2018年 · 第131卷第23期

Idiopathic inflammatory myopathies (IIMs) are heterogeneous disorders characterized by chronic muscle weakness and muscle fatigue and mononuclear cell infiltration into skeletal muscle.^[1]The most common subgroups in adults are dermatomyositis (DM), polymyositis (PM), amyopathic DM (ADM), inclusion body myositis (IBM), and juvenile DM (JDM). Several diagnostic or classification criteria for IIM have been developed.^[2,3,4,5]Classification criteria are mostly used in research and clinical trials, not daily in practice. Great efforts have been dedicated in pursuing new criteria in the past decades.

Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study.

TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54).

Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (−71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning.

Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China.

ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1

Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared.

Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups.

The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of −0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition.

The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability.

Clinicaltrials.gov, NCT02525497; https://clinicaltrials.gov/ct2/results?cond=&term=NCT02525497&cntry=& state=&city=&dist=.

Hyperphosphatemia is a risk factor associated with mortality in patients on maintenance hemodialysis. Gut absorption of phosphate is the major source. Recent studies indicated that the intestinal flora of uremic patients changed a lot compared with the healthy population, and phosphorus is an essential element of bacterial survival and reproduction. The purpose of this study was to explore the role of intestinal microbiota in phosphorus metabolism.

A prospective self-control study was performed from October 2015 to January 2016. Microbial DNA was isolated from the stools of 20 healthy controls and 21 maintenance hemodialysis patients. Fourteen out of the 21 patients were treated with lanthanum carbonate for 12 weeks. Thus, stools were also collected before and after the treatment. The bacterial composition was analyzed based on 16S ribosomal RNA pyrosequencing. Bioinformatics tools, including sequence alignment, abundance profiling, and taxonomic diversity, were used in microbiome data analyses. Correlations between genera and the serum phosphorus were detected with Pearson’s correlation. For visualization of the internal interactions and further measurement of the microbial community, SparCC was used to calculate the Spearman correlation coefficient with the corresponding P value between each two genera.

Thirteen genera closely correlated with serum phosphorus and the correlation coefficient was above 0.4 (P < 0.05). We also found that 58 bacterial operational taxonomic units (OTUs) were significantly different and more decreased OTUs were identified and seven genera (P < 0.05) were obviously reduced after using the phosphate binder. Meanwhile, the microbial richness and diversity presented downward trend in hemodialysis patients compared with healthy controls and more downward trend after phosphorus reduction. The co-occurrence network of genera revealed that the network complexity of hemodialysis patients was significantly higher than that of controls, whereas treatment with lanthanum carbonate reduced the network complexity.

Gut flora related to phosphorus metabolism in hemodialysis patients, and improving intestinal microbiota may regulate the absorption of phosphate in the intestine. The use of phosphate binder lanthanum carbonate leads to a tendency of decreasing microbial diversity and lower network complexity.

Neural respiratory drive (NRD) using diaphragm electromyography through an invasive transesophageal multi-electrode catheter can be used as a feasible clinical physiological parameter in patients with chronic obstructive pulmonary disease (COPD) to provide useful information on the treatment response. However, it remains unknown whether the surface diaphragm electromyogram (EMGdi) could be used to identify the deterioration of clinical symptoms and to predict the necessity of hospitalization in acute exacerbation of COPD (AECOPD) patients.

COPD patients visiting the outpatient department due to acute exacerbation were enrolled in this study. All patients who were subjected to EMGdi and classical parameters such as spirometry parameters, arterial blood gas analysis, COPD assessment test (CAT) score, and the modified early warning score (MEWS) in outpatient department, would be treated effectively in the outpatient or inpatient settings according to the Global Initiative for Chronic Obstructive Lung Disease guideline. When the acute exacerbation of the patients was managed, all the examination above would be repeated.

We compared the relationships of admission-to-discharge changes (Δ) in the normalized value of the EMGdi, including the change of the percentage of maximal EMGdi (ΔEMGdi%max) and the change of the ratio of minute ventilation to the percentage of maximal EMGdi (ΔVE/EMGdi%max) with the changes of classical parameters. There was a significant positive association between ΔEMGdi%max and ΔCAT, ΔPaCO₂, and ΔpH. The change (Δ) of EMGdi%max was negatively correlated with ΔPaO₂/FiO₂ in the course of the treatment of AECOPD. Compared with the classical parameters including forced expiratory volume in 1 s, MEWS, PaO₂/FiO₂, the EMGdi%max (odds ratio 1.143, 95% confidence interval 1.004–1.300) has a higher sensitivity when detecting the early exacerbation and enables to predict the admission of hospital in the whole cohort.

The changes of surface EMGdi parameters had a direct correlation with classical measures in the whole cohort of AECOPD. The measurement of NRD by surface EMGdi represents a practical physiological biomarker, which may be helpful in detecting patients who should be hospitalized timely.

Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).

We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT.

In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ² = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ² = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ² = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ² = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200–2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168–2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528–3.627, P < 0.001).

Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.

Glucocorticoid (GC) is the first-line therapy for asthma, but some asthmatics are insensitive to it. Glucocorticoid-induced transcript 1 gene (GLCCI1) is reported to be associated with GCs efficiency in asthmatics, while its exact mechanism remains unknown.

A total of 30 asthmatic patients received fluticasone propionate for 12 weeks. Forced expiratory volume in 1 s (FEV₁) and GLCCI1 expression were detected. Asthma model was constructed in wild-type and GLCCI1 knockout (GLCCI1^-/-) mice. Glucocorticoid receptor (GR) and mitogen-activated protein kinase phosphatase 1 (MKP-1) expression were detected by polymerase chain reaction and Western blotting (WB). The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also detected by WB.

In asthmatic patients, the change of FEV₁ was well positively correlated with change of GLCCI1 expression (r = 0.430, P = 0.022). In animal experiment, GR and MKP-1 mRNA levels were significantly decreased in asthmatic mice than in control mice (wild-type: GR: 0.769 vs. 1.000, P = 0.022; MKP-1: 0.493 vs. 1.000, P < 0.001. GLCCI1^-/-: GR: 0.629 vs. 1.645, P < 0.001; MKP-1: 0.377 vs. 2.146, P < 0.001). Hydroprednisone treatment significantly increased GR and MKP-1 mRNA expression levels than in asthmatic groups; however, GLCCI1^-/- asthmatic mice had less improvement (wild-type: GR: 1.517 vs. 0.769, P = 0.023; MKP-1: 1.036 vs. 0.493, P = 0.003. GLCCI1^-/-: GR: 0.846 vs. 0.629, P = 0.116; MKP-1: 0.475 vs. 0.377, P = 0.388). GLCCI1^-/- asthmatic mice had more obvious phosphorylation of p38 MAPK than wild-type asthmatic mice (9.060 vs. 3.484, P < 0.001). It was still higher even though after hydroprednisone treatment (6.440 vs. 2.630, P < 0.001).

GLCCI1 deficiency in asthmatic mice inhibits the activation of GR and MKP-1 and leads to more obvious phosphorylation of p38 MAPK, leading to a decremental sensitivity to GCs.

ChiCTR.org.cn, ChiCTR-RCC-13003634; http://www.chictr.org.cn/showproj.aspx?proj=5926.

DNA replication and sister chromatid cohesion 1 (DSCC1) (also called DCC1) is a component of an alternative replication factor C complex that loads proliferating cell nuclear antigen onto DNA during S phase of the cell cycle. It is located at 8q24 and frequently amplified in hepatocellular carcinoma (HCC). However, the role of DSCC1 in the carcinogenesis and progress of HCC has not been fully investigated. Here, we aimed to assert the importance of DSCC1 in the HCC.

In this study, copy number variation data and RNA sequencing data were used to calculate the DNA copy number and mRNA expression of DSCC1 in HCC. Quantitative polymerase chain reaction, Western blotting, and immunohistochemistry analysis were used to determine the mRNA and protein level of DSCC1 in HCC. The Kaplan–Meier analysis and univariate and multivariate Cox regression analysis were used to assess the association of DSCC1 with the overall survival (OS) of HCC patients. Moreover, lentiviral shRNA was used to knockdown DSCC1, and then, colony-forming assay, cell cycle assay, and cell proliferation assay were performed to evaluate the impact of DSCC1 silencing on HCC cell lines.

We found that DSCC1 was amplified and highly expressed in HCC tumor tissues than in nontumor tissues. We then found that the overexpression of both mRNA and protein of DSCC1 was linked to the bad prognosis of HCC patients. Astonishingly, the protein level of DSCC1 was an independent prognostic factor for OS (hazard ratio, 1.79; 95% confidence interval, 1.17–2.74; P = 0.007). Furthermore, the clonogenic capacity of DSCC1-amplified HCC cell lines (MHCC-97H, MHCC-97L, and Hep3B) was significantly inhibited by transduction of a lentiviral shRNA that targets DSCC1. We also showed that knockdown of DSCC1 induced G0–G1 cell cycle arrest (increased from 60% to more than 80%) and greatly inhibited the proliferation of HCC cell lines.

These results suggest that DSCC1 is a putative HCC driver gene that promotes proliferation and is associated with poor prognosis in HCC.

The demonstrated role of mitogen-activated protein kinase (MAPK) in both cell apoptosis and the inflammation pathway makes it an attractive target for photoreceptor protection. The aim of this study was to investigate the protective effects of MAPK antagonists against photoreceptor degeneration and retinal inflammation in a rat model of light-induced retinal degeneration.

Sprague Dawley rats were treated with intravitreal injections of MAPK antagonists, inhibitors of p-P38, phosphorylated-extracellular regulated kinase (p-ERK) 1/2, and p-c-Jun N-terminal kinase (JNK) just before they were assigned to dark adaptation. After dark adaptation for 24 h, rats were exposed to blue light (2500 lux) in a light box for 24 h, and then returned to the normal 12-h light/12-h dark cycle. Samples were collected at different time points. MAPK expression during light exposure was examined with immunofluorescence. Photoreceptor death was detected with histopathology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of retinal p-ERK1/2, caspase 3, activated caspase 3, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β was examined by Western blotting. Differences between groups were evaluated using unpaired one-way analysis of variance and least significant difference post hoc tests.

MAPKs (P38, ERK1/2, and p-JNK) were phosphorylated and activated in the light injury groups, compared with normal group, and their expressions were mainly elevated in the outer nuclear layer (ONL). Among the selected MAPK antagonists, only the p-ERK1/2 inhibitor attenuated the loss of photoreceptors and the thinning of ONL in light injury groups. Besides, p-ERK1/2 inhibitor refrained light-induced photoreceptor apoptosis, which was presented by TUNEL positive cells. Light injury significantly increased the expression of p-ERK1/2 (1.12 ± 0.06 vs. 0.57 ± 0.08, t = 9.99, P < 0.05; 1.23 ± 0.03 vs. 0.57 ± 0.08, t = 11.90, P < 0.05; and 1.12 ± 0.12 vs. 0.57 ± 0.08, t = 9.86, P < 0.05; F = 49.55, P < 0.001), and induced caspase 3 activating (0.63 ± 0.06 vs. 0.14 ± 0.05, t = 13.67, P < 0.05; 0.74 ± 0.05 vs. 0.14 ± 0.05, t = 16.87, P < 0.05; and 0.80 ± 0.05 vs. 0.14 ± 0.05, t = 18.57, P < 0.05; F = 100.15, P < 0.001), compared with normal group. The p-ERK1/2 inhibitor significantly reduced p-ERK1/2 overexpression (0.61 ± 0.06 vs. 1.12 ± 0.06, t = −9.26, P < 0.05; 0.77 ± 0.06 vs. 1.23 ± 0.03, t = −8.29, P < 0.05; and 0.68 ± 0.03 vs. 1.12 ± 0.12, t = −7.83, P < 0.05; F = 49.55, P < 0.001) and downregulated caspase 3 activating (0.23 ± 0.04 vs. 0.63 ± 0.06, t = −11.24, P < 0.05; 0.43 ± 0.03 vs. 0.74 ± 0.05, t = −8.86, P < 0.05; and 0.58 ± 0.03 vs. 0.80 ± 0.05, t = −6.17, P < 0.05; F = 100.15, P < 0.001), compared with light injury group. No significant change in the total level of caspase 3 was seen in different groups (F = 0.56, P = 0.75). As for inflammation, light injury significantly increased the expression of TNF-α (0.42 ± 0.04 vs. 0.25 ± 0.05, t = 5.99, P < 0.05; 0.65 ± 0.03 vs. 0.25 ± 0.05, t = 14.87, P < 0.05; and 0.86 ± 0.04 vs. 0.25 ± 0.05, t = 22.58, P < 0.05; F = 160.27, P < 0.001) and IL-1β (0.24 ± 0.01 vs. 0.19 ± 0.02, t = 2.33, P < 0.05; 0.35 ± 0.02 vs. 0.19 ± 0.02, t = 7.97, P < 0.05; and 0.48 ± 0.04 vs. 0.19 ± 0.02, t = 14.69, P < 0.05; F = 77.29, P < 0.001), compared with normal group. P-ERK1/2 inhibitor significantly decreased the overexpression of TNF-α (0.22 ± 0.02 vs. 0.42 ± 0.04, t = −7.40, P < 0.05; 0.27 ± 0.02 vs. 0.65 ± 0.03, t = −14.27, P < 0.05; and 0.33 ± 0.03 vs. 0.86 ± 0.04, t = −19.58, P < 0.05; F = 160.27, P < 0.001) and IL-1β (0.13 ± 0.03 vs. 0.24 ± 0.01, t = −5.77, P < 0.05; 0.17 ± 0.01 vs. 0.22 ± 0.02, t = −9.18, P < 0.05; and 0.76 ± 0.05 vs. 0.48 ± 0.04, t = −13.12, P < 0.05; F = 77.29, P < 0.001), compared with light injury group.

The p-ERK1/2 inhibitor might protect the retina from light-induced photoreceptor degeneration and retinal inflammation.

Systemic lupus erythematosus (SLE) is an autoimmune disease under genetic control. Growing evidences support the genetic predisposition of HLA-DRB1 gene polymorphisms to SLE, yet the results are not often reproducible. The purpose of this study was to assess the association of two polymorphisms of HLA-DRB1 gene (HLA-DR3 and HLA-DR15) with the risk of SLE via a comprehensive meta-analysis.

This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Case-control studies on HLA-DRB1 and SLE were searched from PubMed, Elsevier Science, Springer Link, Medline, and Cochrane Library database as of June 2018. Analysis was based on the random-effects model using STATA software version 14.0.

A total of 23 studies were retained for analysis, including 5261 cases and 9838 controls. Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]: 1.60, 95% confidence interval (CI): 1.316–1.934, P = 0.129 and OR: 1.68, 95% CI: 1.334–2.112, P = 0.001, respectively). Subgroup analyses demonstrated that for both HLA-DR3 and HLA-DR15 polymorphisms, ethnicity was a possible source of heterogeneity. Specifically, HLA-DR3 polymorphism was not associated with SLE in White populations (OR: 1.60, 95% CI: 1.320–1.960, P = 0.522) and HLA-DR15 polymorphism in East Asian populations (OR: 1.65, 95% CI: 1.248–2.173, P = 0.001). In addition, source of control was another possible source for both HLA-DR3 and HLA-DR15 polymorphisms, with observable significance for HLA-DR3 in only population-based studies (OR: 1.65, 95% CI: 1.370–1.990, P = 0.244) and for HLA-DR15 in both population-based and hospital-based studies (OR: 1.38, 95% CI: 1.078–1.760, P = 0.123 and OR: 2.08, 95% CI: 1.738–2.490, P = 0.881, respectively).

HLA-DRB1 gene may be a SLE-susceptibility gene, and it shows evident ethnic heterogeneity. Further prospective validations across multiple ethnical groups are warranted.

In previous decades, glaucoma has been primarily attributed to elevated intraocular pressure (IOP), but this has gradually been replaced by the development of optic neuropathy as the central concept of glaucoma in developed countries. However, there still remain strong controversies in the definition of glaucoma in China. In this current review, we are going to discuss these controversies and elaborate on the historical transitions of the definition of glaucoma both in China and developed countries. Furthermore, we will briefly describe the "ocular-cranial pressure gradient" theory and discuss the relationship between glaucoma and degenerative diseases of the central nervous system (CNS) in order to show the complex pathogenesis of glaucoma and the importance for the modification to the definition of glaucoma.

We performed a comprehensive search in both PubMed and SinoMed using the following keywords: (a) "primary glaucoma" and "guideline," (b) "ocular-cranial pressure gradient," and (c) "glaucoma," "Alzheimer’s disease," and "Parkinson’s disease." The literature search included the related articles with no restrictions on publication date.

The primary references were Chinese and English articles including (a) original guidelines and expert consensuses of primary glaucoma, (b) reviews focusing on the differences between various versions of these guidelines and consensuses, and (c) papers about ocular-cranial pressure gradient theory and the relationship between glaucoma and CNS degenerative diseases.

The definitions and classifications of both primary open-angle glaucoma and primary angle-closure glaucoma differ between Chinese glaucoma consensuses and international primary glaucoma guidelines. Chinese definitions and classifications put more emphasis on the IOP, while international guidelines put more emphasis on the presence of optic neuropathy. The ocular-cranial pressure gradient theory and the research on the relationship between glaucoma and CNS degenerative diseases have provided new directions for exploring the pathogenesis of glaucoma.

As regards the definition and classification of primary glaucoma, we find that there are still some discrepancies between Chinese expert consensuses and international guidelines. Glaucoma is a disease with complex etiologies, while its common characteristic is a specific optic neuropathy. The current definition and understanding of glaucoma is an ongoing and evolving process, reflecting our latest available evidence on its pathogenesis. Chinese ophthalmology community may need to update our guidelines, accommodating these latest developments.

To the Editor: A 27-year-old Chinese man presented to the hospital complaining of red nodules on the chest and back that gradually enlarged with spiking fever up to 39°C. He had nodular panniculitis when he was 21 years old. The family history was silent. Physical examination on admission revealed skin pigmentation, skin nodules (four, 2 cm × 2 cm, without movement and tenderness), and red rash without pain and pruritus over the body. Laboratory tests showed pancytopenia, especially for white blood cell (WBC) and platelet (PLT), raised triglycerides (TGs) and ferritin levels, liver enzyme abnormalities, decreased albumin value, and deranged coagulation profile. Other autoantibody profile including antinuclear antibody and anti-cyclic citrullinated peptides and thyroid function tests showed no abnormity. Ultrasound suggested splenomegaly and hepatic calcification. Chest high-resolution computed tomography indicated ground-glass opacities on the right upper lobe of the lung, in line with pericardial and pleural effusion, and increased number of bilateral enlarged axillary lymph nodes. Biopsy of skin nodules and subcutaneous tissue showed septal and lobular fibroplasia and lymphocytic infiltration within the lobular septa and around the skin appendages [Figure 1]. The result was manifested as nodular panniculitis. Bone marrow aspiration suggested proliferation of hematopoietic cells. The patient met the classification criteria and was diagnosed as nodular panniculitis.^[1]In addition, he was diagnosed as hemophagocytic lymphohistiocytosis (HLH) according to the 2004 HLH Trial Guideline (raised TG and ferritin levels, decreased WBC and PLT counts, and low fibrinogen, fever, and splenomegaly).^[2]

To the Editor: Pediatric stroke refers to the rupture and/or occlusion of arteries or veins. It is one of the highest causes of pediatric preterm death and long-term disability. Health-care providers find dealing with pediatric stroke a challenge because of the difficult diagnosis, the lack of standard guidelines, the rapid progress, and the high mortality. In this study, we observed and analyzed the characteristics of six pediatric hemorrhage strokes complicated with interventions for congenital heart disease (CHD). We found that vascular malformation, hemodynamic fluctuation, and postoperative anticoagulant medicines were risk factors for this condition and that there was an urgent need for awareness and acknowledgment.

To the Editor: Catecholaminergic polymorphic ventricular tachycardia (CPVT) often occurs in children or adolescents without organic heart diseases. It is a rare malignant arrhythmic disorder with hereditary features characterized by exercise- or emotional stress-induced ventricular arrhythmias, especially bidirectional/polymorphic ventricular tachycardia (VT), syncope, or sudden death.^[1]The mortality rate of symptomatic CPVT patients before 30 years of age is 31%,^[2]and an early treatment with beta-blockers could effectively improve their prognosis.^[3]Therefore, getting a confirmed diagnosis of CPVT in time is of utmost importance. On this context, this study summarizes the clinical characteristics and diagnosis of pediatric cases with CPVT. This study was approved by the Ethics Committee of The First Hospital of Tsinghua University (No. HX200901) and was conducted in accordance with the 1964Declaration of Helsinki.

To the Editor: Alcohol dependence is a severe mental disorder that can have devastating physical and psychological impacts on patients. Alcohol dependence is reported to be one of the leading causes of death among people aged between 15 and 49 years.^[1]Thus, comprehensive interventions are important for reducing mortality and disability among patients with alcohol dependence.^[2]

To the Editor: In the last recent years, significant progress has been achieved in research on dysphagia. This is important because approximately 50% of patients with dysphagia after acute stroke still have a slow functional recovery, and the duration of disease may last for several months or the whole life. The ultimate aim of dysphagia treatment is for patients to be able to eat again and to examine if the influence of eating conditions is inevitable in dysphagia research. Changes in the peripheral afferent nervous system related to eating, such as alimentary bolus characters and eating postures, can result in adjustments of swallowing by afferent pathways of the central nervous network, followed by corresponding changes in the time sequence, duration, and intensity of oropharyngeal muscle activities. Therapists often choose alimentary bolus according to their own experience with direct ingestion training, without quantitative evaluation of swallowing muscle group activities. To explore the influence of alimentary bolus viscosity changes on swallowing physiology, and study the relationship with swallowing muscle group activities and the role in the mechanism of dysphagia, the surface electromyographic (SEMG) technique was used in this study to observe the characteristics of muscle group activity real timely, dynamically, and synchronously.

To the Editor: Pituitary disease is a group of pituitary gland disorders, including pituitary adenoma and other lesions, in the sellar region.^[1]Typical endocrine symptoms and mass effects are likely to have harmful results on patients, families, and society. Pituitary databases of various sizes and focuses have been established in the USA and Europe.^[2,3,4]The vast territory, unbalanced economic development, uneven medical access, bias in awareness of the disease, and unsatisfactory data collection techniques have seriously affected the prognosis of patients with pituitary disease in China.^[2]The China Pituitary Disease Register Network (CPDRN) was established in 2015 as the first multicenter, nationwide pituitary disease registry in China, aiming to resolve the abovementioned problems.^[5]This article describes the establishment process and demographic baseline of the CPDRN.

To the Editor: Clinical symptom spectrum of paroxysmal nocturnal hemoglobinuria (PNH) is consisted of chronic intravascular hemolysis, hemoglobinuria, relative bone marrow failure, and the rarity of thrombosis.^[1]The neurological complications generated by PNH were almost exclusively a result of cerebral venous thrombosis.^[1,2,3]However, moyamoya syndrome (MMS) secondary to PNH (PNH-MMS) is rarely described in the literature.^[2,3,4,5]We report herein a case of PNH-MMS to raise the awareness of this disease in PNH patients presenting with acute neurological deficits.

To the Editor: Adult granulosa cell tumor (AGCT) of the ovary is a low-grade malignant, sex cord-stromal tumor with an indolent course and late recurrence. Recurrences usually occur more than 5 years after the first treatment.^[1]However, a few cases of aggressive AGCT have been reported.^[2,3]We retrospectively reviewed all 213 AGCT patients at Peking Union Medical College Hospital between 2000 and 2018 and identified six Stage I cases with recurrence <5 years. The Ethics Committee of Peking Union Medical College Hospital specifically approved this study (No. S-K413), and all included patients provided written informed consent to participate in the study.

To the Editor: Congenital heart diseases (CHDs) are the most common congenital structural anomalies in China. Most of them are curable after birth. However, some defects progress during fetal period, thus resulting in high neonatal mortality and morbidity. Pulmonary atresia with intact ventricular septum (PA/IVS) during fetal period is partly associated with right ventricle (RV) hypoplasia and its consequent hemodynamic deterioration, which limits the possibility of biventricular (BV) repair after birth. The 1-year survival of PA/IVS live births is around 70%, but the rate of BV outcome is around 30%.^[1]

To the Editor: Achalasia is a primary esophageal motility disorder.^[1]The etiology of achalasia remains unknown, but it is associated with degeneration, reduction, or absence of neurons in the esophageal muscular layer (Auerbach’s plexus), leading to nerve–muscle conduction abnormalities.^[2]It has been demonstrated that excitatory neurons induce calcium ion (Ca²⁺) activity and contract smooth muscles by releasing acetylcholine^[3]in esophagus, and nitric oxide (NO) and vasoactive intestinal peptide (VIP) induce smooth muscle relaxation by inhibitory neurons.^[4]Hydrogen sulfide synthases may also be involved.^[5]We measured expression of L-type calcium channels (LTCCs),^[6]ryanodine receptors (RyRs),^[7]inositol 1,4,5-trisphosphate receptors (IP₃Rs),^[7]and NO synthases (NOSs)^[4,8]in circular muscles of the lower esophagus of achalasia patients. The result provides a better understanding for the pathogenesis of achalasia.