotherapy recommended, family refused, treatment abandoned.

Clostridium difficile is a gram-positive, toxin-producing or non-toxin-producing anaerobic bacillus. The bacteria spread mainly through the fecal-oral route, and the symptoms of infection ranged from mild diarrhea to life-threatening pseudomembranous colitis. The overall mortality rate was 6%, rising to 13.5% in elderly patients^[1]。 Clostridium difficile spores are highly resistant to disinfectants such as ethanol, soap, heat, and dryness, and can survive on the surface of objects for months to years, facilitating their spread. It is generally believed that Clostridium difficile infection (CDI) is related to the use of antimicrobial drugs and the history of hospitalization, and the use of antimicrobial drugs can lead to eosinopenia, which is the main risk factor of CDI^[2]。 However, some patients with CDI were not associated with a recent history of exposure to antimicrobial drugs, while the use of proton pump inhibitors and dyskinesia could induce microbiological dysbiosis and lead to CDI^[3,4]。 Thanks to a boost from the Human Microbiology Project and the European Human Gut Metagenome Project (MetaHIT), many experts have studied the relationship between human health and disease and the microbiome, focusing in particular on the study of metabolic activity that maintains and resists the gut microbiome colonized by C. difficile, and how antimicrobial drugs can alter the gut microbiome leading to C. difficile susceptibility. In this paper, the relationship between CDI and intestinal microbiota is discussed, and the mechanism of CDI infection and the latest prevention and treatment scheme are discussed from the perspective of metabolism, so as to discover new therapeutic targets.