Volume 98  ·  Issue 14  ·  2018

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.

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]。

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.

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.

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.

"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.

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.

This study was aimed at investigating the levels and relationships of vascular endothelial growth factor (VEGF) and its receptor(VEGFR) in the bone marrow mononuclear cells (MNC) of chronic mountain sickness (CMS).

A total of 34 patients with CMS and 30 controls residing at altitudes of 3 000-4 500 m were recruited for this study. The levels of VEGF, VEGFR1 and VEGFR2 in bone marrow MNC were detected by flow cytometry technique and RT-qPCR.

The percentage of VEGFR2 positive cells in the bone marrow MNC of CMS were higher than that of the controls[20.7% (8.1%, 67.6%) vs 8.1% (2.2%, 14.9%), P<0.05], but that of VEGFR1-positive and VEGF-positive were similar in CMS and controls. The mRNA levels of VEGFR2 were higher in the bone marrow MNC of CMS than in the controls[1.7(1.0, 5.1) vs 1.0(0.4, 2.7),P<0.05], while VEGF and VEGFR1 mRNA levels were similar between the two groups. The percentage of VEGFR2 positive cells in CMS were significantly correlated with hemoglobin (r=0.453, P=0.007) and the percentage of VEGF-positive cells (r=0.373, P=0.030).

Bone marrow MNC of CMS may show enhanced activity of the VEGF-VEGFR2 pathway, and it appears to be involved in the pathogenesis of CMS.

To prospectively investigate the changes in nutritional status of patients with malignant tumors during hospitalization by using nutritional risk screening (NRS2002), and to analyze the correlation between the nutritional status and clinical outcomes .

This was a prospective and parallel research done by multi-center collaboration from 34 hospitals in China from June to September 2014.Hospitalized patients with malignant tumors inthese departments (Department of Gastroenterology, respiratory medicine, oncology, general surgery, thoracic surgery and geriatrics)were investigated. Only the patients with age≥ 18 years and hospitalization time between 7-30 days were included. During hospitalization, the physical indexes of human bodywere measured, and the NRS 2002 scores, and monitored the nutritional support at the time points of admission and 24 hours before discharge were recorded.And whether there was a nutritional risk in hospitalized patients and its association with clinical outcomes were investigated.

A total of 2 402 patients with malignancies were enrolled in this study. Seventy fourpatients who did not complete NRS2002 were eliminated, and 2 328 patients were included. The number of the main diseases was the top five, including 587 cases of colorectal cancer, 567 cases of lung cancer, 564 cases of gastric cancer, 146 cases of esophageal cancer, and 119 cases of liver tumor. At the time of discharge, compared with admission, the BMI, body weight, grip and calf circumferences of patients with malignant tumor were significantly decreased (P<0.05). The total protein, albumin, prealbumin and hemoglobin were significantly lower than those at admission (P<0.05). In 2 328 patients who were completed nutritional risk screening, the rate of malnutrition at admission was 11.1% (BMI =18.5, 258/2 328) and the rate of malnutrition at discharge was 10.9% (BMI =18.5, 254/2 328), there were no significant differences (χ²=0.019 7, P=0.888). There were 1 204 patients with nutritional risk at admission (51.7%, NRS2002 score≥3)and 1 352 patients with nutritional risk at discharge (58.1%, NRS2002 score≥3), with significant differences (χ²=49.9, P<0.001). The incidence of nutritional risk in patients with colorectal, stomach, and lung tumors at discharge was significantly higher than that at admission (P<0.05). The infective complications and other complications of patients with nutritional risk were significantly greater than those without nutritional risk at admission and at discharge.ICU hospitalization stay of patients with nutritional risk was increased significantly than those without nutritional risk at admission(P=0.042). Hospitalization expenses of patients with nutritional risk was increased significantly than those of patients without nutritional risk at discharge(P<0.01).

The patients with malignant tumor have a higher incidence rate of malnutrition at both admission and discharge and malnutritionhas correlation with adverse clinical outcomes.The aboveindicators did not improve significantly at discharge.Doctors should pay more attention to the nutritional status (screening and evaluation)of patients before discharge and use appropriate and adequate nutrition support in order to prevent the weight loss and improve the life quality of patients.

To determine the influence of urethral fibrosis on the recovery of urinary continence after laparoscopic radical prostatectomy.

A retrospective study of 203 patients from January 2010 to January 2014 who were underwent laparoscopic radical prostatectomy for prostate cancer in the First Affiliated Hospital of Fujian Medical University. The patients were divided into 2 groups according to preoperative T2-weighted magnetic resonance imaging of fibrosis status of the urethral wall and periurethral tissue. One hundred and forty-four(≤2 grade) and 59 (≥3 grade) were classified into the no/mild and severe urethral fibrosis groups respectively. Urinary continence at 1, 3, 6, 12 months after operation were compared between this two groups respectively.

There was no significant difference in the two groups with respect to age, body mass index (BMI), Charlson comorbidity index (CCI), international prostate symptom score (IPSS), prostate volume, preoperative prostate-specific antigen value, nerve-sparing procedure, postoperative Gleason score and pathological stage. The operation was completed successfully in all cases. With a median follow-up time of 15 months (ranged from 12 to 24 months), there was no statistical difference between the two groups in urinary continence at 1 month after operation (P>0.05). The incidences of continence in patients with no/mild fibrosis were significantly higher at 3, 6, 12 months after operation than those with severe fibrosis. (In the no/mild fibrosis group and severe fibrosis group, the continue rate at 3 mouths was 50.0% vs 28.8%P=0.005; at 6 mouths was 91.0% vs 59.3% P<0.001; at 12 mouths was 98.6% vs 88.1%P=0.003).

Preoperative urethral fibrosis could be a significant predictor of recovery of the long-term urinary continence status after laparoscopic radical prostatectomy. Compared with no/mild fibrosis, severe fibrosis had worse long-term continence status.

To explore the effect of berberine on chronic inflammatory pain and the comorbid depression and the associated mechanisms.

Forty healthy male ICR mice (2 months, 25-30 g) were used in the present study. The chronic inflammatory pain was induced by intraplantar injection of complete freund′s adjuvant (CFA) to the hind paws. All animals were divided into 4 groups (n=10 for each group) according to random number table: the saline group (group A), the chronic pain group (group B), the saline+ berberine group (group C) and the chronic pain+ berberine group (group D). The baseline data of pain and depressive performance were measured on the day before any drug treatment.On d1, mice of B and D groups received intraplantar injections of 50 μl CFA emulsion (1∶1 diluted with saline); mice of A and C groups received intraplantar injections of the same volume of saline. During d15-d21, mice of C and D groups received intraperitoneal injections of berberine (50 mg/kg, daily for 7 days); mice of A and B groups received the equal volume of saline. The Hargreaves tests and the Von Frey tests were conducted before the injection of CFA and on d7, d14, d17 and d21 to measure the thermal and mechanical pain thresholds. The forced swimming tests and novelty-suppressed feeding tests were performed before the injection of CFA and on d21 to measure the depressive performance. After the behavioral tests, the levels of inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) at the lumbar (L4-L5) spinal cord were examined by enzyme-linked immunosorbent assay(ELISA). The mRNA level of chemokine C-C motif ligand 2 (CCL2) in the lumbar spinal cord was examined by quantitative real-time polymerase chain reaction(qRT-PCR).

Compared with group A, the thermal withdrawal latency of group B mice on d7, d14, d17, d21 was declined[(3.40±0.67)s vs (10.55±1.58)s, (7.49±1.04)s vs (11.47±1.92)s, (6.46±0.56)s vs (11.60±1.86)s, (6.04±0.54)s vs (10.33±1.59)s, all P<0.01], and the mechanical threshold was also decreased[(0.15±0.03)g vs (0.78±0.24)g, (0.23±0.12)g vs (0.60±0.16)g, (0.30±0.12)g vs (0.72±0.25)g, (0.40±0.00)g vs (0.72±0.19)g, allP<0.01], on d21 the immobility time was increased[(161.60±35.79)s vs (88.92±53.24)s ,P<0.05]and the time of feeding latency was decreased[(227.40±57.5)s vs (77.25±26.45)s,P<0.01], suggesting that CFA could induce hyperalgesia and depression. After berberine treatment (daily for 7 days), compared with group B, the thermal withdrawal latency of group D mice was increased[(9.99±2.68)s vs (6.04±0.54)s,P<0.01], the mechanical threshold was elevated[(0.80±0.21)g vs (0.40±0.00)g,P<0.01], the immobility time was decreased[(92.97±44.31)s vs (161.60±35.79)s,P<0.05], and the feeding latency was declined[(105.00±50.00)s vs (227.40±57.5)s,P<0.01]. Compared with group A, the concentrations of spinal IL-1β, IL-6 and TNF-α in group B were increased[(29.90±4.87)pg/ml vs (21.00±5.46)pg/ml, (131.10±26.12)pg/ml vs (60.68±23.47)pg/ml, (21.54±4.93)pg/ml vs (11.39±3.66) pg/ml , allP<0.01], the mRNA level of CCL2 was upregulated[(2.21±0.60) vs (1.00±0.37),P<0.01]. After berberine treatment (daily for 7 days), compared with group B, the concentrations of IL-1β, IL-6 and TNF-α in group D were decreased[(19.44±4.83)pg/ml vs (29.90±4.87) pg/ml , (57.82±32.28)pg/ml vs (131.10±26.12)pg/ml , (9.29±2.46)pg/ml vs (21.54±4.93) pg/ml, allP<0.01], the mRNA level of CCL2 was downregulated[(1.33±0.40)vs (2.21±0.60),P<0.05].

Berberine can reverse chronic inflammatory pain induced by CFA and alleviated the comorbid depression. Its anti-nociceptive and anti-depressive effects may associate with downregulation of the spinal levels of the inflammatory cytokines and mRNA transcription of CCL2.

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.

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.

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.