Volume 103 ·  Issue 15 ·  2023

With advances in sequencing technologies, high-throughput next-generation sequencing (NGS) has triggered increased attention on its application in clinical laboratories and facilitates the molecular diagnosis and treatment of infectious diseases. Compared with conventional microbiology laboratory methods, NGS has greatly increased the sensitivity and accuracy of diagnosis, and reduced detection time for infectious pathogens, especially for diagnosis of complex and mixed infections. However, there are still some problems that hamper the NGS application in infections diagnosis, including lack of standardization, cost, and variation in data interpretation, etc. In recent years, with the developing of policies and legislation, and guidance and supports from Chinese government, the sequencing industry has gained continuously healthy development and sequencing application market gradually becomes mature. Meanwhile, worldwide microbiology experts are striving to develop the standards and reach the consensus, there are more and more clinical laboratories equipped with sequencing instruments and personnel with expertise. All of these measures would certainly promote the clinical application of NGS, and making full use of high-throughput NGS could contribute to the accurate clinical diagnosis and appropriate treatment. The current article describes the application of high-throughput next-generation sequencing technology in the laboratory diagnosis of clinical microbial infectious diseases, as well as the policy system support and development direction.

Early diagnosis remains the key to prevent and control infectious diseases. In recent years, metagenomic next-generation sequencing (mNGS) technology breaks through the limitations of conventional culture methods or targeted molecular detection methods. It improves the diagnosis and treatment level of difficult and rare infectious pathogens through the shotgun high-throughput sequencing to conduct unbiased and rapid detection of microorganisms in clinical samples, which has been widely recognized in clinical practice. Due to the complex detection process of mNGS, there are no uniform specifications and requirements at present. Meanwhile, most laboratories lack of relevant talents at the initial stage of platform establishment, which poses severe challenges to the construction and quality control of the mNGS platform. Based on the practical experience in the construction and operation of the mNGS laboratory of Peking Union Medical College Hospital, the current article summarizes the hardware requirements for the establishment of the mNGS laboratory, the establishment and evaluation methods of the mNGS testing system and the quality assurance after the clinical application, and comprehensively introduces the suggestions for the standardized construction and operation of the mNGS testing platform and quality management system.

The clinical application of metagenomic next-generation sequencing (mNGS) in the diagnosis of unknown pathogenic infections and critical infections has become increasingly valuable. Due to the huge volume of mNGS data and the complexity of clinical diagnosis and treatment, mNGS has difficulties in data analysis and interpretation in practical application. Therefore, in the process of clinical practice, it is crucial to grasp the key points of bioinformatics analysis and establish a standardized bioinformatics analysis process, which is an important step in the transformation of mNGS from laboratory to clinic. At present, bioinformatics analysis of mNGS has made great progress, but with the high requirements of clinical standardization of bioinformatics analysis and the development of computer technology, bioinformatics analysis of mNGS is also facing new challenges. This article mainly elaborates on quality control, and identification and visualization of pathogenic bacteria.

Excessive daytime sleepiness (EDS) afflicts more than 20% of the general population. It not only affects individuals′ performance in many ways, but may even be life-threatening due to potential risks. Currently, there is no comprehensive diagnosis and treatment standard for EDS at home and abroad. To this end, the Chinese Sleep Research Society organized domestic experts in sleep medicine to develop this consensus based on the latest research on EDS. The current consensus elaborates on the definition, epidemiology, clinical manifestations, diagnostic approach, related etiology, evaluation, and treatment of EDS, aiming to provide comprehensive and standardized references and recommendations for the diagnosis and treatment of EDS.

To present efficacy of clinical application of a classification based on crucial curvature of coronal imbalance in degenerative lumbar scoliosis (DLS).

A case series study. Clinical data of 61 cases (8 males, 53 females) who underwent posterior correction surgery for DLS from January 2019 to January 2021 were retrospectively analyzed. The mean age was (71.7±6.2) years (ranged 60-82 years). According to the direction of C₇ plumb line (C₇PL) deviated from central sacral vertical line (CSVL) and orientation of L₄ coronal tilt, the author determined which one was the crucial curve. If C₇PL deviated from CSVL in the same direction as concave side of the thoracolumbar curve and L₄ coronally tilts opposite direction of C₇PL deviates from CSVL, then the crucial curve was thoracolumbar curve (type 1). On the contrary, if C₇PL deviated from CSVL in the same direction as concave side of the lumbosacral curve and L₄ coronally tilts consist with direction of C₇PL deviates from CSVL, then the crucial curve was lumbosacral curve (type 2). According to absolute value of coronal balance distance (|CBD|), each type of patients was divided into two groups, respectively, namely coronal balance (CB) (|CBD|≤3 cm) and coronal imbalance (CIB) (|CBD|>3 cm). Changes of Cobb angles of thoracolumbar curve and lumbosacral curve and CBD were recorded and analyzed.

The rate of preoperative CIB was 55.7% (34/61) in all the patients. Of the patients, 23 cases were classified as type 1 and 38 cases as type 2. The rate of preoperative CIB was 34.8% (8/23) in type 1 patients and 68.4% (26/38) in type 2. The rate of postoperative CIB was 27.9% (17/61) in all the patients, with 13.0% (3/23) in type 1 and 36.8% (14/38) in type 2. The |CBD| of CB group in type 1 patients decreased from (2.6±1.4) cm before the operation to (1.5±1.0) cm after (P=0.015); and the correction rate of thoracolumbar curve (68.8%±18.4%) was significantly higher than that of lumbosacral curve (34.5%±23.9%) (P=0.005). The |CBD| of CB group in type 2 patients decreased from (2.6±3.0) cm before the operation to (1.6±1.2) cm after (P=0.027); the correction rate of lumbosacral curve (71.3%±18.6%) was higher than that of thoracolumbar curve (57.3%±21.1%), but the difference was not statistically significant (P=0.546). There was no significant difference in |CBD| of CIB group in type 2 patients before and after the operation (P=0.222); the correction rate of lumbosacral curve (38.3%±14.8%) was significantly lower than that of thoracolumbar curve (53.6%±16.0%) (P=0.001). There was a correlation between the change of CBD (3.8±1.5) cm and the difference in correction rate between thoracolumbar and lumbosacral curve (32.3%±19.6%) in CB group in type 1 patients after surgery (r=0.904, P<0.001). There was a correlation between the change of CBD (1.9±2.2) cm and the difference in correction rate between lumbosacral and thoracolumbar curve (14.0%±26.2%) in CB group in type 2 patients after surgery (r=0.960, P<0.001).

Clinical application of a classification based on crucial curvature of coronal imbalance in DLS is satisfactory, and its combination with matching correction can effectively prevent the occurrence of coronal imbalance after spinal correction surgery.

To investigate the correlation between serum C-peptide and in adult population, and establish the corresponding insulin values of serum C-peptide levels.

Cross-sectional study. The clinical data of the adults who underwent physical examination in the Second Medical Center of PLA General Hospital from January 2017 to December 2021 were retrospectively included. The participants were divided into type 2 diabetes group, prediabetes group and normal plasma glucose group according to the diagnostic criteria for diabetes. The correlation between serum C-peptide and insulin was explored by Pearson correlation analysis, linear regression analysis, and nonlinear regression analysis, and the corresponding insulin values of serum C-peptide were established.

A total of 48 008 adults were enrolled, including 31 633 males (65.9%) and 16 375 females (34.1%), aged (50.1±9.9) years (18-89 years). There were 8 160 subjects (17.0%) with type 2 diabetes, 13 263 subjects (27.6%) with prediabetes, and 26 585 subjects (55.4%) with normal plasma glucose. The serum fasting C-peptide (FCP, M(Q₁, Q₃)] of the three groups were 2.76(2.18, 3.47), 2.54(1.99, 3.21) and 2.18(1.71, 2.79)μg/L, respectively. The fasting insulin [FINS, M(Q₁,Q₃)] of the three groups were 10.98(7.57, 16.09), 10.06(6.95, 14.47) and 8.43(5.86,12.12)mU/L, respectively. FCP was positively correlated with FINS (r=0.82), and 2 h postprandial C-peptide (2 h CP) was positively correlated with 2 h postprandial insulin (2 h INS) (r=0.84) (both P<0.001). FCP was linearly associated with FINS (R²=0.68), and 2 h CP was linearly associated with 2 h INS (R²=0.71) (both P<0.001). There was a power function correlation between FCP and FINS (R²=0.74), and 2 h CP and 2 h INS (R²=0.78) (both P<0.001). The results of the statistical analysis were similar in various glucose metabolism subgroups. Since the fitting degree of the power function model was higher than that of the linear model, the power function model was the best model. The power function equation was FINS=2.96×FCP^1.32, and 2 h INS=1.64×(2 h CP)^1.60, respectively. Multivariate linear regression analysis demonstrated that FCP was a related factor of FINS (R²=0.70, P<0.001) and 2 h CP was a related factor of 2 h INS (R²=0.73, P<0.001), after adjusting for related confounders.

There was a power function correlation between FCP and FINS, 2 h CP and 2 h INS in adult population. The insulin values corresponding to C-peptide levels were established in the study.

To assess the efficacy and safety of modified Hartel approach in the treatment of primary trigeminal neuralgia with radiofrequency thermocoagulation.

A total of 89 patients with primary trigeminal neuralgia in Nanjing Drum Tower Clinical College of Xuzhou Medical University from July 2021 to July 2022 were prospectively included, and were divided into experimental group (n=45, modified Hartel approach: selecting 2.0 cm lateral to and 1.0 cm below angulus oris as insertion point) and control group (n=44, traditional Hartel approach: selecting 2.5 cm lateral to the angulus oris as insertion point) according to the random number table method. There were 19 males and 26 females in the experimental group, and aged (67.6±8.8) years. Meanwhile, there were 19 males and 25 females in the control group, and aged (64.8±11.7) years. All the patients were treated by CT-guided radiofrequency thermocoagulation. The success rate of one-time puncture, number of punctures, the time of puncture, operation time, numerical rating scale (NRS) scores and complications were recorded and compared between the two groups.

The success rate of one-time puncture in experimental group was 64.4% (29/45), which was higher than that in control group 31.8% (14/44) (P<0.05). The number of punctures [M (Q₁, Q₃)], the time of puncture [M (Q₁, Q₃)] and operation time in the experimental group were 1 (1, 2), 218 (206, 378) s, (19.9±2.7) min, which were less than those of control group [2 (1, 3), 390 (231, 598) s, (27.0±3.9) min] (all P<0.05). The NRS scores [M (Q₁, Q₃)] of 1 day, 1 month and 3 months after surgery in the experimental group were 1 (1, 2), 1 (0, 2) and 1(0, 1), respectively, which were lower than the baseline level [6 (6, 7)] (all P<0.05). The NRS scores [M (Q₁, Q₃)] of 1 day, 1 month and 3 months after surgery in the control group were 1 (1, 2), 1 (0, 2) and 1 (0, 2), respectively, which were lower than the baseline level [6 (6, 7)] (all P<0.05). There was no statistically significant difference in the incidence of nausea and vomiting, facial numbness, and decreased masticatory muscle strength between the two groups (all P>0.05) In the experimental group, two patients had puncture needles into the oral cavity, with timely detection and replacement of puncture needles, and no infection occurred. There was no cerebrospinal fluid leakage and decreased corneal reflex in both groups.

The modified Hartel approach can significantly improve the success rate of one-time puncture via foramen ovale, reduce the operation time and the incidence of postoperative facial swelling, which is a safe and effective puncture method.

To investigate the clinical application value of the modified Lee grading system (abbreviated as the modified system) in evaluating the degree of intervertebral foraminal stenosis(IFS) in patients with foraminal lumbar disc herniations(FLDH).

MRI data of 83 patients with FLDH-IFS (34 patients in the operation group and 49 patients in the conservative group) in Yantai Affiliated Hospital of Binzhou Medical University and Yantai Yantaishan Hospital from March 2018 to February 2021 were retrospectively collected. There were 43 males and 40 females, ranged from 34 to 82 years old, with an average of (61±10) years. MRI images of selected patients were independently evaluated and recorded by two radiologists in a blind method, using both the Lee grading system (abbreviated as Lee system) and the modified system, respectively and each method was evaluated twice. The difference between the evaluation level of the two systems, and the agreement of observer assessments of the two systems were compared, and the correlation between the evaluation level of the two grading systems and the clinical treatment modalities was analyzed.

The percentage of nongrade 3 (grade 0-2) patients with effective conservative treatment according to the two grading systems was 94.6 % (139/147) and 64.2 % (170/265), respectively. The percentage of grade 3 patients requiring surgical treatment according to the two grading systems was 69.2 % (128/185) and 61.2 % (41/67), respectively. There was a statistically significant difference between the evaluation levels of the modified system and the Lee system (Z=-5.16, P=0.001). In the Lee system, the intra-observer observation consistency Kappa values of the two radiologists were 0.735 and 0.542, respectively, which were highly and moderately consistent; and the inter-observer observation consistency Kappa values were 0.426-0.521, which were moderate consistency. In the modified system, the intra-observer consistency Kappa values of the two radiologists were 0.900 and 0.921, respectively, and the consistency was almost completely consistent; and the inter-observer consistency Kappa values were 0.783-0.861, which were highly consistent or almost completely consistent. Lee system and clinical treatment modalities was correlative (r_s=0.39,P<0.001), and modified system and clinical treatment modalities was correlative (r_s=0.61,P<0.001).

According to FLDH-IFS, the modified system can comprehensively and accurately grade, with high reliability and reproducibility. The evaluation level has a more significant correlation with clinical treatment modalities.

To investigate the efficacy of debridement, decompression, interbody fusion and percutaneous screw internal fixation under the unilateral biportal endoscopy (UBE) combined with drug chemotherapy for thoracic and lumbar tuberculosis.

A follow-up study. The clinical data of 9 patients who underwent UBE debridement, decompression, interbody fusion and percutaneous screw internal fixation combined with drug chemotherapy for thoracic and lumbar tuberculosis at the First Affiliated Hospital of Xinjiang Medical University from September 2021 to February 2022 were retrospectively analyzed. There were 4 males and 5 females, aged (52.4±13.5) years (ranged 27-71 years). All patients were given quadruple (isoniazid+rifampicin+pyrazinamide+ethambutol) anti-tuberculosis drugs chemotherapy for 2 to 4 weeks before surgery. The operation time, intraoperative blood loss, postoperative drainage volume, ambulation time, postoperative hospital stay and complications were recorded. The visual analog scale (VAS) of pain, Oswestry disability index (ODI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the patients were compared before and after the surgery. The degree and improvement of spinal cord injury before and after surgery were assessed according to the American Spinal Injury Association (ASIA) neurological classification; and the Cobb angle was measured before and after surgery to assess kyphotic deformity and correction. X-ray or CT was reviewed at 6 months postoperatively and at the final follow-up, and surgical segmental fusion was evaluated using Bridwell grading criteria.

All patients completed the surgery successfully and were followed up for (14.6±1.9) months. The operation time was (182.2±27.5) minutes, the intraoperative blood loss was (222.2±66.7) ml, postoperative drainage volume was (43.3±17.0) ml, the ambulation time was (1.9±0.8) days, postoperative hospital stay was (5.9±1.5) days. Complications occurred in 2 patients (2/9), including 1 case of procedure-related complication. ESR and CRP returned to normal level at the 6-month postoperative follow-up. The VAS score and ODI were significantly improved when compared with those before the operation at each postoperative follow-up time point, and the differences were all statistically significant (all P<0.05). All patients were classified as ASIA grade E at the last follow-up. The postoperative Cobb angle decreased from 14.44°±2.07° to 9.00°±2.29°, and there was no significant loss of angle at the last follow-up. At the 6-month postoperative follow-up, 5 cases (5/9) were classified as Bridwell grade Ⅰ, 2 cases (2/9) as grade Ⅱ, and 1 case (1/9) as grade Ⅲ and Ⅳ, respectively; and all the patients were classified as grade Ⅰ at the last follow-up.

Combined with drug chemotherapy, UBE debridement, decompression, interbody fusion and percutaneous screw internal fixation is a safe, feasible and effective therapy for thoracic and lumbar tuberculosis.

The child was a 6-year-old and July-month-old boy who went to Peking Union Medical College Hospital for "diabetes insipidus reason to be investigated". The child has polydipsia and polyuria since childhood, and the height growth rate has slowed down in the past year. The water ban test and simple desmopressin test support the diagnosis of central diabetes insipidus. Pituitary MRI showed no clear space-occupying lesions. Genetic testing revealed AVP gene mutation, consistent with the diagnosis of hereditary central diabetes insipidus. After the addition of desmopressin replacement therapy, the daily water consumption, urine output and nocturia frequency of children were reduced to normal levels. Hereditary central diabetes insipidus is rare. Patients with central diabetes insipidus who have started since childhood should be alert to the possibility of hereditary diabetes insipidus while actively screening for common causes.

Vulnerable plaque is the main cause of serious cardiovascular adverse events, and effective early identification and intervention can reduce cardiovascular mortality. Magnetic resonance imaging has the advantages of no ionizing radiation, high soft tissue contrast, multi-sequence multi-contrast imaging, etc. It can identify the tissue characteristics of vulnerable plaque, and is an effective tool for non-invasive vulnerable plaque identification. In recent years, the combination of magnetic resonance imaging and molecular targeting technology has further improved the recognition ability of vulnerable plaque inflammatory reaction, thrombosis and other characteristics. This article will briefly review the research progress of conventional magnetic resonance techniques in the evaluation of plaque burden, intraplaque hemorrhage, lipid-rich necrotic core, fibrous cap rupture, and the research and development and application of natural targeting and active targeting magnetic resonance molecular targeting imaging techniques in this field.

C-peptide and insulin are derived from the same precursor, and the function of pancreatic beta cells is often assessed using blood levels of C-peptide. Recent studies have suggested that C-peptide has biological activity, can alleviate hyperglycemia-induced inflammation and reduce the risk of diabetic complications, and has been regarded as a therapeutic strategy to prevent type 1 diabetic vascular disease. However, some studies have shown that elevated C-peptide levels can increase the risk of arteriosclerosis and cardiovascular death in patients with type 2 diabetes and non-diabetic adult populations. The association of C-peptide with cardiovascular disease is not clear and remains controversial. Therefore, the study conducted a two-phase study for patients with a history of type 2 diabetes and people without a history of diabetes. The first phase was a cross-sectional study to analyze the correlation between C peptide levels and cardiovascular markers high-sensitivity troponin T (cTnT) and high-sensitivity C-reactive protein (hs-CRP); The second phase was a retrospective cohort study to analyze the association of C-peptide levels with cardiovascular events. The study used the LOESS method to analyze the optimal cutoff value for C-peptide levels and restriction cubic splines to analyze the hazard ratio for C-peptide. In order to exclude the influence of confounding factors such as insulin and blood glucose levels, the study further used sensitivity analysis for subjects with different levels of blood glucose metabolism and different levels of insulin resistance.

Prolactinoma is the most common pituitary adenoma, mainly occurring in women of childbearing age, and one of its clinical manifestations is abnormal bone metabolism. In previous studies, dual-energy X-ray absorptiometry (DXA) has been used to determine the area bone density (aBMD), but this method can only provide two-dimensional information of bone quality. While high-resolution peripheral quantitative computed tomography (HR-pQCT) provides non-invasive assessment of three-dimensional bone microstructure while providing quantitative information missing from DXA. To evaluate the three-dimensional bone microstructure of patients with prolactinoma and explore its influencing factors, this study enrolled 31 patients with prolactinoma (7 males and 24 females) who attended Peking Union Medical College Hospital from May 2019 to January 2020, and measured multiple bone microstructural parameters of the distal radius and distal tibia and calculated Z-scores by the second-generation HR-pQCT system; Among them, 19 patients also used DXA method to measure the aBMD of lumbar spine and femoral neck; At the same time, for each patient, two healthy subjects with matching age and sex were selected.