2020年 · 第133卷第19期

According to GLOBOCAN 2018, the global cancer statistic database by the International Agency for Research on Cancer, breast cancer is the most commonly diagnosed cancer in women.^[1]In 2018, more than 2 million new breast cancer cases were reported, with an age standardized rate (ASR) of 46.3 per 100,000, and over 600,000 deaths from breast cancer were estimated, with an ASR of 13.0 per 100,000, worldwide. The number of breast cancer cases continues to increase. In China, more than 270,000 new cases were diagnosed in 2015, with 70,000 reported deaths.^[2]In 2018, the number of new cases in the country increased to 367,900.^[1]Thus, we urgently need more clinical researches and expert consensus on optimal therapies for breast cancer.

The term non-alcoholic fatty liver disease (NAFLD) was coined in 1980 to characterize a disease similar to alcoholic fatty liver disease that developed in patients without a history of excessive alcohol intake.^[1]Morphologically, NAFLD is characterized by excess fatty infiltration of the liver in the absence of known causes of liver disease (eg, alcohol, autoimmune liver disease, viral hepatitis, etc). The clinical manifestations of NAFLD (both hepatic and extrahepatic) depend on the outcome of complex interactions between its primary drivers including poor lifestyle habits and diet, a dysfunctional microbiota, genetic predisposition, and environmental cues that result in metabolic dysfunction and liver disease. However, bringing all patients with their markedly different clinical courses under the NAFLD umbrella belies its complexity and implies a homogeneous disease state that then negatively impacts clinical management and a deeper understanding of pathogenesis. With advances in current knowledge on the spectrum of fatty liver diseases, it is apparent that the four-decade-old outdated term NAFLD can no longer serve to usefully describe a highly heterogeneous disease. The disease as we understand it today not only impacts patients who consume alcohol and those who do not, but also potentially impacts all patients with any form of liver disease, by acting as a disease modifier.^[2]

After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function.

A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function.

Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function.

A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.

The standard treatment for pediatric differentiated thyroid carcinoma (DTC) still requires consideration because of a lack of clinical evidence. The purpose of this study was to summarize the clinical experiences and explore the risk factors for post-operative recurrence through a retrospective analysis to develop better clinical strategies for pediatric DTC.

This study retrospectively analyzed children and adolescents with DTC who were treated between January 1999 and December 2014 at the Cancer Hospital, Chinese Academy of Medical Sciences. Clinicopathological results and outcomes were collected. A log-rank test of Kaplan-Meier curves and the Cox regression model were used to determine the factors associated with recurrence.

Data of 150 patients were collected in this study. During the follow-up, there was only one disease-related death. The recurrence rates at 3, 5, and 10 years were 13.6%, 18.7%, and 28.6%, respectively. There was a significant difference in the rate of recurrence according to age (P < 0.001), extrathyroidal extension (P < 0.001), lymph node metastasis (P = 0.023), and invasion of the trachea and esophageal wall (P = 0.004). Cox regression analysis demonstrated that age (P = 0.006) and extrathyroidal extension (P = 0.013) were significant dependent factors of post-operative recurrence.

The prognosis of DTC in children and adolescents is favorable. A close follow-up is recommended because of the high recurrence rate. A comparatively higher recurrence rate was observed in the younger age group, and new age-based divisions may be needed to conveniently evaluate the possibility of recurrence.

B-cell activating factor (BAFF) is vital for B cell survival. Serum BAFF levels are elevated in thrombotic antiphospholipid syndrome, but little is known about levels in patients with positive antiphospholipid antibodies (aPLs) and previous adverse pregnancy outcomes (APOs). We aimed to analyze serum BAFF concentrations of these patients in early pregnancy along with different pregnancy outcomes.

Thirty-six pregnant patients positive for aPLs and previous APOs (patient group), 25 healthy pregnant females (HP group) and 35 healthy non-pregnant females (HNP group) from the Peking University Third Hospital, between October 2018 and March 2019, were enrolled in this study. Serum of HNP and serum of patients as well as HP in the first gestational trimester were collected. Enzyme-linked immunosorbent assay kits were used to measure serum BAFF and interferon-alpha (IFN-α) concentrations. Cytometric bead array analysis was used to measure serum concentrations of cytokines. The patient group was further divided into APOs and non-APOs (NAPOs) group, fetal loss and live birth group according to pregnancy outcomes. The Mann-Whitney U-test was used to assess significance between and within groups. Spearman rank-order was used to evaluate correlation coefficients between BAFF and related cytokines.

The serum BAFF level in HP group was significantly lower than HNP group (245.24 [218.80, 265.90] vs. 326.94 [267.31, 414.80] pg/mL, Z = -3.966, P < 0.001). The BAFF level was obviously elevated in patient group compared to that in HP group (307.77 [219.86, 415.65] vs. 245.24 [218.80, 265.90] pg/mL, Z = -2.464, P = 0.013). BAFF levels in APOs group tended to be higher than that in NAPOs group (416.52 [307.07, 511.12] vs. 259.37 [203.59, 375.81] pg/mL, Z = -2.718, P = 0.006). Compared to HP group, concentrations of IFN-α, interleukin (IL-6) and tumor necrosis factor were higher in patient group (33.37 [18.85, 48.12] vs. 13.10 [6.85, 25.47] pg/mL, Z = -2.023, P = 0.043; 39.16 [4.41, 195.87] vs. 3.37 [2.92, 3.90] pg/mL, Z = -3.650, P < 0.001; 8.23 [2.27, 64.46] vs. 1.53 [1.25, 2.31] pg/mL, Z = -3.604, P < 0.001, respectively). Serum BAFF levels had a positive correlation with the concentrations of both IL-6 and IL-10 (IL-6: r = 0.525, P = 0.002; IL-10: r = 0.438, P = 0.012).

Serum BAFF levels are increased in patients with positive aPLs and previous APOs as compared to healthy pregnant females and tend to be higher in individuals with current APOs. The BAFF levels have a positive correlation with serum IL-6 and IL-10.

Coronary atherosclerotic plaque could go through rapid progression and induce adverse cardiac events. This study aimed to evaluate the impacts of smoking status on clinical outcomes of coronary non-target lesions.

Consecutive patients with coronary heart disease who underwent two serial coronary angiographies were included. All coronary non-target lesions were recorded at first coronary angiography and analyzed using quantitative coronary angiography at both procedures. Patients were grouped into non-smokers, quitters, and smokers according to their smoking status. Clinical outcomes including rapid lesion progression, lesion re-vascularization, and myocardial infarction were recorded at second coronary angiography. Multivariable Cox regression analysis was used to investigate the association between smoking status and clinical outcomes.

A total of 1255 patients and 1670 lesions were included. Smokers were younger and more likely to be male compared with non-smokers. Increase in percent diameter stenosis was significantly lower (2.7 [0.6, 7.1]% vs. 3.5 [0.9, 8.9]%) and 3.4 [1.1, 7.7]%, P= 0.020) in quitters than those in smokers and non-smokers. Quitters tended to have a decreased incidence of rapid lesions progression (15.8% [76/482] vs. 21.6% [74/342] and 20.6% [89/431], P= 0.062), lesion re-vascularization (13.1% [63/482] vs. 15.5% [53/432] and 15.5% [67/431], P= 0.448), lesion-related myocardial infarction (0.8% [4/482] vs. 2.6% [9/342] and 1.4% [6/431], P= 0.110) and all-cause myocardial infarction (1.9% [9/482] vs. 4.1% [14/342] and 2.3% [10/431], P= 0.128) compared with smokers and non-smokers. In multivariable analysis, smoking status was not an independent predictor for rapid lesion progression, lesion re-vascularization, and lesion-related myocardial infarction except that a higher risk of all-cause myocardial infarction was observed in smokers than non-smokers (hazards ratio: 3.00, 95% confidence interval: 1.04-8.62, P= 0.042).

Smoking cessation mitigates the increase in percent diameter stenosis of coronary non-target lesions, meanwhile, smokers are associated with increased risk for all-cause myocardial infarction compared with non-smokers.

Data on the evolution of recent small sub-cortical infarcts are limited, especially in the Chinese. Previous studies have reported a large heterogeneity in cavitation and infarct location; therefore, the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.

Patients who had experienced a recent, single, small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging (MRI) scan were retrospectively identified from January 2014 to June 2018. Time to follow-up imaging, baseline infarct size, vascular risk factors, and other clinical data, as well as the morphologic changes of the index infarct and surrounding white matter were recorded. Demographic, clinical and MRI characteristics were respectively compared among three groups (white matter hyper-intensitie [WMH] vs. cavitation vs. absent) and between with and without new WMH formation groups. In addition, logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.

Seventy-eight subjects were included with a median follow-up time of 304 days (range: 124-552 days). We found a significant reduction in infarct size at follow-up: 46 of 78 (59.0%) infarctions showed some degree of cavitation, 19 of 78 (24.4%) index lesions resembled non-cavitated WMH, and 13 of 78 (16.7%) infarcts had disappeared at follow-up MRI. No factors were found to be associated with differential outcomes of the infarcts. In addition, 8 of 78 (10.3%) patients demonstrated new WMH formation surrounding the index infarct; white matter progression (odds ratio = 15.95, 95% confidence interval = 1.65-153.99; P = 0.017) was an independent risk factor of new WMH formation.

More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities, demonstrating that these infarcts can be reduced and go undetected. The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases. Additionally, white matter progression is an independent risk factor, which may be a potential therapeutic target.

In recent years, visual quality has been extensively investigated in various conditions. In this community-based population study, we analyzed the effects of aging, refraction, and Lens Opacification Classification System III (LOCSIII) score on retinal imaging quality in healthy Chinese adults.

This cross-sectional study was conducted on sub-group subjects from The Handan Eye Study between October 2012 and January 2013. Healthy subjects over 30-years-old with logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) less than 0 were included. Retinal image quality was measured by optical quality analysis system (OQAS) and recorded as modulation transfer function cutoff frequency (MTF_cutoff), OQAS value (OV) 100%, OV20%, OV9%, Strehl ratio (SR), and objective scatter index (OSI). The correlation between age, spherical equivalent refraction (SE), LOCSIII score, and optical quality parameters were investigated by multivariate analysis.

Among 1108 verified subjects, 690 subjects (1380 eyes) met the inclusion criteria. Their age ranged from 30 to 76 years, SE ranged from -4.75 to 2.75 D. They were divided into five age groups (30-39, 40-49, 50-59, 60-69, and ≥70 years) for further analysis. After multivariate analysis by mixed-effect linear model, SR (t = -3.03, P = 0.002), OV20% (t = -2.39, P = 0.017), and OV9% (t = -3.16, P = 0.001) significantly decreased with the increasing age, whereas logMAR BCVA (t = 4.42, P < 0.001) and OSI (t = 4.46, P < 0.001) significantly increased with age. As SE increased, SR (t = 2.74, P = 0.01), OV20% (t = 2.31, P = 0.02), and OV9% (t = 2.79, P = 0.005) significantly elevated, and OSI (t = -3.38, P < 0.001) significantly decreased. With the increase in cortical opacity score, all optical quality parameters except for SR significantly decreased, including MTF_cutoff (t = -2.78, P = 0.01), OV100% (t = -2.78, P = 0.005), OV20% (t = -2.60, P = 0.009), and OV9% (t = -2.05, P = 0.04). As posterior sub capsular opacity score increased, MTF_cutoff (t = -2.40, P = 0.02) and OV100% (t = -2.40, P = 0.01) significantly decreased, while OSI (t = 7.56, P < 0.001) significantly increased.

In healthy Chinese adult population, optical quality-related parameters significantly decrease with the increasing age, and OSI significantly increases with age. In normal BCVA subjects, optical quality is significantly impacted by cortical and posterior sub capsular opacity rather than by nuclear opacity.

Interleukin-18 (IL18) gene polymorphisms are related to many inflammatory and autoimmune diseases. However, a correlation analysis between IL18-607C/A and -137G/C gene polymorphisms and Takayasu arteritis (TA) is lacking.

This study enrolled 200 patients with TA as the case group and 334 region-, age-, and sex-matched healthy subjects as the control group. We genotyped alleles and genotypes at positions -607 and -137 of the IL18 gene and analyzed the distribution frequencies. Mann-Whitney U test, t test, Chi-squared test and Hardy-Weinberg equilibrium were performed.

After adjusting for risk factors, the adjusted odds ratios and 95% confidence intervals at position -607C/A were 0.533, 0.391 to 0.880 (P = 0.010); 0.266, 0.586 to 1.002 (P = 0.051); and 0.122, 0.552 to 1.420 (P = 0.613) under the dominant, additive, and recessive models, respectively. For the -137G/C polymorphism, the adjusted odds ratios and 95% confidence intervals were 1.571, 1.068 to 2.311 (P = 0.022); 1.467, 1.086 to 1.980 (P = 0.012); and 1.815, 0.901 to 3.656 (P = 0.095) under the dominant, additive, and recessive models, respectively. Moreover, regardless of the model used, we found no statistical difference in distribution frequency between the active and quiescent states of TA for the -607C/A (P = 0.355, 0.631, and 0.705, respectively) and -137G/C polymorphisms (P = 0.205, 0.385, and 0.208, respectively).

The IL18-607C/A gene polymorphism may decrease the risk of TA, and thus is a protective factor, whereas -137G/C may increase the risk of TA, and thus is a risk factor. However, neither polymorphism was related to activity (active vs. quiescent) of TA.

Topoisomerase II alpha (TOP2A) has been reported to play a crucial role in the tumorigenesis of various cancer types. However, the biological role of TOP2A in gallbladder cancer (GBC) remains unknown. The current study aimed to explore the function and potential mechanism of TOP2A in GBC.

Based on Gene Expression Profiling Interactive Analysis data, we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues. In vitro, cell proliferation, migration, and invasion ability were examined by cell counting kit-8 and transwell assay, respectively. Epithelial-mesenchymal transition (EMT) related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related markers were measured by Western blotting. Xenograft model assay was performed to evaluate the effect of TOP2A in vivo.

TOP2A was found up-regulated in GBC (tumor vs. normal, 12.62 vs. 0.34) and correlated with the late tumor node metastasis stage (P = 0.0032), present of lymph node metastasis (P = 0.0273), and poor prognosis in GBC patients (log-rank P = 0.028). In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation, migration, invasion, EMT process, and tumor growth in GBC. In addition, TOP2A down-regulation significantly decreased the protein levels of phosphor (p)-PI3K, p-Akt, and p-mTOR.

Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients. TOP2A promotes GBC cell proliferation, migration, invasion, EMT process, and tumor growth through activating PI3K/Akt/mTOR signaling pathway, and may serve as a novel prognostic biomarker and therapeutic target for GBC.

The methods of fecal microbiota transplantation (FMT) and the related results vary a lot among centers worldwide. Therefore, methodologic standardization can improve the clinical practice and trials about FMT. A panel of 28 experts from 22 hospitals or institutes in 15 cities has contributed to the present consensus on washed microbiota transplantation (WMT).^[1]This consensus provides guidance on the methodology of WMT, which is different from that of the manually FMT in recent experts’ consensus or recommendations.^[2,3]All experts were assigned, according to their expertise, to the following five groups: Group 1, donor screening; Group 2, washing microbiota protocol, storing, and transport; Group 3, patient preparation; Group 4, delivery decision; Group 5, safety and management. Each statement and the following comment have passed a Delphi process and a face-to-face plenary meeting. The best available evidence was assessed according to the Grading of Recommendations Assessment, Development and Evaluation system.

For the past decades, the rapid growth of economy and transition of lifestyles have led to a rapid rise in the prevalence of diabetes in China. Due to the lack of standard process in prevention and management of diabetic kidney disease (DKD) in China, the Peking University Health Science Center organized experts in fields of nephrology and endocrinology to develop the Chinese consensus statement of DKD. This consensus emphasizes on evidence-based inquiry, and focuses on the following three topics: (1) risk factors of the incidence and progression of DKD; (2) the diagnosis of DKD and indication of renal biopsy; (3) the overall management of DKD.

Syphilis, caused byTreponema pallidumsubsppallidum(T. pallidum), is a chronic, systemic human disease transmitted through sexual contact. The incidence and prevalence of syphilis is still high in China.^[1]To guide the prevention measures and management of this disease, we renew the guidelines on diagnosis and treatment of syphilis [Supplementary file, http://links.lww.com/CM9/A292]. Manifestations and diagnosis of all stages of syphilis are presented inTable 1, and management inTable 2.

Brain metastasis (BM) of lung cancer is not rare in the course of tumor development. The overall survival (OS) of patients diagnosed with BM is only 3.6 months without radiotherapy. With rapid developments in treatment for BM, a median survival time (MST) of approximately 16 months could be achieved.^[1]For patients with epidermal growth factor receptor mutations or anaplastic lymphoma kinase gene rearrangements, corresponding agents have been approved for treatment. In patients without driven genes mutation, radiation therapy remains the standard regimen for BM.

Portal hypertension (PHT) is the trigger of the severe complications of cirrhosis, including esophagogastric variceal bleeding (EVB), ascites, hepatic encephalopathy, cirrhotic cardiomyopathy, acute kidney injury and hepatorenal syndrome (AKI-HRS), which may cause death or increase the need for liver transplantation.^[1,2]Of these, EVB remains one of the deadliest complications of PHT. As of now, the most widely accepted measure to assess portal pressure (PP) and PHT is the hepatic venous pressure gradient (HVPG) via transjugular-hepatic vein balloon catheterization.^[3]The pharmacological management of PHT aims to reduce PP and prevent PHT-related complications.^[4,5]Given that PP is determined by portal blood flow and hepatic vascular resistance,^[4]currently used drugs are mainly targeted to modulate the increased liver blood flow, such as reducing hyperdynamic circulation, renin-angiotensin-aldosterone system activation, vascular hyperplasia, and collateral circulation formation, or decrease intravascular resistance, such as inhibiting liver fibrosis, regenerative nodules, and angiogenesis.^[6]In the setting of PHT, arterial vasodilation occurs both in the splanchnic and systemic circulation, therefore, activates the neurohumoral and vasoconstrictive systems, which leads to sodium and water retention, increased blood volume, and increased cardiac output.^[7]Terlipressin, somatostatin (SMT) or octreotide, and non-selective β-blockers (NSBBs) decrease the portal venous inflow through splanchnic vasoconstriction. However, the crosstalk between vasoactive substances and contractile cells often leads to abnormal liver microcirculation and PHT development.^[6]Those may be new targets for the pharmacological management of PHT in the future.

Brain injury, such as traumatic brain injury and stroke, are important causes of death and long-term disability all over the world.^[1]Inflammation may play an essential role in secondary injury after brain injury. Neural stem cells (NSCs) are pluripotent cells with self-renewal ability. It is initially assumed that NSCs transplantation promotes tissue restoration by direct structural cell replacement. However, the view has been recalibrated over the past decade. Bystander effect providing immunomodulatory, neurotrophic, and reparative support may play a major role instead.^[2]However, the specific action mode of NSCs to exert immunomodulatory effect is still a lack of knowledge. On the one hand, the secretion of CD200, CX3 chemokine ligand 1 (CX3CL1), NSC-derived exosomes (NSC-Exos), and the regulation of nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) can inhibit the inflammatory effects of microglia. On the other hand, changes in the systemic immune response also function in the immunomodulatory process. This article will focus on these aspects to discuss the potential immunoregulation mechanisms of NSCs.

Although some researchers hypothesized that neoadjuvant chemotherapy may improve prognosis of patients with breast cancer because it allows them to receive earlier systemic treatment, no large randomized controlled trials have confirmed this hypothesis. Thus, it is generally accepted that there is no difference in disease-free survival (DFS) or overall survival (OS) for patients receiving neoadjuvant or adjuvant chemotherapy for breast cancer.^[1,2]Karagianniset al^[3]published an article in 2017 that incited some controversy because it reported that neoadjuvant chemotherapy promoted breast cancer micrometastasis to the blood vessels and lungs, based on the study of a polyomavirus middle T antigen mouse model and human xenograftin vivoand in fixed tissue.

Scleroderma is an autoimmune fibrosing disorder that can be further subclassified as localized scleroderma (LSc) and systemic sclerosis (SSc). LSc is characterized by sclerotic and pigmented skin lesions, while SSc is a more generalized disorder of the connective tissue involving a number of organs. SSc is characterized by the thickening of dermal collagen bundles, fibrosis, and vascular abnormalities in the visceral organs.^[1]Despite the differences in their morphologic features and clinical presentation, these two diseases do share some characteristics including endothelial cell dysfunction, T helper 2 (Th2) cell dominance during immune activation and excess fibrosis of the skin with similar pathologic findings, leading to the hypothesis that SSc and LSc share an underlying mechanism of pathogensis. Currently, multiple lines of evidence suggest that genetic factors may contribute to SSc susceptibility.^[2]Human leukocyte antigen (HLA) genes are closely linked to SSc susceptibility, with studies describing some correlation between SSc andHLA-B,HLA-C,HLA-DRA,HLA-DRB1,HLA-DRB5,HLA-DQA1,HLA-DQB1,HLA-DMB,HLA-DOA,HLA-DPA1,HLA-DPB1, andHLA-DPB2.^[2]A large number of non-HLAgenes have also been reported to be associated with the development of SSc, these include connective tissue growth factor gene (TGF), signal transducer and activator of transcription gene (STAT4) amongst others [Supplementary Table 1, http://links.lww.com/CM9/A294]. However, only some of these results could be verified in additional studies and similar studies in the Chinese population remain extremely limited. Interestingly, genes like interleukin 1 (IL-1), ras homolog family member B (RHOB), family with sequence similarity 167-member A-BLK proto-oncogene (FAM167A-BLK),STAT4, interferon regulatory factor 5 gene (IRF5),HLA-DPB1, and keratin1 (KRT1) have all been linked to SSc susceptibility in the Chinese population.^[3]Although it has been reported that LSc tends to exhibit some form of familial inheritance, there have been no clearly identified heritable traits for this disease. Additionally, no study, to our knowledge, has investigated the common genetic factors for LSc and SSc. Thus, it would be of significant interest to examine the susceptibility of LSc and determine whether there are any correlations between the genetic profiles of SSc and LSc. This study aimed to identify the genetic profile of LSc patients and any shared genetic features of SSc and LSc in the Chinese population. Furthermore, this study evaluated the occurance of previously described SSc loci in the Chinese population and compared their frequency with those reported in other ethnic communities.

Despite major advances achieved in percutaneous coronary intervention (PCI) and antithrombotic therapies, in-stent restenosis (ISR) is still a challenging clinical problem after PCI. It is very important to identify a new parameter for ISR risk stratification and as potential pharmacological targets. We previously reviewed that Neutrophil-to-lymphocyte ratio (NLR) may be the best predictor of ISR among several parameters of blood cells. Type 2 diabetes mellitus (T2DM) is closely related to inflammation and acts as an independent risk factor of ISR. However, few studies have evaluated the predictive role of the dynamic changes of NLR on ISR in patients with T2DM. Therefore, we aimed to analyze preprocedural NLR value in the first PCI and the second coronary angiography (CAG), and evaluate its predictive value on ISR in patients with T2DM.

48% to 69% of patients experience moderate to severe pain during the 48 h after craniotomy.^[1]Uncontrolled pain potentiates sympathetic activation, which may elevate arterial and intracranial pressure and result in intracranial haemorrhage. Currently, opiates are commonly used for post-operative analgesia. However, the promising analgesic effects of opiates come at the price of increased incidences of post-operative nausea and vomiting. Non-steroidal anti-inflammatory drugs are not commonly administered mainly because of concern for intracranial bleeding. Pre-operative incisional infiltration and scalp nerve blockage are clinically performed strategies^[2]; however, limited evidence is available to support the superiority of the therapeutic benefits of either strategy. Currently, there is a lack of effective, safe, simple and non-invasive approaches for the treatment or prevention of post-craniotomy pain.

Exosomes are a class of membranous vesicles, which are approximately 50 to 100 nm in diameter; they are released into the extracellular matrix from various cells.^[1]Exosomes are rich in proteins, lipids, and nucleic acids. They have been reported to be involved in various physiological processes and are important tools for intercellular material and information communication.^[2,3]Increasing evidence has indicated that exosomes can be extracted from human saliva, urine, blood, and other body fluids.^[4]However, whether exosomes exist in nipple discharge remains unknown. In this study, exosomes from nipple discharge of breast cancer patients and colostrum of postpartum women were isolated using ultracentrifugation. The exosomes were identified by transmission electron microscopy (TEM), Western blot, and nanoparticle tracking analysis (NTA). The detailed methods are shown in Supplementary File 1, http://links.lww.com/CM9/A286. The study was approved by the Ethics Committee of Qilu Hospital of Shandong University (No. KYLL-2018-096), and all patients provided written informed consent.

To the Editor:Persistent trigeminal artery (PTA) is one of the most common remaining fetal anastomoses. During embroyotic development, the link between the carotid and vertebral basilar circulation would normally regress. Carotid artery dissection (CAD) is a common cause of cerebral ischemia in young people, which can be caused by hyperhomocysteinemia (HHcy) possibly due to gene mutation. We report a case of posterior circulation ischemia caused by CAD.

To the Editor:Acne inversa (AI), also known as hidradenitis suppurativa, is a chronic recurrent inflammatory skin disease characterized by deep painful nodules and abscesses with resultant scarring mainly distributed in intertriginous areas. Loss-of-function mutations in γ-secretase (GS) genes are responsible for familial AI.^[1]GS is a transmembrane protease composed of four essential protein subunits: one catalytic presenilin subunit (PSEN) and three cofactor subunits (nicastrin [NCSTN], presenilin enhancer 2 [PSENEN], anterior pharynx defective 1). GS is involved in cleavage of various type I membrane proteins, including amyloid precursor protein and Notch proteins. PSENEN directly binds to PSEN and is required for its autocatalytic cleavage and protease activity. To date, six mutations have been reported inPSENEN, all of which result in frameshift truncations and altered protein products, predominantly leading to haploinsufficiency.^[2]Psoriasis is a genetically-determined proliferative and inflammatory entity, resulting from complex interactions between aberrant keratinocyte proliferation and differentiation, and a T-lymphocytemediated immune process. Dowling-Degos disease (DDD), a rare autosomal dominant disorder, is characterized by progressive reticulate hyperpigmentation and small darkbrown hyperkeratotic papules, mainly affecting flexural areas.^[3]Herein, we report a proband and three other members of a three-generation Chinese Han AI family with co-occurrence of psoriasis and DDD, respectively.

To the Editor:Collision tumors are rare neoplasms comprising two cell populations that develop in juxtaposition to one another with minimal to no areas of intermingling.^[1]The most common sites at which collision tumors occur have been reported to include the lungs, cranium, rectum, liver, uterus, bladder, and testis.^[2,3]However, the biologic behavior of esophageal collision tumors remains largely unknown, with only a small number of studies originating from case reports having been published. This study reports five cases of esophageal collision tumors to provide evidence-based recommendations for the care of future patients.

To the Editor: Pulmonary artery stenosis can be caused by numerous factors, such as tetralogy of Fallot, pulmonary atresia, tricuspid atresia with pulmonary artery stenosis, atresia combined with another congenital heart disease and pulmonary circulation dysplasia,^[1,2]William syndrome, and Alagille syndrome. Additionally, pulmonary artery branch stenosis can be the consequence of some genetic metabolic diseases, such as congenital rubella.^[3]Most cases of pulmonary stenosis require surgical intervention.

To the Editor:A 25-year-old Chinese man complained of a swelling nodule over his right neck for 3 months, without pain, pruritus, or dermatitis. The patient had suffered from Budd-Chiari syndrome (BCS) since 2016, which was well controlled after receiving interventional treatment (angioplasty with stenting) in 2017 and appropriate management later. The patient had no history of hypertension or diabetes. The patient exhibited an oval-shaped subcutaneous swelling over his right neck region. Physical examination found that the border of the mass was clearly distinguished, without adhesions to the adjacent tissue, and measured 2.5 cm in diameter. Blood pressure and heart rate were 128/84 mmHg and 76 beats/min, respectively.