2018年 · 第98卷第32期

Prostate cancer (PCa) is one of the most common malignant tumors in men and one of the leading causes of cancer-related death in men worldwide, ranking second in cancer mortality among men^[1]。 Although the understanding and treatment of PCa has improved greatly over the past few years, the molecular regulation and pathogenesis of PCa cell growth have not been fully elucidated. Patients with early PCa are usually treated with surgery and radiation therapy^[2]For advanced PCa, the treatment strategy based on endocrine therapy is often used clinically, that is, androgen removal therapy^[3]。 However, continuous deandrogenation still inevitably leads to the development of androgen-dependent PCa to androgen-independent PCa, i.e. castration-resistant PCa (CRPC), which causes great obstacles to the clinical treatment of PCa^[4]。 Studies have found that autophagy plays a key role in the process of castration resistance produced by deandrogenation treatment. Autophagy is the process of degrading abnormal cellular components into nutrients such as amino acids, lipids, nucleotides, and carbohydrates and redistributing them to cells for recycling. The degraded cellular components are first surrounded by a double membrane structure to form phagocytic vesicles, which gradually fuse and mature into autophagosomes, and then autophagosomes combine with lysosomes to form autophagic lysosomes, thus realizing the recycling and reuse of degradation products^[5]。 It has long been widely believed that autophagy plays diametrically opposite roles at different disease stages. For example, in the early stages of tumorigenesis, autophagy can reduce the accumulation of abnormal genes and proteins to inhibit tumorigenesis. However, increasing evidence suggests that autophagy plays a protective role against advanced PCa, especially under conditions such as hypoxia, nutrient supply deficiency, chemotherapy, etc., and can promote tumor cell survival and adaptation by eliminating the accumulation of toxic proteins and providing nutrient sources^[6]。 Moreover, the self-recycling supply of nutrients and energy by autophagy may even further promote the anabolic process of the tumor, thereby accelerating the development of prostate cancer^[7]。 Therefore, autophagy is a "double-edged sword" for the occurrence and development of PCa. It is particularly important to understand the important role of autophagy in the development mechanism of PCa and explore the potential of autophagy for the treatment of PCa. The role of autophagy in the development of prostate cancer and its molecular mechanism are described below.

Benign prostatic hyperplasia (BPH) is the most common benign disease with urinary disorders in middle-aged and elderly men. About 30% of patients with BPH will progress to advanced stage, and about 40% of patients with advanced BPH need surgical treatment. Prostatectomy is an effective means to treat advanced BPH. Most resections of the prostate require removal of the urothelium of the urethra in the prostate region.

Epidermal growth factor receptor (EGFR) gene mutation is the most common driver gene mutation in non-small cell lung cancer (NSCLC) in East Asian population, with an incidence of 30% ~40%^[1,2]。 Several previous studies have supported that EGFR-tyrosine kinase inhibitor (TKI) monotherapy is the standard treatment regimen for patients with locally advanced or metastatic NSCLC with EGFR gene mutations, but most patients will develop drug resistance 9 to 14 months after administration^[3,4,5,6]Among them, missense mutation in exon 20 of EGFR gene (i.e. T790M mutation) is the most dominant type of drug resistance mutation. At present, the positive rate of T790M mutation in EGFR-TKI resistant tissue samples is about 60%^[7,8]However, the positive rate of T790M mutation in plasma samples varies greatly based on different methods, ranging from 23% to 63%^[9,10,11]。

A 35-year-old female was seen in the outpatient department of Peking Union Medical College Hospital on October 25, 2017 due to "polydipsia, polydipsia, polyuria, amenorrhea for 1 and a half years and galactorrhea for 6 months". In April 2016, the patient developed polydipsia, polydipsia (5 L/d), polyuria (4~5 L/d), nocturia 5~6 times/night, self-complaining of dry skin, no menstrual cramps in that month, and no other accompanying symptoms. In September 2016, I went to a local hospital and found that my visual acuity in both eyes decreased slightly, without strabismus, diplopia, visual field defect, and eyelid ptosis. B-ultrasound of uterus showed thinning of the endometrium (0.2 cm), smaller uterine body (3.8 cm ×2.6 cm ×2.6 cm), and smaller bilateral ovaries (2.4 cm ×1.2 cm); Prolactin (PRL) 2.90 nmol/L (reference value:<1.37 nmol/L), estradiol 32.94 pmol/L (reference: 73.2-322.1 pmol/L), follicle stimulating hormone (FSH) 3.09 U/L and luteinizing hormone (LH) 0.85 U/L. Enhanced magnetic resonance imaging (MRI) of the pituitary gland: the suprasellar region occupies a mass, with a size of 0.6 cm ×0.6 cm ×0.8 cm, which is closely related to the pituitary stem, and no significant enhancement is observed. After treatment with progesterone and traditional Chinese medicine (specific unknown), menstruation still did not resume. In April 2017, the patient found that after squeezing the breast, milky discharge was visible, milky white, without bloodstreaks, so he went to the neurosurgery department of another hospital for examination: urine specific gravity: 1.005; There were no obvious abnormalities in blood routine and blood biochemistry; Antinuclear antibody (ANA) (+) 1:320 (homogeneous spot type), anti-ribonucleoprotein (RNP) antibody (+), anti-SSA antibody (+), proliferative nuclear antigen antibody (PCNA) (+); anti-neutrophil cytoplasmic antibody (ANCA) (−); a tumor marker (-); blood alpha-fetoprotein (AFP), human chorionic gonadotropin (β-HCG) (−); Cerebrospinal fluid: conventional, biochemical (-), looking for tumor cells (-). The other hospital considered "suprasellar area occupation, central diabetes insipidus", and gave desmopressin acetate tablets (micing) (oral, 25 μ g/time, twice/d) and bromocriptine (oral, 1.25 mg/time, once/d). The patient's symptoms of polydipsia, polydipsia and polyuria were significantly relieved, drinking water 2 L/d, urine volume 1.5 L/d, nocturia 1~2 times/night, but there was still no menstrual cramps, and milky white liquid still spilled out after squeezing the breast, so bromocriptine was stopped in September 2017. During the course of the disease, there was no fever, oral ulcer, joint pain, bone pain and other symptoms, and he was admitted to our hospital for further diagnosis and treatment. Since the onset of the disease, the patient's spirit, sleep and appetite are good, his stool is normal, his urine is as mentioned above, and his weight has not changed significantly. Past history: Cesarean section at 42 weeks of gestation in 2011 gave birth to a 3 kg male baby. History of marriage and childbirth: age-appropriate marriage and childbirth, spouse physical health. Menstrual history: Menarche 14 years old, menstrual days 4 days, menstrual cycle 25~28 days, last menstrual on May 10, 2016. Personal history and family history are no different.

A 76-year-old female was admitted to the First Affiliated Hospital of Zhejiang University School of Medicine on October 11, 2017 due to chest tightness, dizziness for 1 year and syncope twice 12 years after coronary stent implantation. The patient underwent coronary stenting 12 years ago due to coronary atherosclerotic heart disease (specifics unknown) and regularly took isosorbide mononitrate and aspirin. One year ago, chest tightness, accompanied by dizziness, and a squeezing sensation occurred during the attack. It occurred once a few days and lasted for several minutes. It was induced when tired or mood fluctuated and could be relieved by itself. Half a month ago, syncope occurred after standing for a long time (about 20 min), and automatically regained consciousness after 1~2 min. Before syncope, there were symptoms of chest tightness and dizziness. Tracing back to the medical history, there was a similar attack 1 year ago. At present, the patient still has chest tightness and dizziness, which is aggravated after activity, mildly limited activity, and it is difficult to go up the stairs. For further diagnosis and treatment, the outpatient clinic was admitted to the hospital with "hypertension, coronary atherosclerotic heart disease".

A 60-year-old male was admitted to the gastroenterology ward of Peking Union Medical College Hospital on September 12, 2017 for diagnosis and treatment due to "chronic diarrhea for 3 months, abdominal pain with bloody stool for more than 1 month". Three months before admission, the patient developed diarrhea, loose stools 3 to 4 times a day, without pus and blood, and colonoscopy in an external hospital showed mild mucosal edema of ascending colon to sigmoid colon, without erosion or ulcer. Self-administered antidiarrheal drugs are ineffective. One month ago, the patient had sudden periumbilical colic without obvious trigger, and the pain score was 5 points, accompanied by brown bloody stool defecation of about 500 ml, tenesmus and then severe, no fever, vomiting, amaurosis, etc., and abdominal pain improved after defecation. The next day, blood and watery stool were discharged 20 to 30 times, 20 to 50 ml each time. A large number of red and white blood cells were found in routine fecal examination in other hospitals, and occult blood was positive; Erythrocyte sedimentation rate was 18 mm/h, hypersensitive C-reactive protein 77 mg/L, and anti-neutrophil cytoplasmic antibody was negative. Colonoscopy showed congestion, edema, roughness, erosion, bleeding and ulcer formation in the mucosa of ascending, transverse, descending and sigmoid colon, but no abnormalities in the rectum were found. Pathological report: Chronic inflammation of mucosal tissue with formation of small focal crypt abscess. Abdominopelvic enhanced CT: Irregular thickening and visible enhancement of the local intestinal wall of the transverse colon. Considering not excluding inflammatory bowel disease, prednisone 40 mg/d (equivalent to 1 mg/kg per day), mesalazine 4 g/d, intestinal probiotics and enteral nutrition were given. Abdominal pain was relieved compared with before, but blood and watery stool were still discharged 10 to 12 times a day, 20 to 50 ml each time. After 2 weeks of adequate hormone therapy, he turned to watery stools more than 10 times a day. Weight loss of 14 kg after onset. Deny repeated oral ulcers, vulvar ulcers, joint swelling and pain, etc. Past history: In 2016, I underwent thoracoscopic enlarged thymectomy due to "thymoma and myasthenia gravis", and regularly took bromophenostigmine after the operation. Hyperlipidemia, denied history of coronary heart disease without taking lipid-lowering drugs. Personal History: Has a long history of smoking and denies alcoholism. Admission physical examination: vital signs were stable, the superficial lymph nodes of the whole body were not swollen, surgical scars were visible on the chest, the heart and lungs were not different, the abdomen was soft, the middle and upper abdomen were mild tender, no rebound pain, the liver and spleen were not reached under the costs, and the abdominal mass was not reached, intestinal sounds were 3~4 times/min, and there was no edema in the lower limbs.

The patient, a 52-year-old male, was admitted to the Department of Metabolic Endocrinology, Xiangya Second Hospital, Central South University on July 14, 2017, mainly due to "fever for 3 months, polyuria and polydipsia for 2 months". The patient went to the local hospital on April 27, 2017 due to fever and oliguria. The blood creatinine was measured at 799.6 μ mol/L, and the epidemic hemorrhagic fever antibody was positive. He was diagnosed with hemorrhagic fever with renal syndrome and acute renal failure. After symptomatic treatment such as anti-infection and hemodialysis, the symptoms of fever and oliguria were relieved, and the blood creatinine was re-measured at 253.3 μ mol/L. On May 21st, he developed symptoms of polyuria and polydipsia, drinking 4,000~5,000 ml of water and 4,000~6,000 ml of urine daily. The local hospital considered the polyuria stage of renal failure and gave symptomatic treatment, but the effect was not good. Symptoms of anorexia, nausea, fatigue, fear of cold and loss of libido gradually appear. Thyroid function checked locally on June 15: free triiodothyronine (FT₃) 3.23 pmol/L (reference value: 3.54-6.57 pmol/L), free thyroxine (FT₄) 5.43 pmol/L (reference value: 11.40-23.20 pmol/L), thyroid stimulating hormone (TSH) 0.156 mU/L (reference value: 0.510-4.940 mU/L); Sex hormone test: testosterone 1.06 nmol/L (reference value: 8.20~27.0 nmol/L), luteinizing hormone (LH)<0.07 U/L (reference value: 1.48-9.40 U/L), follicle stimulating hormone (FSH) 0.45 U/L (reference value: 1.40-17.80 U/L); Magnetic resonance imaging (MRI) of the pituitary gland: thinning of the pituitary gland with mild enhancement, considering adenohypopituitarism. Prednisone was given 5 mg/time, 2 times/d orally, and levothyroxine sodium tablets 50 μ g/time, 1 time/d orally after 1 week. The symptoms of nausea, fatigue and cold sensitivity were alleviated, and the symptoms of polyuria and polydipsia were still present. The daily urine volume was 4,000~5,000 ml, and the water consumption was 3,000~4,000 ml. In order to clarify the cause of polyuria, we were admitted to our department. Past history: I was diagnosed with type 2 diabetes 1 year ago without treatment. On April 21st, I went to a local hospital due to dry mouth and dizziness. My fasting blood glucose was checked at 22.3 mmol/L, and I was given "recombinant human insulin combined with insulin glargine" treatment. After the blood glucose improved, the dose was gradually reduced to discontinuation. The insulin was used for half a month. After discontinuation, the fasting blood glucose was monitored at 4~5 mmol/L, and the blood glucose was 5~7 mmol/L 2 hours after meals. Personal history: Born in Xiangyin County, Hunan Province, living alternately in Xiangyin County and the suburbs of Guangzhou. All house mice live in Guangzhou, but there is no direct contact, and there is no similar disease in his family.

Asthma is a chronic airway disease characterized by reversible airflow obstruction, airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling. Obesity is considered one of the most important public health problems of the 21st century. Many studies have shown that^[1]There is a significant correlation between obesity and the onset of asthma. The relationship between the two is increasingly valued, and the 2012 edition of the International Consensus on Childhood Asthma lists obesity asthma as a special phenotype of asthma^[2]。 Obesity asthma is characterized by more severe symptoms, unstable or lack of asthma control, predominantly non-eosinophilic airway inflammation and steroid resistance, and therefore its clinical treatment faces greater challenges^[3]。 It is currently believed that there are at least two distinct major phenotypes of obesity asthma: an early-onset allergic type that is complicated with obesity and a late-onset non-allergic type that occurs only in the context of obesity. Both phenotypes have asthmatic manifestations, but they respond differently to weight-loss treatments. Significant improvement in symptoms and AHR after weight loss in patients with delayed onset non-allergic obese asthma, whereas only symptoms and no improvement in AHR in patients with early onset allergic obese asthma^[4]。 AHR, as an essential feature of asthma, can be produced in simply obese individuals^[5]The above differences also exist in different phenotypes of obese asthma. Therefore, the study of the mechanism of AHR in obesity and asthma is an important entry point for the study of the potential association mechanism between obesity and asthma.

Induced sputum technique is a non-invasive diagnostic and detection method that promotes the production and discharge of sufficient sputum by inhalation of hypertonic saline. The induced sputum comes from the lower respiratory tract, is not easily affected by squamous epithelial cells, and can better represent the pathophysiological characteristics of the lung^[1]。 At the beginning of the 21st century, the application of sputum induction technique in respiratory diseases is still relatively simple. It is mainly applied to bronchial asthma (asthma) and chronic obstructive pulmonary disease (COPD), which are two chronic airway inflammatory diseases, with good safety and repeatability^[2,3]。 A large number of previous studies have evaluated the type and level of airway inflammation mainly by detecting the inflammatory cell count and inflammatory factor level in induced sputum. However, with the updating of technology and knowledge in the field of respiratory diseases and the rapid progress of molecular biology and immunology, sputum induction technology has been widely used in respiratory diseases in recent years. The research findings, new technologies and extended applications of sputum induction technique in respiratory diseases in the past 10 years are summarized as follows.

Intravitreal injection of drugs is a common treatment in ophthalmology. In recent years, the surgical volume of intravitreal injection of drugs has increased exponentially. According to Medicare data, the proportion of intravitreal drug injections in ophthalmic surgery increased from 0.55% (2 922/527 050) in 2000 to 86.91% (2 619 950/3 014 629) in 2014^[1]。 For blinding eye diseases such as wet age-related macular degeneration and diabetic macular edema, intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs has become the first treatment option. Due to the increasing number of patients undergoing cataract surgery after intravitreal injection of anti-VEGF drugs in the past, in recent years, researchers have begun to pay attention to the correlation between the history of intravitreal injection of anti-VEGF drugs and cataract surgery complications. This article mainly discusses the research progress on the correlation between intravitreal injection of anti-VEGF drugs and posterior capsule rupture, postoperative endophthalmitis and intraocular hypertension in cataract surgery.