Volume 99 ·  Issue 41 ·  2019

Long-term drug therapy in patients with myasthenia gravis leads to imbalances in the gastrointestinal tract, cardiovascular and endocrine systems, as well as damage to microvessels, dysfunction of the neuropsychiatric system, severe infection and bone marrow suppression, etc. Multi-system imbalance hides a mutually causal disease cycle. While maintaining immune homeostasis, we should pay attention to establishing dynamic balance of multi-system functions.

Second-generation sequencing technology is of great significance to the diagnosis and treatment of hematological tumors. In order to scientifically and reasonably apply second-generation sequencing technology to the screening, diagnosis, efficacy monitoring, prognosis evaluation and recurrence prediction of hematological tumors, the project team drafted standardized suggestions suitable for laboratory detection of second-generation sequencing of hematological tumors based on domestic and foreign guidelines and consensus, combined with domestic actual situation, on the basis of repeated discussion and investigation.

The background of molecular cytogenetic and epigenetic modification in hematological malignancies is very complex. Through in-depth research on the molecular biological mechanism of hematological malignancies, the genetic detection system of hematological malignancies can be correctly constructed to achieve more accurate typing and prognosis analysis, and provide a scientific basis for individualized accurate diagnosis and treatment of hematological malignancies.

Fusion genes (FGs) are a common molecular biological abnormality in hematological tumors, and play an important role as an important molecular marker in leukemia typing, prognosis assessment and targeted therapy. The distribution of FGs shows a typical long tail phenomenon, which brings difficulties to clinical research and detection. On the other hand, there is a widespread phenomenon that one gene can form FGs with multiple other partner genes. In order to better generalize and understand the distribution characteristics of FGs in hematological tumors, we proposed the concept of "fusion gene family (FG-FM)". To date, the majority of FGs reported in hematological tumors can be summarized into about 20 FG-FMs. Based on the reported distribution characteristics of FGs, we can speculate that although more and more FGs will be found in the future, the number of FG-FM is limited. FGs of the same family have many similarities in pathogenicity, clinical characteristics and treatment prognosis, and bring new detection ideas. Therefore, classifying FGs by family will help us understand its pathogenic mechanism and optimize the detection protocol.

To determine the factors affecting distribution and magnitude of antibody detection value in myasthenia gravis (MG).

A total of 406 MG patients diagnosed at Department of Neurology, Peking University First Hospital from May 2015 to November 2017 were included.All of them exhibited muscle fatigue with decreased response in repetitive nerve stimulation test. There were 200 males and 206 females whose ages ranged from 2 to 85 years old. According to clinical classification of MG recommended by Myasthenia Gravis Foundation of America (MGFA), patients assigned to class I to class V included 200,140, 46, 15 and 5 cases, respectively. There were 33 cases of thymic hyperplasia and 63 cases of thymoma confirmed by radiological or pathological findings. Quantile plots and quantile regression model were used to determine the effects of age, gender and MGFA classification, thymus disease on acetylcholine receptors (AChR)antibody, acetylcholinesterase (AChE) antibody, Titin antibody, ryanodine receptor (RyR) antibody and muscle-specific tyrosine kinase (MuSK) antibody detection values detected by enzyme-linked immunosorbent assay (ELISA).

MGFA classification had effects on distribution of AChR antibody level. There was a positive correlation between age and AChR antibody level(P<0.05). Negative correlation was found between age and AChE, Titin and RyR antibody level (P<0.05). No significant correlation was shown between any factors and MuSK antibody level(P≥0.05). MGFA classification had a positive correlation with AChR antibody level (P<0.05) and no correlation with other antibody levels (P>0.05). Gender and thymus disease had no correlation with any tested antibody levels (P>0.05).

MGFA classification has significant effects on distribution of AChR antibody level. Age and MGFA classification have positive correlation with AChR antibody level.

To measure the levels of anti-interferon (IFN) -α2 antibody (IFN-α2-Ab) and anti-IFN-ω antibody(IFN-ω-Ab) and investigate their potential roles in patients with myasthenia gravis (MG).

Radioimmunoprecipitationassay (RIPA) based on ¹²⁵I-labelled IFN-α2, -ω, acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) were used to detect anti-IFN-α2-Ab, anti-IFN-ω-Ab, anti-AChR-Ab and anti-MuSK-Ab respectively in MG patients from Tianjin Medical University General Hospital, during the year of 2013. Relationship between IFN-α2-Ab and clinical characteristics in patients with MG were analyzed.

With the RIPA, anti-IFN-α2-Ab was positive in 11 (22%) patients with MG, among whom, 8 were thymoma associated MG (TAMG) and 3 were late onset MG (LOMG). The double positive one was among the LOMG who was a 76-year-old ocular MG patient. Serum anti-IFN-α2-Ab levels in different subgroups of MG had no significant difference (P>0.05). MG patients with anti-IFN-α2-Ab complicated with less other autoimmune disease. Serum anti-IFN-α2-Ab levels negatively correlated with QMG score in TAMG.

MG patients with anti-IFN-α2-Ab complicate with less other autoimmune disease. The higher serum IFN-α2-Ab levels in TAMG, the slighter symptoms present.

To explore the effects of surgical treatment for myasthenia gravis as well as its influencing factors.

A total of 180 patients with myasthenia gravis who underwent thymectomy from August 2012 to September 2018 were enrolled. Clinical data such as age, gender, disease classification, preoperative AChR-Ab, preoperative course, operation time, intraoperative blood loss, and pathological type was retrospectively reviewed. Univariate analysis and Cox regression model were used to analyze possible influencing factors of surgical effects.

A total of 145 patients were finally enrolled and the follow-up period was from 4 to 78 months, with a median follow-up time of 34 months. Thirty-four patients (23.4%) achieved complete stable remission (CSR). The total clinical remission and effective rate reached 75.1% (109 cases) and 89.6% (130 cases), respectively. Correlation analysis showed that age below 45 years old, preoperative course within 12 months, positive AChR-Ab and thymic hyperplasia were clinical influencing factors for better surgical results (P=0.030, 0.048, 0.019 and 0.042, respectively).

It is safe and effective to undergo thymectomy for myasthenia gravis. Age, preoperative course, AChR-Ab level and pathological type were the influencing factors of surgical effects.

To explore the clinical classification and characteristics of patients with alcoholic myocardial injury in the early and late stages, and to improve the understanding of early diagnosis of alcoholic myocardial injury.

From December 2016 to December 2018, a total of 102 patients with long-term history of excessive alcohol consumption, cardiovascular symptoms and evidence of myocardial injury who were admitted to the cardiology outpatient clinic of Hangzhou First People′s Hospital, the Third People′s Hospital of Yuhang, Dajiangdong Hospital, the Second People′s Hospital of Fuyang, and the People′s Hospital of Linan were enrolled. According to diagnostic criteria of alcoholic cardiomyopathy (ACM), the patients were divided into ACM group (36 cases) and non-ACM group (66 cases). The baseline data, electrocardiogram and echocardiography characteristics of the two groups were recorded and analyzed.

There was no significant difference in the baseline between the two groups (P>0.05), including consumption and duration of alcohol. The left ventricular end-diastolic and right ventricular diameters in ACM group were (59±5) mm and (24±4) mm, respectively, which were significantly higher than those in non-ACM group ((51±4)mm, (22±4) mm, P<0.001 and P=0.044) . The left ventricular ejection fraction in ACM group was 41%±4%, which was significantly lower than that of non-ACM group (63%±8%, P<0.001). The incidence of biatrial enlargement in non-ACM group was 57.58%, which was significantly higher than that of ACM group (36.11%, P=0.038). The incidence of atrial fibrillation in non-ACM group was 54.55%, which was significantly higher than that of ACM group (27.78%, P=0.009). The incidence of diastolic heart failure in non-ACM group was significantly higher than that of ACM group (P=0.005).

ACM is characterized by ventricular enlargement, decreased ejection fraction and heart failure, while non-ACM may belong to the early stage of alcoholic myocardial injury, characterized by biatrial expansion, atrial fibrillation and diastolic insufficiency. Due to the lack of understanding and no clinical diagnostic criteria, non-ACM is prone to be missed diagnosed and misdiagnosed.

To measure the length changes of the spine canal of patients with severe kyphosis after treatments of deformity using osteotomy surgeries.

Retrospectively investigated the data of 10 severe kyphosis patients who were treated between August of 2016 and December of 2018 at Beijing Chaoyang Hospital (5 with Ponte and 5 with posterior vertebra column resection (VCR) osteotomy surgeries). For each patient, the full-spine X-Ray images were used to measure Cobb angles before and after the surgery; 3D CT images were used to construct a 3D model of the spine, including the T₂ to L₂ vertebrae and the spine canal. The 3D model was then used to measure the spinal canal lengths (SCLs) between the upper and lower vertebrae (U/LEV) and between T₂-L₂ vertebrae at 5 locations on the spine canal cross section (anterior, central, posterior, left and right locations), and the vertical distance between the T₂ and L₂ vertebrae before and after the surgery. The data were statistically analyzed using t tests.

For the 5 patients of Ponte osteotomy, the Cobb angles were improved by 89°±17°(56%±11%) and 84°±16°(56%±8%) in the coronal and sagittal planes respectively after the surgery. The changes of the SCL between the T₂-L₂ vertebrae were (9.9±4.8) mm and (6.0±12.7) mm, and those were (7.2±5.4) mm and (-0.5±7.9) mm between the U/LEV, respectively at the concave and convex sides of the canal. The vertical distance between the T₂-L₂ vertebrae increased by (66.1±12.0) mm. For the 5 patients with VCR osteotomy, the Cobb angles improved by 83°±19°(60%±10%) and 82°±22°(56%±10%) in the coronal and sagittal planes, respectively. The changes of the SCL between the T₂-L₂ vertebrae were (-5.5±5.3) mm and (-14.0±6.6) mm, and those were (-8.3±8.4) mm and (-20.7±11.6) mm between the U/LEV, respectively at the concave and the convex sides of the canal. The vertical distance between the T₂-L₂ vertebrae increased by (41.5±12.4) mm.

The Ponte osteotomy significantly elongates the SCLs, especially at the concave side, and the VCR osteotomy shortens the spinal canal, resulting in significant compression of the spinal cord at the convex side.

To investigate the clinical outcomes of one-stage posterior correction surgery and second-stage anterior debridement and fusion in treating children with thoracic tuberculosis complicated with kyphoscoliosis.

From January 2008 to December 2014, a total of 17 children with thoracic vertebral tuberculosis complicated with kyphoscoliosis who underwent a one-stage posterior correction and second-stage anterior debridement and complementary fusion were included. There were 8 males and 9 females with an average age of (8±4) years (5-14 years). All patients underwent posterior correction and anterior debridement and bone graft fusion surgery. The neurological function was determined by Frankel grade. The operation time, estimated blood loss (EBL), levels fused and numbers of screws were recorded. The following radiographic parameters were measured: Cobb angle of the coronal curve, regional kyphosis and sagittal vertical axis (SVA). The incidence of intraoperative and postoperative complications was recorded. The data before and after the operation were compared with paired sample t test.

The tuberculosis lesions located in the thoracic vertebrae, and the abscess involved 2 to 4 vertebral segments. The average operation time was (4.1±0.8) h, the EBL was (526±275) ml, the levels fused were 7.6±2.3, and 173 pedicle screws were placed. The preoperative coronal curve averaged 12.6°±6.2°, and it was corrected to 4.2°±1.9° postoperatively (t=4.628, P<0.01), the regional kyphosis was 67.2°±19.4°, and it was corrected to 15.7°±8.2° postoperatively (t=8.192, P<0.01). The SVA improved from (8.1±5.0) mm to (3.0±1.7) mm postoperatively. The mean duration of follow-up for all the patients were (38±11) months. At final follow-up, SVA was reduced to (2.4±2.0) mm and the other parameter kept stable. Thirteen patients had more than one grade improvement of Frankel grade. The VAS score for all patients improved from 4.7±2.8 to 2.2±0.5 postoperatively (t=3.973, P=0.01), and improved to 0.5±0.5 at final follow-up (t=-7.880, P<0.01). No recurrence of primary spinal tuberculosis was seen at final follow-up of all patients.

One-stage posterior correction and second-stage anterior complementary debridement and fusion is an effective procedure for children with thoracic tuberculosis complicated with kyphoscoliosis. Significant postoperative deformity correction could be achieved with satisfactory improvement of neurological function. Solid fusion and satisfactory correction maintenance were observed at mid-to long-term follow-up.

To explore whether exercise could influence outcomes and improve life quality of patients with knee osteoarthritis.

This study included 210 patients diagnosed with knee osteoarthritis from October to December 2018 in Shijiazhuang Derui Exercise Rehabilitation Medical Center. These patients were divided into two groups with random number table: experiment and control group. Patients in experimental group got exercise rehabilitation training and routine therapy,but patients in control group got routine treatment only that included physical therapy and non-steroidal anti-inflammatory drugs (NSAIDs). We applied different kinds of measure to follow-up these patients,which included Lysholm scale, the Western Ontario and McMaster Osteoarthritis Index (WOMAC), SF-36 life quality questionnaire, and knee range of motion.The degree of pain and symptoms and the knee function and the quality of life in the two groups were recorded too. Paired sample t test was used to compare the data between the two groups.

There were 105 patients in each group, but 13 cases (12.4%) in experimental group and 6 patients (5.7%) in control group were lost,respectively.All the patients were followed up for (12.0±2.3) weeks. There was no significant differences in age, body mass index, gender between the two groups. At the final follow-up, the WOMAC score in the experiment group was 84.4±6.8, and it was 108.3±1.7 in the control group (t=-4.71, P<0.05);the Lysholm score of the experimental group was 65.5±4.7, and it was 41.2±1.4 in the control group (t=7.29, P<0.05); the knee range of motion in the experiment group and control group was 121°±7° and 114°±3°, respectively (t=1.83, P<0.05); the SF-36 score in the two groups was 90.0±2.8 and 75.6±1.5, respectively (t=6.15, P<0.05).

Exercise rehabilitation plus routine therapy for patients with knee osteoarthritis can effectively improve outcome, promote functional recovery and improve quality of life.

To compare the dosimetric parameters of three different modern radiation techniques in radical radiotherapy for esophageal cancer.

A total of 25 patients with pathologically confirmed esophageal squamous cell carcinoma in Zhejiang Cancer Hospital were included from September 2015 to May 2016 and three radiation treatment plans for helical tomotherapy (TOMO), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) were designed respectively for each patient. Study patients included 24 males and 1 female,aged from 47 to 82 years old, with a median age of 63 years old. All patients received the total prescription dose of 60 Gy in 30 fractions to the planning target volume (PTV). Conformity index (CI), heterogeneity index (HI), D₁, D₂, D₅₀, D₉₅, D₉₈, D₉9 and V₉₅, V₁₀₀, V₁₀₅ of PTV was calculated. The mean dose, V₅, V₁₀, V₂₀, V₃₀, V₄₀ and V₅₀ of total lung, heart, and maximum dose (D_max) to spinal cord were recorded as well.

Compared with TOMO and IMRT, VMAT showed higher CI (0.81±0.08) and lower HI (0.10±0.05), and CI was worse in IMRT (0.77±0.05) than TOMO (0.79±0.04) (t=2.604, P=0.016) and VMAT (t=2.817, P=0.010). There was no significant difference in HI among three radiation techniques. The dosimetric parameters of TOMO in normal lung were significantly better than those of VMAT and IMRT, especially in V₂₀ and V₃₀. The D_max of spinal cord (38.24±3.72) Gy in TOMO was significantly lower than that of the VMAT ((39.88±3.27)Gy, t=-3.173, P=0.004) and IMRT plan ((41.09±3.18)Gy, t=-5.559, P=0.000). Subgroup analysis showed that VMAT was superior to TOMO and IMRT in CI and HI, especially HI (0.09±0.01) significantly better than TOMO (0.12±0.03, t=3.024, P=0.029) and IMRT (0.12±0.02, t=-3.800, P=0.013) for patients with cervical and upper thoracic esophageal cancer. TOMO and VMAT were significantly better than IMRT in MLD, lung V₂₀ and V₃₀ (all P<0.05). TOMO (38.46±2.15)Gy was significantly superior to VMAT ((41.02±1.28)Gy,t=-2.701, P=0.043) and IMRT ((41.76±1.11)Gy, t=-3.111, P=0.027) at D_max of the spinal cord. For the patients with middle and lower thoracic esophageal cancer, TOMO, VMAT and IMRT had no statistically significant differences in CI and HI. IMRT was inferior to TOMO and VMAT in MLD, lung V₁₀, V₂₀, and V₃₀ (all P<0.05). TOMO (38.17±4.14) Gy was significantly superior to VMAT ((39.52±3.64)Gy,t=-2.219, P=0.040) and IMRT ((40.87±3.59)Gy,t=-4.528, P=0.000) at D_max of the spinal cord.

The VMAT plan is better than TOMO and IMRT in terms of the conformal degree and dose uniformity of the target volume.TOMO seems significantly better than VMAT and IMRT in protecting normal tissue.

To observe the difference of brain activity in patients with diarrhea-type irritable bowel syndrome (IBS-D) treated with pinaverium bromide (PB) combined with flupentixol-melitracen (FM), and to explore the mechanism of efficacy of combined with anxiolytic/antidepressant drugs in IBS-D patients at the central level, using resting-state functional magnetic resonance imaging (rs-fMRI).

Forty-eight patients with IBS-D, including 28 males, 20 females, mean age 22-48 (33±7) years, were selected from the Affiliated Hospital of Hangzhou Normal University from October 2015 to October 2018.All patients with IBS-D underwent rs-fMRI scans before and after receiving either PB (basic treatment group, n=16), PB combined with FM (combination therapy group, n=16), or no medication (no treatment group, n=16). Rs-fMRI regional homogeneity (ReHo) parameter among the three groups of patients were compared using One-way ANOVA analysis and post analysis.Partial correlation and mediation analyses were performed on ReHo values and the improvement of symptoms scores (gastrointestinal symptom rating scale(GSRS) and hospital anxiety/depression scale (HAD)) in the two medicated groups.

No significant differences in ReHo values were observed among the three groups before treatment. Compared with patients on no-medication, patients receiving either PB or PB-FM showed decreased ReHo in the striatum, insular lobe, medial prefrontal cortex (MPFC) and subcallosal gyrus, and increased ReHo in the occipital cortex. In particular, the combined treatment group showed more extensive decreased ReHo in the left thalamus and left temporal pole, and increased in the left precuneus. Compared with the basic treatment group, the combined treatment group showed decreased ReHo in the right putamen, right insula, right MPFC and subcallosal gyrus, and increased ReHo in the left precuneus. In addition, the combined treatment group demonstrated a positive correlation between ReHo values in the left thalamus and the improvement of HAD score (r=0.653, P=0.011) , and a negative correlation between ReHo values in left precuneus and the improvement of GSRS and HAD score (r=-0.771, P=0.001; r=-0.716, P=0.004). ReHo values in the left precuneus were observed to mediate between gastrointestinal symptoms and anxiety-depressive symptoms in the combined treatment group.

The efficacy of PB combined with FM is superior to PB alone in the treatment of IBS. In addition to more extensive changes in pain-related brain areas, IBS-D patients treated with anxiolytic/antidepressant also show changes in default network and brain areas related to emotional regulation, and are associated with improvement in gastrointestinal symptoms, anxiety and depression.

Q fever is a natural epidemic disease caused by infection with Coxiella Burnetti. After infection with Coxia burnetii, 1% to 5% of patients develop chronic Q-fever infection, and about 75% of them present with blood culture-negative endocarditis. Chronic Q fever infection has not been effectively treated, and the mortality rate is high. This article reports a patient with intermittent fever, fatigue and severe anemia as the main manifestations. Combined with previous heart valve replacement, it is highly suspected that infectious endocarditis may be possible. However, the diagnosis was difficult due to multiple negative blood cultures and no definite valve neoplasms found in transesophageal echocardiography. Finally, the diagnosis was confirmed by positive Q-fever antibody test. It is hoped that this case will deepen clinicians' understanding of chronic Q fever infection complicated with endocarditis.

A 46-year-old woman was admitted to the hospital with sudden middle and upper abdominal pain accompanied by nausea and vomiting for 1 h. Abdominal CT showed that the left lateral lobe of the liver occupied space, and there were multiple hamartomas in the liver and kidneys. Further examination was recommended to rule out the possibility of tuberous sclerosis (TSC). Later, chest CT and brain magnetic resonance examination showed multiple nodules and vesicles in both lungs and multiple nodules in the lateral ventricles. Liver puncture biopsy and transcatheter vascular embolization were performed. Pathological diagnosis: perivascular epithelioid cell tumor (left lateral lobe of the liver).

Seminoma is the most common tumor of the testis, which is common in young and middle-aged men. About 1% to 2% of seminomas occur outside the gonads. Among them, mediastinum and retroperitoneum are the most common sites of adult extragonadal seminoma, but it is rare to occur in women. This case of seminoma occurred in the retroperitoneum of female children, and it was rarely reported in relevant literature.