Volume 98  ·  Issue 04  ·  2018

Chronic obstructive pulmonary disease (COPD for short) is one of the important chronic non-communicable diseases in China and even the world. It keeps pace with hypertension, coronary heart disease and diabetes, and ranks at the forefront of diseases with great harm to social and economic burden. The prevalence rate of people ≥40 years old in China is 8.2%^[1]It is estimated that the number of COPD patients in China is over 40 million, and due to the combined or separate effects of many factors, such as the presence of a large number of smokers, the large exposure of biofuels in rural and remote areas, and the long-term persistence of air pollution, it is predicted that the prevalence of COPD will further increase for a long time in the future. Therefore, we should actively respond to this disease that seriously endangers people's health, scientific understanding, early detection and early prevention. At the same time, we should actively develop therapeutic drugs targeting new targets and new mechanisms, as well as explore and develop new uses of drugs that have been marketed, especially to develop methods and drugs that are suitable for China's national conditions for the treatment of COPD, which are effective, safe, cheap and convenient to use.

Endocrine therapy is the main means of adjuvant and advanced treatment of hormone receptor (HR) positive breast cancer. In recent decades, endocrine therapy drugs have been continuously innovating and developing, from the earliest selective estrogen receptor modulator (SERM) drug therapy to the establishment of aromatase inhibitor (AI) era to the arrival of AI + era, the treatment model has been changing^[1]。 This article will elaborate on the progress of endocrine therapy in postmenopausal breast cancer in combination with the latest drug development and clinical research.

Chronic obstructive pulmonary disease (COPD) is an important global public health problem because of its high morbidity and mortality, great harm and heavy burden. COPD currently occupies the fourth most common cause of death in the world, and is expected to rise to the third place by 2020, and the economic burden accounts for the fifth place among all diseases^[1]。 The prevalence of COPD among people ≥40 years old in China is as high as 8.2%^[2]。 Therefore, scientific understanding, early detection, early prevention and effective, economical and standardized drug treatment are a significant and difficult challenge in clinical practice.

To construct a dynamic enhanced MR based predictive model for early assessing pathological complete response (pCR) to neoadjuvant therapy in breast cancer, and to evaluate the clinical benefit of the model by using decision curve.

From December 2005 to December 2007, 170 patients with breast cancer treated with neoadjuvant therapy were identified and their MR images before neoadjuvant therapy and at the end of the first cycle of neoadjuvant therapy were collected. Logistic regression model was used to detect independent factors for predicting pCR and construct the predictive model accordingly, then receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive model.

ΔArea_max and Δslope _max were independent predictive factors for pCR, OR=0.942 (95%CI: 0.918-0.967) and 0.961 (95%CI: 0.940-0.987), respectively. The area under ROC curve (AUC) for the constructed model was 0.886 (95%CI: 0.820-0.951). Decision curve showed that in the range of the threshold probability above 0.4, the predictive model presented increased net benefit as the threshold probability increased.

The constructed predictive model for pCR is of potential clinical value, with an AUC>0.85. Meanwhile, decision curve analysis indicates the constructed predictive model has net benefit from 3 to 8 percent in the likely range of probability threshold from 80% to 90%.

To explore the expression of latent transforming growth factor (TGF)-beta binding protein 2 (LTBP2) in breast cancer and its clinical significance.

Immunohistochemistry was used to detect the expression of LTBP2 in 125 cases of breast cancer tissue and normal breast tissue. Relationship between the expression of LTBP2 and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, and its relationship with clinicopathological parameters of breast cancer were analyzed.

The positive expression of LTBP2 in breast cancer tissues (55.20%) was significantly higher than that in adjacent normal breast tissues (28.80%) (P<0.001). The expression of LTBP2 in breast cancer tissues was correlated with the clinical stage (χ²=4.516, P=0.034), over-expression of ER (χ²=7.112, P=0.008) and Ki67(χ²=4.024, P=0.045) and other adverse prognostic factors.

Positive expression of LTBP2 in breast cancer plays an important role in the development and progression of breast cancer, and may be a marker of prognosis of patients.

To explore the effect of hypoxia inducible factor (HIF)-2α on biological characteristics of breast cancer stem cells (BCSCs).

Stem cells were isolated and purified from MCF-7 cells by using the immunomagnetic microbeads. HIF-2α ORF/shRNA lentiviral vectors were transduced into MCF-7 stem cells respectively, and then the stable stem cell lines were detected and gained. Using the method of Cell Counting Kit-8 (CCK-8) and flow cytometry, the effect of HIF-2α on cell vitality and apoptosis of MCF-7 cancer stem cells (CSCs) were tested. Serum-free suspension culture was used on MCF-7 cells to get breast CSCs microspheres. The expression of CD44⁺ in different groups were detected by flow cytometry. Tumor-bearing nude mice model was established to compare tumor growth rate and pulmonary metastasis probability of MCF-7 CSC HIF-2α knock up/downin vivo.

Compared with MCF-7 CSC group, the apoptosis rate of MCF-7 CSCs HIF-2α knockup group decreased obviously and cell proliferation activity increased significantly (allP<0.05). However, the MCF-7 CSCs HIF-2α knock down group had the opposite trend. Results of flow cytometry showed that the proportion of CD44⁺ cells in HIF-2α knock up group(93.0%)was much higher than MCF-7 group(83.8%)and MCF-7 HIF-2α knock down group(51.6%). The tumor growth rate, quality and lung metastasis rate of MCF-7 CSC HIF-2α knock up group were significantly higher than those in MCF-7 CSCs group and MCF-7 CSCs HIF-2α knock down group (P<0.01).

In hypoxic microenvironment, up-regulation of HIF-2αpromoted the formation of MCF-7 CSCs. Over-expression of HIF-2α can promote proliferation and inhibit apoptosis of MCF-7 CSCs, and thus increase the risk of tumorigenic ablility and pulmonary metastasis.

To explore the prognosis and its risk factors in anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) patients who needed initial renal replacement therapy (RRT).

One hundred patients [54 females, 46 males, with a median age of 54(41, 60) years] with biopsy-proven AAGN and requiring initial RRT between January 1996 and December 2016 in Nanjing Jinling Hospital were included. Intensive immunotherapy indicated that the patients received corticosteroids in combination with cyclophosphamide or mycophenolate mofetil, or immunoadsorption (IA) or double filtration plasmapheresis (DFPP). The clinical and histological risk factors for renal survival were analyzed.

Forty-one patients were free of RRT after a median time of 1 (0.5, 2) month treatment (dialysis-independent group), and the remaining 59 patients were on maintenance dialysis (dialysis-dependent group). The multivariate logistic analysis revealed that the proportion of normal glomeruli <8% ( OR=5.95, P=0.002) and global sclerotic glomeruli ≥50% (OR=4.87, P=0.003), and not receiving intensive immunotherapy (OR=7.81, P=0.004) were the risk factors for the renal recovery in these patients. During a median follow-up time of 22 (10, 50) months, 15 patients(36.6%) in the dialysis-independent group progressed into maintenance dialysis, and the 1 and 3 year renal survival rate were 86% and 60%, respectively. During a median follow-up time of 6 (2, 24) months, 12 (12%) patients died, among whom four patients died of therapy. The multivariate Cox regression analysis revealed that IA/DFPP treatment (HR=10.85, P=0.034) and low albumin level (HR=1.26, P=0.009) significantly associated with a higher risk of therapy-related death.

The renal recovery rate in AAGN patients with initial RRT was low. The proportion of normal and global sclerotic glomeruli, receiving intensive immunotherapy or not were associated with renal outcome, and IA/DFPP treatment as well as lower albumin level were independently associated with therapy-related death.

To summarize the clinical characteristics of paraganglioma.

A total of 215 pheochromocytoma/ paraganglioma cases in Peking University First Hospital between January 1996 and December 2014 were retrospectively analyzed. The patients were divided into two groups according to the tumor position: pheochromacytoma group (173 patients) and paraganglioma group (42 patients). Then the clinical characteristics between the groups were compared.

There were 42 paraganglioma cases in the study, accounting for 19.5%. The most common position was retroperitoneum (66.7%, 28/42), followed by bladder (19.0%, 8/42), para-aorta (11.9%, 5/42) and pelvic cavity (2.4%, 1/42). Sixty-nine percent (29/42) of patients had different degree of hypertension, while up to 31.0% (13/42) was silent type. There was no statistical difference between the two groups in severity of hypertension, age, gender, duration, abnormal glucose metabolism, and the incidence of hypokalemia( all P>0.05). Adrenaline level was higher in pheochromocytoma group (13.4% vs 9.5%,P=0.004), while noradrenaline level was higher in paraganglioma group (80.8% vs 59.2%, P=0.001). Malignancy (21.4% vs 4.6%, P<0.001) and bigger tumor size [(6.67±3.24)cm vs (5.55±2.76)cm,P=0.024] was more common in paraganglioma group. The maximum tumor volume was 18.0 cm×18.0 cm×10.5 cm vs 14.0 cm×13.0 cm×7.0 cm, while the minimum was 1.8 cm×1.3 cm×1.3 cm vs 1.2 cm×1.0 cm×1.0 cm. There was no significant difference in the pathological manifestations between the two groups. In the study, 11.9% (5/42) of patients in paraganglioma group was misdiagnosed or indefinite at the early diagnosis.

Compared with pheochromocytoma, paraganglioma has the characteristics of widely distribution, more various clinical performance, more silent type and higher malignant rate. It is critical to put emphasis on its early diagnosis and treatment.

To analyze the clinical manifestations, therapeutic efficacy, prognosis and characteristics of NPC1 mutation in Chinese patients with Niemann-Pick disease type C(NPC).

Ten unrelated Chinese NPC patients were diagnosed by NPC1 mutation analysis from July 2013 to February 2017 in Beijing Tian Tan Hospital of Capital Medical University. Clinical data of 10 cases were analyzed retrospectively which included clinical manifestations, laboratory results and NPC1 gene mutation features, and a series of follow-up were carried out about therapeutic efficacy and prognosis.

Ten patients suffering from NPC included 5 males and 5 females, aged from 42 days to 14 years when they presented to Tian Tan Hospital. According to their age of neurological onset, 4 were in early infantile period, 2 in late infantile period, 2 in juvenile periods, and the other 2 cases in neonatal period. They all presented with splenomegaly, 5 of 10 accompanied with hepatomegaly. Two cases of neonatal subtype presented mainly with delayed neonatal cholestatic jaundice and hepatosplenomegaly, accompanied with decreased muscle tone and slight psychomotor retardation. The other 8 cases presented with severe neurological involvement, such as progressive encephalopathy, ataxia and language impairment, 4 with dystonia, 3 with decreased muscle tension, 5 with vertical supranuclear gaze palsy, 5 with gelastic cataplexy, and 4 with epilepsy. Eight of 9 cases presented with foam cells in their bone marrow. Head MRI showed diffuse cerebral atrophy in 8 cases, thin corpus callosum in 2 cases, and brain white matter abnormal signals in 2 cases. Among 10 cases, 18 different mutations of NPC1 allelic genes were identified including 11 reported mutations, 3 novel missense mutations: c. 3683T>C (p.Met1128Thr), c.1926G>C (p.Met642Iie) and c. 3006C>G (p.Phe1002Leu), 2 novel nonsense mutation: c. 1142G>A(p.Trp381Ter ) and c. 3229C>T(p.Arg1077Ter), 1 novel minimal deletion mutation: c. 1385-1386del, and 1 novel intron mutation: c. 1757+ 5G>A. In 5 cases, the symptom of gelastic cataplexy was alleviated by imipramine, and the convulsion was relieved by valproate in 2 cases, by carbamazepine in 1 case at the beginning of seizure. During the 25 (3-66) months of follow-up, 4 cases died, the others′ neurological symptoms were deteriorated progressively.

The NPC1 gene mutation were high heterozygous in this group, and 7 novel mutations enriched the gene mutation spectrum of NPC1. The neurological manifestations were complicated in patients with NPC, and the symptomatology would be different according to their onset age of neurological symptoms. There might be effective symptomatic treatment for gelastic cataplexy by imipramine and for convulsion by valproate or carbamazepine.

To investigate the relationship between C-C chemokine receptor type 2(CCR2) and P38 mitogen-activated protein kinase (P38MAPK) signaling pathway in the spinal cord of rats and further clarify the mechanism of bone cancer pain (BCP).

A total of 92 healthy female SD rats, of which 60 were subjected to behavioral tests using a ciliary mechanical stimulation needle. SD rats were randomly divided into six groups: sham operation group (group S), bone cancer pain group (group B), sham operation + DMSO solvent group (group SD), bone cancer pain + DMSO solvent group (group BD), sham operation + RS102895 CCR2 inhibitor group (group SR), bone cancer pain + RS102895 CCR2 inhibitor group (group BR), and Von Frey was used in the behavioral test. Another 32 SD rats were randomly divided into the following 8 groups (n=4): sham operation group (group S), bone cancer pain 5 d group (group B5), bone cancer pain 9 d group (group B9), bone cancer pain 14 d group (group B14), bone cancer pain + DMSO solvent group (group BD), bone cancer pain + RS102895 CCR2 inhibitor 0.5 h group (group BR0.5 h), bone cancer pain + RS102895 CCR2 inhibitor 4 h group (group BR4 h), bone cancer pain + RS102895 CCR2 inhibitor 12 h group (group BR12 h). Western blot was used to detect the expression of P38, p-P38 and CCR2 in spinal cord of rats.

At day 5, 7, 9, 14, 21 post-injection, mechanical withdrawal thresholds of group S were(30.9±1.5), (31.9±1.2), (32.0±1.1), (31.6±1.5), (32.2±1.4)g respectively, the mechanical withdrawal thresholds of group B were( 26.4±0.7), (24.4±0.8), (21.4±0.8), (13.5±0.4), (9.9±0.2)g respectively, the mechanical withdrawal thresholds in group B decreased obviously versus group S, and the differences were statistically significant(t=-13.177, -16.660, -23.778, -35.574, -48.401, all P<0.01). At day 9 post-injection, the mechanical withdrawal thresholds in SD, BD, SR and BR groups were (32.4±1.7), (19.4±1.1), (32.1±1.3), (26.3±1.0) g respectively, the difference was statistically significant (F=224.681, P<0.01), and the mechanical withdrawal thresholds in group BD decreased obviously versus group SD, while the mechanical withdrawal thresholds in group BR increased obviously versus group BD. The expression levels of p-P38 in spinal cord of group S, group B5, group B9 and group B14 were(0.08±0.03), (0.20±0.05), (0.40±0.17), (0.65±0.14)respectively, the expression levels of CCR2 were(0.08±0.04), (0.18±0.05), (0.30±0.09), (0.58±0.07)respectively, the difference was statistically significant(F=19.123, 40.746, all P<0.01), and the expression of p-P38 and CCR2 in group B9 were showed a significant up-regulation versus group S. The expression levels of p-P38 in spinal cord of group BD, group BR0.5 h, group BR4 h and group BR12 h were (0.57±0.06), (0.17±0.11), (0.03±0.01), (0.25±0.11)respectively, and the difference was statistically significant(F=29.582, P<0.01). The expression of p-P38 in group BR0.5 h, BR4 h, BR12 h showed a significant down-regulation versus group BD.

CCR2 in the spinal cord may be involved in the development of bone cancer pain by activating P38MAPK signaling pathway in rats.

To investigate the destruction of the mature biofilm and the inhibitory effect of the biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) by different concentrations of the innate defense regulatory peptide (IDR-1018).

1 ×10⁵CFU /ml MRSA was inoculated uniformly into 96 well plates, the biofilm model would be completed after 48 h. Given the different concentration of IDR-1018 solution as the experimental group double diluted with tryptic soy broth (TSB), the concentration in bacteria suspension reached 3.75-1 000 mg/L respectively. Erythromycin is double diluted into different concentration gradient, combined with low concentration (15 mg/L) of IDR-1018 as the mixed group.The same amount of TSB treated as the blank control group. The growth of the biofilm was measured through the measurement of the value of absorbance (A)by the semi-quantitative method of crystal violet staining at 24 h. Using SPSS 18.0 as statistical software to analyze the data.

Compared with the control group (A₅₉₅=1.764 ± 0.026), IDR-1018 significantly damaged the mature MRSA biofilm, and function was worked in a dose-dependent method. With decreasing drug concentration, the destruction of the biofilm decreased correspondingly. When the concentration was as low as 15 mg/L, A₅₉₅ = 0.946 ± 0.047(t=32.955, P<0.01). When the concentration was 7.5 mg/L,A₅₉₅ = 1.211±0.054 (t=12.731, P<0.05). When the concentration was 3.75 mg/L,A₅₉₅=1.360±0.066(t=4.843, P<0.05), the difference was still statistically significant compared with the control group. For the immature biofilm, compared with the control group(A₅₉₅=1.689±0.068), IDR-1018 still had a significant inhibitory effect on the formation process of MRSA biofilm when the concentration was as low as 15 mg/L (A₅₉₅=0.846±0.057, t=34.127, P<0.01). The inhibition of biofilm had a certain decline, when the concentration was 7.5 mg/L (A₅₉₅=1.402 ± 0.181, t=5.240, P<0.05). But the difference was still statistically significant compared with the control group. However, the inhibitory effect was significantly decreased when the concentration was 3.75 mg/L (A₅₉₅=1.631±0.190, t=0.913, P>0.05). When the low concentration (15 mg/L) of IDR-1018 and different concentrations of erythromycin were used together, the destruction and inhibition of MRSA biofilm was significantly higher than using erythromycin or IDR-1018 alone.

IDR-1018 can play a good inhibitory role in the formation process of MRSA biofilm, and can play a good role in destroying MRSA biofilm.

Cockett syndrome is the left iliac vein is compressed by the right iliac artery across its front and the long-term pushing of the fifth lumbar vertebra behind, causing intravascular proliferation, adhesion, fibrous band formation, etc., resulting in vascular stenosis or even occlusion, resulting in increased venous pressure and return obstacle in the left lower limb, and easy to form deep vein thrombosis^[1,2,3]。 The treatment of iliac vein stenosis has been mentioned in the course of treatment of Cockett syndrome with deep vein thrombosis of lower limbs. In the past, considering that left iliac vein stenosis has the function of "natural filter", which can prevent large thrombosis from falling off, we first placed a catheter for thrombolysis, and then considered balloon dilation and stent placement after the thrombosis was dissolved. It was found that the thrombolysis time was long, and the iliofemoral vein thrombosis was difficult to dissolve, so patients often needed to place two stents. Then we tried to change the surgical methods. In the first stage, we used balloon to dilate the iliac vein and place a catheter for thrombolysis, and in the second stage, we considered stent placement to compare the clinical effects of the two different surgical methods.

A 59-year-old female was admitted to hospital on July 27, 2017 because of "enlarged hands and feet, facial changes for more than 3 years, and the saddle area was found to occupy space for 5 months". Since 2014, the patient has gradually developed enlarged hands and feet, thickened joints, thickened lips, and ugly face. The shoe size has increased from 36 to 38, and the weight has increased by about 5 kg. Not treated. During the physical examination in February 2017, magnetic resonance imaging (MRI) of the head showed "sellar area occupation", and the patient went to the Department of Neurosurgery of Peking Union Medical College Hospital in July 2017. Since the onset of the disease, the spirit, appetite and sleep are good. He had been hypertensive for more than 10 years, with the highest blood pressure of 170/110 mmHg (1 mmHg =0.133 kPa). He took 2.5 mg of "Shoubishan" daily, and his blood pressure was controlled at about 120/70 mmHg. The patient reported that the younger brother's face in the family had similar changes.

A 38-year-old female was admitted to the Department of Nephrology, Peking University People's Hospital on May 18, 2017 due to "intermittent edema and fatigue of both lower limbs for 3 years". Three years ago, the patient began to have concave edema of both lower limbs, fatigue, repeated lower limb twitching, bone pain, increased foam in urine, no deepening urine color, and increased nocturia without obvious trigger. After many visits to other hospitals, the laboratory tests showed a small amount of proteinuria, renal glycosuria, hypokalemia, hypophosphatemia, hypouricemia, metabolic acidosis, hypocalcemia, renal insufficiency, iron deficiency anemia, blood alkaline phosphatase increase, immunoglobulin M (IgM) increase, anti-mitochondrial antibody subtype M2 (AMA-M2) positive, and bone mineral density examination showed osteoporosis. After treatment with acid correction, calcium supplementation, anti-osteoporosis, potassium supplementation and urinary protein reduction, the bone pain improved, but other symptoms and laboratory indexes never returned to normal. After stopping the drug, the bone pain recurred, so we came to our hospital for further diagnosis and treatment. Since the onset of the disease, the patient has no dry mouth, dry eyes, no flaky tooth loss, rampant dental caries, no swelling of the parotid and lacrimal glands, no emaciation and night sweats.

Chronic obstructive pulmonary disease (COPD) is one of the chronic diseases with high morbidity and mortality in the world. It brings a heavy mental and economic burden to individuals, families and society, and has become one of the major public health problems in the world. Therefore, it is of great significance to strengthen the prevention and treatment of COPD. A large number of clinical trials related to COPD have been carried out all over the world, among which statistical analysis methods play a very crucial role in clinical trials. In order to allow clinicians to better interpret the results of clinical trials and standardize clinical trials, so as to provide high-quality research evidence for clinical practice, the commonly used evaluation indicators and statistical analysis methods involved in clinical trials of COPD are introduced below.

The classical theory holds that Type 1 Diabetes (T1D) is a disorder of glucose metabolism caused by massive destruction of pancreatic islet β cells caused by autoimmunity, thus absolutely reducing the amount of insulin secretion. Obvious "three more and one less" symptoms and the onset of diabetic ketosis or ketoacidosis are often regarded as their typical first clinical manifestations. Once T1D patients are diagnosed, except for some patients who experience the "honeymoon period" (referring to some newly diagnosed diabetic patients who have acceptable islet function and can control blood sugar well without insulin within a few months of diabetes diagnosis, this period generally does not exceed half a year), they all need lifelong insulin therapy to maintain their lives, which seriously affects the patient's health and quality of life. Studies have shown that in the past 30 years, the incidence of T1D has increased several times. At present, the incidence of T1D in children in Europe is increasing at a rate of 3% to 5% per year. At the same time, with the in-depth research on the pathogenesis of T1D in recent years, some progress has been made in the prediction and prevention of T1D. In this paper, the latest research on T1D prediction and other aspects will be reviewed in order to provide clues for the development of T1D prediction and prevention research in China.

Bone density is the amount of bone minerals contained in a unit area of bone, which can reflect the metabolism of human bone. Reduced bone mineral density is a common complication in patients with chronic kidney disease (CKD). It is an early stage of osteoporosis and can eventually lead to fracture^[1]。 A large number of studies have proved that fracture can increase the mortality, disability rate and social medical expenses of CKD patients. Therefore, it is very important to evaluate bone quality early to judge the risk of fracture. Bone biopsy is the gold standard for evaluating bone quality, but its application is limited because it is an invasive test and expensive. Therefore, non-invasive bone density detection is more recommended in clinic. Kidney Disease: Improving Global Outcomes (KDIGO) 2017 edition of CKD-mineral and bone Disease (CKD-MBD) guidelines^[2]It is pointed out that bone mineral density detection has predictive value for the risk of fracture in patients with advanced CKD, and it is necessary to pay attention to bone mineral density detection in patients with CKD in all stages. The causes, molecular mechanisms and detection methods of bone mineral density decrease in CKD are reviewed as follows.