2018年 · 第98卷第14期

Kidney disease is a class of common diseases that seriously affect human health. When kidney disease progresses to end-stage kidney disease (ESRD), patients must rely on renal replacement therapy (hemodialysis, kidney transplantation) to survive. The expensive treatment cost brings a huge burden to patients, their families and society, and becomes a heavy topic in China's population health and medical security work. In order to further improve the prevention, diagnosis and treatment of kidney diseases, we need to clarify the current problems, the times and the direction of efforts.

"Precision medicine" is a new concept of disease prevention, diagnosis and treatment. Its core is to take into account the individual differences of each person's genes, environment and lifestyle, and more accurately target specific populations for prevention, diagnosis, targeted therapy and efficacy prediction. In the field of oncology, precision medicine has developed rapidly, gradually realizing the identification and intervention of specific pathways and targets, while chronic diseases such as chronic kidney disease (CKD) are more difficult to achieve precision medicine due to their relatively complex mechanisms. With the continuous deepening of systems biology research, especially genomics research (new generation sequencing technology, genome-wide association analysis, etc.), precision medicine has also achieved certain results in CKD, such as successfully locating new CKD-causing genes (such asINF2, ADCK4and others), discovering new molecular markers and applying them to clinical diagnosis and treatment [such as Gd-IgA1, M-type phospholipase A2 receptor 1 (PLA2R1), etc.]. Focal segmental glomerulosclerosis (FSGS) is one of the common glomerulonephritis, accounting for about 20% of nephrotic syndrome in children, and is one of the common causes of steroid resistant nephrotic syndrome (SRNS) and end-stage renal disease (ESRD) in adults and children^[1]。 Its main pathogenic mechanism is podocyte damage, which in turn leads to impaired glomerular filtration function. FSGS is a kind of disease closely related to genetic factors. With the deepening of genetic research, more than 30 pathogenic genes have been mapped in patients with FSGS, which suggests that the genetic mechanism of this disease is very heterogeneous. Modern clinical medicine is in the transition period from group medicine to individual medicine, and precision medicine will provide new ideas for the diagnosis and treatment of FSGS. The key link of precision medicine is to locate functional molecular mutations related to disease prevention, diagnosis, treatment and prognosis through genetic diagnosis, and formulate personalized medical solutions on this basis. This article will discuss how to carry out the gene diagnosis of FSGS and its significance for clinical diagnosis and treatment.

diabetic nephropathy (DN) is a common microvascular complication of diabetes, and it is also one of the most important causes of end stage of renal disease (ESRD) worldwide, causing a huge social and economic burden. Epidemiological survey data in China show that DN has surpassed glomerulonephritis and become the leading cause of chronic kidney diseases (CKD) in China^[1]。 Unfortunately, at present, the main intervention methods of DN are still mainly symptomatic treatment, including blood pressure control, blood sugar control and improvement of renal hyperperfusion and hyperfiltration, etc. Clinicians still lack appropriate early diagnosis, early intervention and molecular targeting. Sexual drugs delay or terminate the onset and development of DN patients. Therefore, the prevalence of ESRD caused by diabetes has not changed significantly in the past 20 years when other important complications caused by diabetes, such as cardiovascular events and stroke, have been effectively controlled. It can be seen that further interpretation of the novel molecular mechanism of DN, discovery of new molecular diagnostic markers and reveal new molecular intervention targets, so as to build an accurate diagnosis and treatment model of DN, has become the top priority and key to blocking this important chronic disease that affects human health.

At the beginning of the definition of precision medicine, it was determined that it was a new medical concept at the intersection of big data and bioinformatics. Its essence is to use high-throughput output of omics big data and bioinformatics technology to accurately identify molecular markers, and accurately verify and apply them in different diseases or different states of diseases, so as to improve the accurate diagnosis and typing of patients and accurate treatment matching. It can be said that the key technologies of precision medicine research mainly include three levels: first, omics detection technology; Second, bioinformatics analysis technology; The third is to rationally apply big data information to the platform technology of clinical decision-making.

Renal biopsy pathology originally began in the 1920s and was not applied clinically until the 1950s. With the continuous improvement of renal biopsy technology and tissue sample processing, and the progress of immunity, complement and pathogenesis of renal diseases, renal pathology is of great significance to the diagnosis, treatment selection, prognosis and curative effect of renal diseases, and has become an indispensable means for clinical and scientific research of renal diseases. In practice, the same kidney disease sometimes has different pathological phenotypes, and different etiologies can have the same pathological phenotypes. In addition, the diagnosis of some diseases only stays on the kidney pathological phenotype, and lacks pathological diagnosis based on etiology and pathogenesis, while the latter has better guiding significance for clinical treatment.

IgA nephropathy (IgA) is the most common primary glomerulonephritis worldwide. It is characterized by the deposition of IgA-dominated immune complex in the mesangial region of the glomerulus, hence the name. IgA nephropathy is a complex disease, and the pathogenesis of IgA nephropathy has not been fully understood so far. The detection rate of IgA nephropathy varies greatly among various ethnic groups around the world, accounting for 10% to 50% of renal biopsies. A recent survey showed the highest detection rate of IgAN in Asia (39.5%), followed by Europe (22.1%), and the lowest among Latinos (6.1%), suggesting that the disease has a genetic predisposition^[1,2]。 At present, the theory that multiple strikes cause the pathogenesis of IgA nephropathy has been widely recognized by academic circles. This theory holds that patients with IgA nephropathy circulate with IgA1 molecules with abnormal O-glycosylation (one strike) and IgA1 autoantibodies against this abnormal O-sugar chain (two strike). These two proteins combine to form circulating IgA1 complexes (triple strike), and then deposit in the kidney, causing kidney damage (four strike), leading to the occurrence and progression of IgA nephropathy^[3]。

The clinical manifestations of acute PTE lack specificity and are easily missed and misdiagnosed. Suspected patients should be examined based on the clinical likelihood assessment results, and potential other risk factors should be further explored once PTE is diagnosed.

The patient, a 4-year-old and 9-month-old girl, was admitted to the Department of Endocrinology of Peking Union Medical College Hospital in June 2017 mainly because of "clitoral enlargement and accelerated growth for more than 2 years". The patient was the first birth, first birth, normal birth at term cephalic position, with no history of birth injury or asphyxia at birth, with a birth length of 52 cm and a weight of 3.4 kg; Not dark skin tone, female vulva. There was no feeding difficulty since childhood, and the growth and development before the age of 2 were similar to those of the same age. At the age of 2, the height was 90 cm. Thereafter, there began to be accelerated growth, which was 108 cm at 3 years and 2 months, and the height of this visit has reached 126 cm. At the same time, the voice became deeper, the skin tone deepened, and the hair around the body increased and thickened; Pubic hair growth, clitoris enlargement, with white vaginal discharge. In January 2017 (4 years and 4 months), there was no abnormality in blood electrolyte examination in the local hospital (details unknown); Adrenocorticotropic hormone (ACTH) at 8 a.m._8：00) 4.55 pmol/L ( Reference value:<10.12 pmol/L), Blood cortisol_8：00375.36 nmol/L (reference value: 138-690 nmol/L); Follicle-stimulating hormone (FSH) 0.81 U/L, luteinizing hormone (LH)<0.07 U/L, estradiol 145.14 pmol/L, testosterone 11.84 nmol/L, and 17 α hydroxyprogesterone (17 α OHP) 312.76 nmol/L. Pelvic ultrasound showed the development of follicles in the right ovary, the larger one was about 0.5 cm in diameter; Enhanced adrenal CT showed a small nodule with a diameter of 4 mm in the left adrenal region; Bone age was approximately 11 years; The chromosome karyotype is "46, XX". It is considered as "congenital adrenocortical hyperplasia (CAH) is highly likely". Hydrocortisone 10 mg was administered orally twice a day from March 2017, and blood ACTH was re-examined 2 weeks later_8：00<1.10 pmol/L, Blood cortisol_8：00117.30 nmol/L, progesterone 10.52 nmol/L, 17 α OHP 426.41 nmol/L, testosterone 16.40 nmol/L; No mutation was found in CAH-related gene testing, so hydrocortisone was gradually reduced. In June 2017, he visited our department, and the outpatient clinic was admitted to the ward with "the cause of hyperandrogenemia to be investigated". The patient was generally in good condition, his defecation was as usual, and he denied the history of exogenous steroid exposure. The past history and personal history are not special, there is no breast development and menstrual cramps, the parents are not close relatives, and the mother and sister (3 years and 6 months) are hairy since childhood, but their development is roughly normal.

China's aging process is compared with the world average. In 2015, the population over 65 years old reached 9.1%, which has brought greater pressure on limited medical and health service resources. Day surgery usually refers to a mode of surgery in which the patient's admission, surgery and discharge are completed within 1 working day, which in principle does not exceed 48 hours. Common types of day surgery for elderly patients are: cataract removal and lens implantation, hernia repair, anorectal surgery, breast surgery, knee arthroscopy, bladder and prostate surgery, varicose vein surgery, gastrointestinal endoscopy and treatment, etc. Compared to elective surgery, it has some obvious advantages: (1) reduced hospital days and thus hospital-acquired infections; (2) reducing the impact on the patient's life and helping to recover quickly; (3) Reduce the risk of postoperative cognitive dysfunction (POCD); (4) Reduce medical expenses^[1]。 However, day surgery centers in China have started in recent years, and their development models are different. At present, there is no unified standard at the national level. Therefore, this article focuses on the inclusion and exclusion criteria of day surgery for elderly patients, the choice of anesthesia mode, the management of postoperative analgesia and the treatment of complications, etc., hoping to provide help for the standardization of day surgery for elderly patients.

Red blood cells are the most common component of blood transfusion. By increasing circulating red blood cells to increase oxygen carrying capacity and improve tissue oxygen supply, it is one of the common medical interventions. Every year, approximately 85 million international units of red blood cells are transfused worldwide. Typically, a transfusion of 1 international unit of red blood cells (approximately 350 ml) in a normal adult increases the hemoglobin concentration by 10 g/L^[1]。 However, with limited blood resources, increasing the rationality and effectiveness of erythrocyte transfusion can not only reduce the amount of erythrocyte transfusion and the number of transfusions, but also reduce the related risks. This article reviews red blood cell transfusion threshold, recommended guidelines, storage time, blood management plan, etc., hoping to provide reference for clinicians to grasp the indications and related clinical decisions.