Volume 99 ·  Issue 43 ·  2019

In order to promote the standardized detection of clinical high-throughput sequencing technology, the Beijing Expert Consensus on Standardized Application of Clinical Testing of High-throughput Sequencing Technology (General Part of the First Edition) is released. For the clinical application of high-throughput sequencing technology, it is essential to set clear clinical intended use, establish methods to meet clinical intended use, report and interpretation of results. Clinical laboratories should pay attention to the standardization of clinical application of high-throughput sequencing technology to avoid clinical abuse and misuse.

epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) with EGFR-sensitive mutations. Tissue is the first choice for EGFR gene mutation detection. Plasma EGFR gene mutation in advanced NSCLC patients is in good agreement with tissue, which is a supplement to tissue detection. circulating tumor DNA (ctDNA) in plasma is low in content and short in fragments, which is easily contaminated by wild-type DNA in blood. Blood sample collection, ctDNA extraction, quality control of each detection link and standardized training of detection technicians all affect the accuracy of plasma EGFR gene mutation test results. This paper summarizes the problems that should be paid attention to in the detection of plasma EGFR gene mutation in patients with advanced NSCLC.

The incidence of genetic diseases is low, there are many kinds of diseases, and the diagnosis is difficult. Accurate genetic diagnosis of genetic diseases is the basis of disease management and treatment for patients and families. The development of high-throughput sequencing technology has greatly improved the expectation of genetic diagnosis for patients with genetic diseases. However, how to establish a reliable next-generation sequencing technology (NGS) detection method and how to analyze and interpret the sequencing data is one of the key problems to be solved in genetic detection of genetic diseases in China. This paper analyzes and expounds the possible problems and challenges in clinical data analysis and interpretation of laboratories engaged in NGS detection of genetic diseases in China from three aspects: establishment and confirmation of data analysis process of genetic diseases, clinical validity of detected genes and classification and interpretation of sequence variation.

Joint surgery in China has experienced decades of development, especially in the past 20 years, it has made great progress in all aspects. These achievements are inseparable from the strong support and guidance of various professional academic organizations at all levels. We still need to see the gap with the world's advanced level. At the same time, it is more necessary to face the problems and shortcomings existing in the development of artificial joint surgery in China, and strive for the future development goal of minimally invasive, accurate and personalized artificial joint surgery.

The treatment of severe trauma needs not only scientific and efficient treatment standards, but also the establishment of corresponding treatment system. This paper summarizes the progress and current situation of regional trauma treatment system construction in China and looks forward to the next main work.

Many progress has been made in the field of trauma and orthopedics at home and abroad in recent years. This paper analyzes and forecasts the development status of some key development fields of trauma and orthopedics. It mainly includes the development of minimally invasive surgery technology, the application of precision surgery technology, the research of multidisciplinary management mode of elderly hip fracture, the application of accelerated rehabilitation surgery in trauma and orthopedics, and postoperative rehabilitation of fracture.

With the continuous development of science and technology, new technologies and ideas in the field of spinal cord emerge one after another. In recent years, the basic research of spine has made great progress; 3D printing technology plays an increasingly important role in optimizing surgical plans and realizing personalized customization of prostheses; The concept of spinal non-fusion and minimally invasive technology have also occupied a place in clinical practice. This article summarizes and summarizes the above-mentioned developments, in order to make readers more comprehensively understand the new ideas and new developments in the field of spinal cord.

high-throughput sequencing (HTS) is next generation sequencing (NGS), also known as massively parallel sequencing (MPS). Compared with traditional sequencing technology, high-throughput sequencing single-base detection has lower cost, faster speed, and can detect a large number of target genes at a time. Therefore, it is widely used in non-invasive prenatal screening of chromosome aneuploidy, tumor targeted therapy gene mutation detection, hereditary tumor detection, genetic disease and rare disease detection, pathogenic microorganism and metagenome detection, preimplantation genetic screening and preimplantation genetic diagnosis^[1]。

Although China's health undertakings are developing rapidly, the situation of insufficient per capita medical resources and unbalanced resource allocation has not fundamentally changed, and there is still a gap between the development of medical and health undertakings and people's requirements for a better life. Medical equipment, especially medical talents, are scarce in grass-roots rural areas and central and western regions. Even in first-tier cities such as Shanghai, there is an obvious unbalanced distribution of medical resources between regions, and the problem of difficulty in seeing a doctor has not been completely solved^[1]。 In accordance with the "Healthy China 2030" planning outline and the "Guiding Opinions on Promoting the Construction of Hierarchical Diagnosis and Treatment System"^[2]Requirements, establish a complete medical system with the first diagnosis at the grass-roots level and referral from the top to the bottom, realize the complementarity of medical advantages and resources between regions, and promote the process of homogenization of urban and rural medical and health services. In response to the requirements of national strategy and the rapid development of interconnected technology, medical services can break through the limitations of time and space, among which the characteristics of medical imaging make it naturally play a vanguard position in "Internet plus" medical care^[3]。

To assess the technical success rate, stent patency, clinical efficacy and complications of stent placement for filter-related chronic occlusion of the inferior vena cava.

A retrospective analysis was carried out for 12 patients with filter-related chronic occlusion of the inferior vena cava associated with severe post-thrombotic syndrome, who underwent stent placement after ineffective conservative therapy at Nanjing First Hospital from March 2016 to December 2018,9 males and 3 females, aged from 48 to 77 years, mean age 60 years, six had bilateral lower extremity symptoms and six had unilateral lower extremity symptoms.Technical success rate, stent patency, clinical efficacy and complications of stent placement were recorded. Clinical success was defined as relief of symptoms and a decrease in clinical, etiology, anatomy, and pathophysiology (CEAP) score for at least grade 1.

Stent placement in the unilateral or bilateral iliocaval occlusion was successful in 11 patients. The cause of technical failure in the single patient with failed stent placement was an inability to cross the occluded left iliacvein and the patient was treated with stent placement in the right iliocaval vein.There were 7 patients with inferior vena cava and unilateral iliocaval stent placement; 5 patients with inferior vena cava and bilateral iliocaval stent placement. Acute stent thrombosis occlusion occurred in 1 case after the operation, the blood flow recanalized after catheter-directed thrombolysis and re-stenting. All patients were followed up for 6 to 24 months, with an average of (13±6) months. During the follow-up period, CTV or venography of lower limbs showed that the blood flow in the stent was unobstructed. At the last follow-up, 12 patients were evaluated as clinically effective. Three patients had transient treatment of lateral lumbar pain during operation, which alleviated by themselves.No significant abdominal pain, severe hemorrhage, symptomatic pulmonary embolism and other complications related to treatment occurred in all patients during perioperative period and follow-up.

Stent placement is safe and feasible in the treatment of filter-related chronic occlusion of the inferior vena cava, which can alleviate the clinical symptoms of severe post-thrombotic syndrome.

To investigate the incidence and related risk factors of ulnar nerve dysfunction after open reduction and internal fixation of humeral intercondylar fractures.

A total of 168 patients who underwent open reduction and plate and screw fixation of a humeral intercondylar fracture between January 2013 and May 2017 were retrospectively analyzed. There were 85 males and 83 females, aged from 14 to 77 years with a mean age of (43±17) years. Diagnosis of ulnar neuropathy was defined as documentation of sensory and motor dysfunction of the ulnar nerve in the medical record. The explanatory (independent) variables included age, gender, injury type, AO typing, time from injury to surgery, surgery approach, plates fixation methods and whether the nerve was transposed. Univariate and multivariate analyses were performed to determine risk factors associated with postoperative ulnar nerve dysfunction.

Acute injury-related ulnar nerve neuropathy was diagnosed in 12(7.1%) of 168 patients. Among the other 156 patients without preoperative ulnar nerve neuropathy,the total postoperative ulnar neuropathy was found in 52 patients (33.3%), and in 26(16.7%) at the final follow-up, according to the McGowan grades system; 23(88.5%) of 26 patients were clinically graded as grade 1, and 3(11.5%) were graded as grade 2. Multivariate logistic analysis showed that triceps sparing approach (OR=2.639, P=0.039) and parallel double plate fixation (OR=3.089, P=0.046) were associated with a risk of postoperative ulnar nerve dysfunction.

There is a substantial incidence of postoperative ulnar nerve dysfunction after open reduction and plate and screw fixation of humeral intercondylar fracture, postoperative ulnar neuropathy may occur from the time of injury through the long-term follow-up period, triceps sparing approach and parallel double plate fixation are the risk factors for ulnar neuropathy.

To investigate the application value of motor unit number index (MUNIX) for diagnosis and assessment progress in patients with amyotrophic lateral sclerosis (ALS).

Sixty healthy controls and 60 ALS patients in the clinic were enrolled from May 2017 to December 2018. The bilateral deltoid, abductor digiti minimi, quadriceps femoris and tibialis anterior muscles of the subjects were detected by MUNIX method, and the negative peak amplitude of compound muscle action potential (CMAP) of ulnar nerve, femoral nerve, peroneal nerve, axillary nerve in bilateral was collected. MUNIX and motor unit size index (MUSIX) of muscles were compared between ALS group and control group. The difference between the MUNIX abnormal rate of muscles and abnormal rate of the corresponding CMAP negative peak amplitude in ALS patients was further compared. Meanwhile, the correlation between the disease course of ALS patients and MUNIX and MUSIX was analyzed.

Compared with the control group, the MUNIX values of the deltoid, abductor digiti minimi, quadriceps femoris and tibialis anterior decreased significantly (97±24 vs 183±38, 48±17 vs 191±39, 54±15 vs 159±22, 49±16 vs 147±25, all P<0.05). MUSIX values increased ((175±32) μV vs (47±15) μV, (189±34) μV vs (54±16) μV, (170±30) μV vs (49±13) μV, (190± 36) μV vs (48± 14) μV, allP<0.05)). In ALS patients, the abnormal rate of MUNIX was respectively 81%, 87%, 75% and 89%. The negative peak amplitude abnormal rate of corresponding neuralCMAP was 35%, 40%, 31% and 36%, respectively, with a significant difference (P<0.05). There was a negative correlation between MUNIX value and the course of disease in ALS patients (P<0.05), and a positive correlation between MUSIX value and the course of disease (P<0.05).

The MUNIX technique exhibits the features of quantifying the proximal upper and lower limb muscles and assessing the loss of motor units in motor neuron degeneration.

To evaluate the value of CT in the differential diagnosis of Pseudomonas aeruginosa sinusitis and fungal ball in paranasal sinus caused by Aspergilus flavus.

In this retrospective study, CT results of 74 cases of Pseudomonas aeruginosa sinusitis including 31 male cases and 43 female cases with age onset from 15 to 74 years old (mean±SD was 50±13) and 72 cases of fungal ball in paranasal sinus caused by Aspergilus flavus including 28 male cases and 44 female cases with age onset from 25 to 78 years old (mean±SD was 53±15) at Beijing Tongren Hospital confirmed by histopathology were enrolled from January 2013 to May 2017. The CT characteristics of the two groups of cases were compared using χ ² test, and P<0.05 was considered statistically significant.

Soft tissue opacification of the involved paranasal sinus was found on CT in each case of the two groups. There were significant differences in the rate of single sinus involvement (44.6% and 90.3% respectively), the incidence of lesion associated with maxillary sinus (91.9% and 70.8% respectively), ethmoid sinus (41.9% and 2.8% respectively), frontal sinus (29.7% and 0 respectively), calcification (50.0% and 72.2% respectively), and the enlargement of maxillary sinus opening (13.2% and 35.3% respectively), in addition to the central calcification (83.8% and 59.6% respectively) between the two groups (all P<0.05). However, the incidence of sphenoid sinus involvement (32.4% and 34.7% respectively), bone sclerosis (56.8% and 62.5% respectively) or destruction(18.9% and 16.7% respectively) were not found different between the two groups (P>0.05).

Though the CT findings are similar between the two diseases such as soft tissue opacification of the involved paranasal sinus with calcification and bone sclerosis or destruction, there are still a few characteristics on CT in differentiating the one from the other. The involvement of multi-sinuses, maxillary sinus, ethmoid sinus and frontal sinus, the central calcification are more common in the Pseudomonas aeruginosa sinusitis. However, the CT features including single sinus involvement, calcification and enlargement of maxillary sinus opening, can be seen more often in the fungal ball in paranasal sinus caused by Aspergilus flavus.

To explore related factors affecting evolution of recent small subcortical infarct (RSSI) with small-artery occlusion.

A total of 96 RSSI patients with RSSI were admitted from Shanghai Tongji Hospital between January 2015 and December 2018. The age of patients containing 60 men was 64.5 (58-73) years, and MRI follow-up time was 11.6 (6.3-11.8) months. Clinical information of patients, images data at baseline head MRI and evolution outcomes at follow-up MRI were collected. All patients were divided into cavitation group (lacunes) and no cavitation group (white matter hyperintensities (WMH) and disappearance) to analyze related factors.

Fifty-nine cases (61.5%) developed to cavities, 32 cases (33.3%) were focal WMH, and 5 cases (5.2%) disappeared.In the univariate analysis, RSSI maximum diameter on the DWI or T₂WI sequence of cavitation group was significantly higher than non-cavitation group, but male proportion was lower (11.6 (9.9-16.6) vs 8.6 (6.9-13.0) mm, 11.8 (9.7-16.2) vs 8.8 (6.7-13.1) mm, 54.2% vs 75.7%, all P<0.05). In Logistic regression analysis,the maximum diameter on DWI sequence was an independent predictor of cavity formation (P=0.022,OR=1.138).When conducting quantitative analysis of infarct diameter and taking infarct maximum diameter ≤10 mm group as reference, the cavitation risk of maximum diameter>15 mm group was about 7.5 times higher (P=0.010, OR=7.464). The maximum diameter of 10-15 mm lost predictive value for cavity formation (P=0.129, OR=2.444).

About 61.5% of RSSI develop to cavitation and 38.5% to WMH or disappear. The RSSI showing larger diameter on DWI has a greater possibility of cavitation.

To investigate the detection rate of pulmonary nodules and the accuracy of automated measurement in chest simulation phantom by artificial intelligent computer-aided detection of pulmonary nodules with different pre-adaptive iterative techniques (ASIR-V) in wide-spectrum CT scanning.

Sixteen pulmonary nodules with different diameters, densities and shapes were placed in the chest simulation phantom from December 2017 to March 2018. The weight of ASIR-V was set at 0%, 20%, 30%, 40% and 50% respectively by using Revolution CT broadband energy spectrum scanning protocol. Spearman correlation analysis was used to analyze the dose volume CT dose index (CTDIvol) and dose length product (DLP) of each group. Scanning data were imported into Tuma Shenwei artificial pulmonary nodule analysis software to evaluate the nature of the detected nodules, and ICC was used to detect the differences among groups.

With the increase of ASIR-V weight, the effective dose of patients decreased gradually. CTDIvol of five groups of radiation dose volume CT dose index was 7.93, 7.24, 5.85, 5.15, 3.76 mGy,dose-length product DLP was 379, 346, 280, 246, 179 mGy·cm.There was a linear negative correlation between ASIR-V weights and CTDIvol as well as DLP, r value was-0.969, P<0.01.There was no significant difference in the detection rate of pulmonary nodules between AI and physicians (P>0.05). There was high intraclass correlation coefficients for the diameter, volume, CT value and malignant percentage of pulmonary nodules (ICCs:0.981-1.000).

Radiation dose of unenhanced chest CT scan using wide detector spectral imaging decreased with the increasing of preset ASIR-V. Lung nodule detection rate and evaluation performance can be maintained well by using ASIR-V reconstructions at lower radiation dosage.

To evaluate the value of Gd-BOPTA enhanced MRI in the staging of liver fibrosis.

Fifty male SD rats (6-week-old, 180-220 g) were divided into the modeling group (n=42) and the control group (n=8). The model of liver fibrosis in the modeling group was established by carbon tetrachloride (animal license No. SYXK (Su) 2017-0043). From week 2 to week 10, rats in the modeling group (n=4) and control group (n=1) were randomly selected to scan 1 h(RER1), 2 h(RER2) and 3 h(RER3) after injection of Gd-BOPTA, respectively, to measure the relative enhancement rate (RER) of liver parenchyma. The shape of intrahepatic bile duct and the degree of enhancement at each time point were observed.

Forty-two rats (34 rats in the modeling group and 8 rats in the control group) completed the experiment. RER1, RER2 and RER3 of the control group were 1.44±0.37, 1.22±0.37 and 0.84±0.28 respectively. RER1, RER2 and RER3 of the modeling group were respectively: S1 (n=6): 1.49±0.48, 1.29±0.39, 0.91±0.38;S2 (n=9): 1.48±0.44, 1.34±0.37, 1.04±0.40;S3 (n=11): 1.49±0.43, 1.37±0.39, 1.21±0.30; S4 (n=8): 1.49±0.44, 1.40±0.37, 1.24±0.40. There was no significant difference in RER1 and RER2 values between the control group and the liver fibrosis group (F=0.022, P=0.999; F=0.301, P=0.875). There were significant differences between the control group and RER3 values of hepatic fibrosis stage S3 and S4 (t=2.249, P=0.031; t=2.274, P=0.029), there was no significant difference between the remaining groups (all P>0.05).In the control group, the intrahepatic bile duct was obviously strengthened within 1 hour after enhancement, and walked naturally. The intrahepatic bile duct was slightly enhanced 1h after the enhancement of S3-S4 stage of hepatic fibrosis, and the intrahepatic bile duct was significantly enhanced 2-3 hours later, with distorted alignment.

Delayed 3 hours liver parenchymal RER and intrahepatic bile duct distortion delay enhancement after Gd-BOPTA enhancement contribute to the S3-S4 diagnosis of liver fibrosis.

To explore the differences in epidemiology and clinical features of Guillain- Barré syndrome (GBS) between rural and urban areas of southern China.

The clinical data of 759 hospitalized GBS patients from 31 hospitals of 13 provinces/cities in southern China, between January 1st, 2013 and September 30th, 2016, were collected and analyzed retrospectively.

The risk of GBS was higher for males than females in rural and urban areas and the median age was 49 and 48 years, respectively. Seasonal clustering in winter and spring was noted in both rural and urban areas, and the seasonal trend was more markedly in rural areas, but the differences showed no statistical significance. There were 70.37% of patients in rural areas and 73.69% in urban areas who had antecedent respiratory infection. The median time from onset to nadir was 7 days, and Hughes Disability Scale at admission, nadir and discharge were (2.95±1.10 vs 2.84±1.15), (3.25±1.11 vs 3.14±1.21), (2.02±1.24 vs 2.00±1.31) in rural and urban areas respectively. Albuminocytologic dissociation was present in 84.34% of patients in rural areas and 84.62% of cases in urban areas. There were 8.65% and 10.94% of cases in rural and urban areas who required mechanical ventilation during hospitalization, respectively. Demyelinating GBS accounted for 53.29% and 48.77%, respectively, in patients with findings of nerve conduction studies available in rural and urban areas.

GBS in rural areas of southern China showed male predominance and a peak of spring and winter occurrence, with respiratory infection as the predominated preceding events and demyelinating GBS being main clinical subtype. Winter and spring showed a higher incidence of GBS in rural and urban areas. There were no significant differences of sex, age, preceding events, season trend, progression of disease, clinical subtypes and cerebrospinal fluid investigations in GBS patients between rural and urban areas.

Due to the changes in the environment during pregnancy and delivery, and the impact on the fetus/baby should be considered, the diagnosis and treatment of stroke during pregnancy and delivery in women is different from that of the general population. This article expounds the types, diagnosis, treatment, primary prevention and secondary prevention of stroke in women during pregnancy and delivery, so as to provide reference for clinical practice.