2019年 · 第132卷第24期

Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.

We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.

A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ² = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7% vs. 10.7%, χ² = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ² = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development(hazard ratio 18.017, 95% confidence interval: 5.803–55.938; P < 0.001).

As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.

Despite the growing epidemic of heart failure (HF), there is limited data available to systematically compare noncardiac comorbidities in the young-old, old-old, and oldest-old patients hospitalized for HF. The precise differences will add valuable information for better management of HF in elderly patients.

A total of 1053 patients aged 65 years or older hospitalized with HF were included in this study. Patients were compared among three age groups: (1) young-old: 65 to 74 years, (2) old-old: 75 to 84 years, and (3) oldest-old: ≥85 years. Clinical details of presentation, comorbidities, and prescribed medications were recorded.

The mean age was 76.7 years and 12.7% were 85 years or older. Most elderly patients with HF (97.5%) had at least one of the non-cardiac comorbidities. The patterns of common non-cardiac comorbidities were different between the young-old and oldestold group. The three most common non-cardiac comorbidities were anemia (53.6%), hyperlipidemia (45.9%), and diabetes(42.4%) in the young-old group, while anemia (73.1%), infection (58.2%), and chronic kidney disease (44.0%) in the oldest-old group. Polypharmacy was observed in 93.0% elderly patients with HF. Additionally, 29.2% patients were diagnosed with infection, and 67.0% patients were prescribed antibiotics. However, 60.4% patients were diagnosed with anemia with only 8.9% of them receiving iron repletion.

Non-cardiac comorbidities are nearly universal in three groups but obviously differ by age, and inappropriate medications are very common in elderly patients with HF. Further treatment strategies should be focused on providing optimal medications for age-specific non-cardiac conditions.

The results of the Trial Assigning IndividuaLized Options for Treatment (TAILORx) suggested that approximately 70% of T1-2N0M0, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients can avoid chemotherapy and receive only adjuvant endocrine therapy. We conducted a retrospective analysis of the clinicopathologic features and prognostic factors of patients with breast cancer who met the inclusion criteria of the TAILORx trial.

According to the enrollment criteria of the TAILORx trial, a retrospective analysis was performed on patients with breast cancer who were treated from January 2008 to December 2015 at Peking University First Hospital. The clinicopathologic characteristics of all patients were analyzed, and prognoses were calculated using the Kaplan-Meier method and a Cox proportionate hazards model.

A total of 2430 patients with early stage breast cancer who were admitted at our hospital had complete clinicopathologic data and follow-up information. Of these patients, 722 met the inclusion criteria and were enrolled in the present study, accounting for 29.7% of all patients. Among them, 417 (57.8%) patients received only adjuvant endocrine therapy (the non-chemo group), and 305 (42.2%) patients received adjuvant chemotherapy followed by adjuvant endocrine therapy (the chemo group). No statistically significant difference was observed in overall survival (OS) between the two groups (non-chemo vs. chemo: 5-year OS: 97.9% vs. 97.9%, χ² = 1.00, P = 0.995; hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.46–2.21). A significant difference was observed in disease-free survival (DFS) between the two groups (non-chemo vs. chemo: 5-year DFS: 97.9% vs. 94.7%, χ² = 8.65, P = 0.003; HR = 3.05, 95% CI: 1.40–6.67). The choice of adjuvant therapy was associated with clinicopathologic factors, such as the age at diagnosis, T stage, histologic grade, the Ki67 index, the presence of intravascular tumor thrombus (P < 0.001), pathologic type, and menstrual status (P = 0.014).

In the absence of internationally recognized multigene testing methods, for patients with early hormone receptorpositive, HER2-negative breast cancer, clinicians can develop a treatment plan based on clinicopathologic features only, which can effectively screen some patients who do not need adjuvant chemotherapy. However, nearly half of patients still receive adjuvant chemotherapy, and whether these patients can be exempted from chemotherapy warrants further exploration.

Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lowergrade gliomas that carry IDH2 mutations.

Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O⁶-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test.

Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively).

IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation.

Leukocyte telomere has been shown to be related to insulin resistance-related diseases, such as type 2 diabetes mellitus(T2DM) and non-alcoholic fatty liver disease (NAFLD). This cross-sectional study investigated the association of leukocyte telomere length (LTL) with NAFLD in T2DM patients.

Clinical features were collected and LTL was measured by Southern blot-based terminal restriction fragment length analysis in 120 T2DM patients without NAFLD and 120 age-matched T2DM patients with NAFLD. NAFLD was clinically defined by manifestations of ultrasonography. The correlation between LTL and clinical and biochemical parameters were analyzed by Pearson correlation or Spearman correlation analysis. Factors for NAFLD in T2DM patients were identified using multiple logistic regressions.

LTL in T2DM patients with NAFLD were significantly longer than those without NAFLD (6400.2 ± 71.8 base pairs [bp] vs. 6023.7 ± 49.5 bp, P < 0.001), especially when diabetes duration was less than 2 years. Meanwhile, the trend of shorter LTL was associated with the increased diabetes duration in T2DM patient with NAFLD, but not in T2DM patients without NAFLD. Finally, LTL (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000–1.002, P = 0.001), as well as body mass index (OR: 1.314, 95% CI: 1.169–1.477, P < 0.001) and triglycerides (OR: 1.984, 95% CI: 1.432–2.747, P < 0.001), had a significant association with NAFLD status in T2DM patients.

T2DM patients with NAFLD had a significantly longer LTL than those without NAFLD. The longer LTL was especially evident in the early stage of T2DM, indicating that longer LTL may be used as a biomarker for NAFLD in T2DM patients.

The pathogenesis of multiple sclerosis (MS) is mediated primarily by T cells, but most studies of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have focused on CD4⁺ T cells. The aims of the current study were to determine the pathological interrelationship between CD4 and CD8 autoreactive T cells in MS/EAE.

Female C57BL/6 mice (n =20) were induced by myelin oligodendrocyte glycoprotein (MOG) _35-55 peptide. At 14 days after immunization, T cells were isolated from the spleen and purified as CD4⁺ and CD8 ⁺ T cells by using CD4 and CD8 isolation kits, and then the purity was determined by flow cytometric analysis. These cells were stimulated by MOG_35–55 peptide and applied to proliferation assays. The interferon-gamma (IFN-γ) and interleukin (IL)-4 secretion of supernatant of cultured CD4 ⁺ and CD8 ⁺ T cells were measured by enzyme-linked immunosorbent assays (ELISA). For adoptive transfer, recipient mice were injected with MOG_35–55-specific CD8⁺ or CD4⁺ T cells. EAE clinical course was measured by EAE score at 0–5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining.

CD8⁺CD3⁺ and CD4⁺CD3 ⁺ cells were 86% and 94% pure of total CD3⁺ cells after CD8/CD4 bead enrichment, respectively. These cells were stimulated by MOG_35–55 peptide and applied to proliferation assays. Although the CD8⁺ T cells had a generally lower response to MOG_35–55 than CD4⁺ T cells, the response of CD8⁺ T cells was not always dependent on CD4. CD8⁺ T cell secreted less IFN-γ and IL-4 compared with CD4⁺ T cells. EAE was induced in wildtype B6 naïve mice by adoptive transfer of MOG_35–55-specific T cells from B6 active-induced EAE (aEAE) mice. A similar EAE score and slight inflammation and demyelination were found in naive B6 mice after transferring of CD8 ⁺ T cells from immunized B6 mice compared with transfer of CD4 ⁺ T cells.

Our data suggest that CD8⁺ autoreactive T cells in EAE have a lower encephalitogenic function but are unique and independent on pathogenic of EAE rather than their CD4⁺ counterparts.

X-linked inhibitor of apoptosis (XIAP) is a vital factor in the anti-apoptosis mechanism of tumors and is highly expressed in renal cell carcinoma (RCC). However, the mechanism through which XIAP regulates DNA damage repair is unknown. This study investigated the regulatory mechanism of XIAP in etoposide-induced apoptosis in two Caki-1 cell lines with high or low XIAP expression.

The two cell lines were established using RNA interference technology. The differentially expressed proteins in the two cell lines were globally analyzed through an isobaric tags for relative and absolute quantitation-based quantitative proteomics approach. Proteomic analysis revealed 255, 375, 362, and 5 differentially expressed proteins after 0, 0.5, 3, and 12 h of drug stimulation, respectively, between the two cell lines. The identified differentially expressed proteins were involved in numerous biological processes. In addition, the expression of histone proteins (H1.4, H2AX, H3.1, H3.2, and H3.3) was drastically altered, and the effects of XIAP silencing were accompanied by the marked downregulation of H2AX. Protein-protein interactions were assessed and confirmed through immunofluorescence and Western blot analyses.

The results suggested that XIAP may act as a vital cell signal regulator that regulates the expression of DNA repair-related proteins, such as H2AX, and influences the DNA repair process.

Given these functions, XIAP may be the decisive factor in determining the sensitivity of RCC cell apoptosis induction in response to chemotherapeutic agents.

Tuberculosis (TB) is one of the most debilitating diseases worldwide. Current studies have shown that vitamin D plays a significant role in host immune defense against Mycobacterium tuberculosis, but clinical trials reported inconsistent results. Therefore, we systematically reviewed the literature to investigate whether vitamin D supplementation could improve the effect of anti-TB therapy.

We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from their inception to February 8th, 2019 for randomized controlled trials on vitamin D supplementation in patients with pulmonary TB receiving anti-TB therapy. The primary outcomes were time to sputum culture and smear conversion and proportion of participants with negative sputum culture. The secondary outcomes were clinical response to treatment and adverse events. A random-effects model was used to pool studies. Data were analyzed using RevMan 5.3 software.

Five studies with a total of 1126 participants were included in our meta-analysis. Vitamin D supplementation did not shorten the time to sputum culture and smear conversion (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.89–1.23, P = 0.60; HR 1.15, 95% CI 0.93–1.41, P = 0.20, respectively) and did not lead to an increase in the proportion of participants with negative sputum culture (relative risk [RR] 1.04, 95% CI 0.97–1.11, P = 0.32). However, it reduced the time to sputum culture conversion in the sub-group of participants with TaqI tt genotype (HR 8.09, 95% CI 1.39–47.09, P = 0.02) and improved the multidrug-resistant(MDR) TB sputum culture conversion rate (RR 2.40, 95% CI 1.11–5.18, P = 0.03). There was no influence on secondary outcomes.

Vitamin D supplementation had no beneficial effect on anti-TB treatment, but it reduced the time to sputum culture conversion in participants with tt genotype of the TaqI vitamin D receptor gene polymorphism and improved the MDR TB sputum culture conversion rate.

The clinical outcome of transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the femoral head (ONFH) remains controversial, and the promising clinical results of several Japanese studies could not be reproduced in American and European studies. Trying to solve controversies on TRO for ONFH rising from apparently conflicting studies, a meta-analysis was conducted to assess the 5- and 10-year hip survival rates (with conversion to artificial joint replacement and radiographic failure as endpoints) after TRO.

All eligible studies were searched in seven comprehensive databases including PubMed, Web of Science, Embase, Cochrane Library, VIP Database, China Knowledge Resource Integrated Database, and Wan Fang Database prior to June 2019. The outcomes evaluated were 5- and 10-year hip survival rates after TRO. The odds ratio and risk difference for the noncomparative binary data with the 95% confidence intervals (CIs) were calculated for each outcome. The included studies were assessed for methodologic bias and potential reasons for heterogeneity were explored.

Nineteen studies of TRO for ONFH were eligible for this meta-analysis according to inclusion criteria. Based on the previous report, two calculation methods (Methods 1 and 2) were adopted in this meta-analysis. Furthermore, we performed a subgroup analysis of the 5- and 10-year hip survival rates (Method 1) after TRO for ONFH: Asian sub-population and non-Asian subpopulation. Taking conversion to artificial joint replacement as the endpoint, 5- and 10-year hip survival rates (Method 1) after TRO for ONFH in the Asian population were 0.86 (95% CI = 0.82–0.89) and 0.72 (95% CI = 0.65–0.78), respectively, and 5- and 10- year hip survival rates after TRO for ONFH in the non-Asian population were 0.55 (95% CI= 0.43–0.67) and 0.42 (95% CI = 0.28–0.55), respectively. The 5- and 10-year hip survival rates (Method 2) after TRO for ONFH were 0.90 (95% CI = 0.79–0.95) and 0.89 (95% CI = 0.81–0.94), respectively. Taking radiographic failure as the endpoint, 5- and 10-year hip survival rates after TRO for ONFH were 0.70 (95% CI= 0.64–0.76) and 0.53 (95% CI= 0.46–0.61), respectively.

The 5- and 10-year hip survival rates after TRO for ONFH were satisfactory in the Asian population, and were acceptable in the non-Asian population despite high early failure rates.

To review the latest progress on the pathogenic mechanism and management of rheumatoid arthritis (RA)-associated coronary artery disease (CAD), and propose advice on future management optimization as well as prospects for research and development of new therapeutic regimen.

This study was based on data obtained from PubMed up to May 2019 using various search terms and their combinations, including coronary artery disease, myocardial ischemia, cardiovascular diseases, RA, rheumatic diseases, treatment, therapy, strategies, immunotherapy, inflammation, and anti-inflammation.

All retrieved literature was scrutinized, most relevant articles about the pathogenic mechanism and clinical management, especially anti-inflammatory therapy of RA-associated CAD were reviewed.

RA is an immune-mediated chronic inflammatory disease which has a great social disease burden. In addition to typical arthritic manifestations, RA also affects extra-articular tissues and organs, within which the involvement of the cardiovascular system, especially incorporating CAD, is the leading cause of death for patients with RA. Recently, numerous basic and clinical studies have been carried out on the mechanism of CAD development and progression under the inflammatory cascade of RA. The effect of traditional RA drugs on CAD risk management has been gradually clarified, and more emerging biologic agents are being explored and studied, which have also achieved satisfactory outcomes. Furthermore, with the success of the CANTOS clinical trial, novel anti-inflammatory therapy for the prevention of cardiovascular disease is believed to have a broad prospect.

RA is an independent risk factor for CAD, which mainly results from the underlying inflammatory cascade; therefore, anti-inflammatory therapy, especially the emerging novel biologic drugs, is important for CAD management in patients with RA and may also be a promising approach among the general population.

Endometriosis is a common gynecologic disease that frequently leading to chronic pelvic pain, severe dysmenorrhea, and subfertility. As first-line hormonal treatment can interfere with ovulation and may cause recurrent pelvic pain, exploration of new non-hormonal therapeutic approaches becomes increasingly necessary. This review aimed to evaluate the pre-clinical and clinical efficacy and safety of non-hormonal treatment for endometriosis

Databases including PubMed, Embase, Cochrane Library, SINOMED, ClinicalTrials.gov, and Google Scholar were searched up to October 2019, using search terms "endometriosis" and "non-hormonal therapy."

Twenty-four articles were reviewed for analysis, including nine animal studies and 15 human trials; all were published in English.

Twenty-four articles were identified, including 15 human trials with 861 patients and nine animal studies. Some agents have been evaluated clinically with significant efficacy in endometriosis-related pelvic pain and subfertility, such as rofecoxib, etanercept, pentoxifylline, N-palmitoylethanolamine, resveratrol, everolimus, cabergoline (Cb2), and simvastatin. Other drugs with similar pharmacological properties, like parecoxib, celecoxib, endostatin, rapamycin, quinagolide, and atorvastatin, have only been tested in animal studies.

Clinical data about most of the non-hormonal agents are not sufficient to support them as options for replacement therapy for endometriosis. In spite of this, a few drugs like pentoxifylline showed strong potential for real clinical application.

Resection of malignant pelvic bone tumors poses a major technique challenge for orthopedic oncologists due to the large tumor size which is undetectable at the early-onset and local complex anatomy with the severe extension to major neurovascular structures and intestinal and urinary tracts.^[1]Traditionally, malignant pelvic bone tumors were resected by the hindquarter amputation and the procedure obviously influenced the detrimental cosmetic and physical outcomes. More attempts have been made to perform the limb-salvage and improve the reconstruction of the pelvis after tumor resection. However, the abundant clinical experience could not be accumulated at the single tumor center due to the low incidence of pelvic bone tumors. Furthermore, the poor prognosis previously occurred to patients with tumors due to the anatomic complexity and scanty clinical experience. With the development of surgical skills and related discipline, many hospitals, especially Musculoskeletal Tumor Center of Peking University People’s Hospital (PKUPH), gathered a great deal of surgical experience of resecting the malignant pelvic tumors in the past two decades in China. The overall survival and limb-salvage rates and lower extremity function were significantly improved by more effects of many orthopedic oncologists in China in the past years. The present article was to review the limb-salvage surgery for the malignant pelvic tumors in the past two decades.

Ankle arthritis is a disease characterized by degeneration of articular cartilage, which is always accompanied with pain, decreased mobility, and varus deformity.

To the Editor:Cronkhite-Canada syndrome (CCS) is a rare, non-hereditary disease characterized by diffuse gastrointestinal polyposis and ectodermal abnormalities.^[1]Although CCS polyps are not considered to be neoplastic, 15% to 25% patients have been documented with colorectal or gastric cancer at diagnosis, and up to 40% of patients have been documented with adenomas and adenomatous changes.^[2]Extra-gastrointestinal neoplasms have been sporadically reported, but their association with CCS remains under investigation. The underlying mechanism of CCS has been less investigated, with only one whole exome sequencing (WES) study that identified a protein kinase DNA-activated catalytic subunit (PRKDC) DNA variant that might contribute to the pathogenesis.^[3]Here, we report a case of CCS that was complicated with three malignant tumors. WES analysis of this case identified certain germline mutations that might provide insight into the pathogenesis. This study was approved by the Ethics Committee of Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences (No. ZS-1725).

To the Editor:Spindle cell carcinoma (SpCC) is a rare histological type of sarcomatoid carcinoma consisting of spindle-shaped tumor cells. SpCC can occur in many different organs, including the lungs. There is limited data on the clinical presentation, genetic mutant phenotype, treatment, and outcome of lung SpCC. The efficacy of molecular targeted therapy for this tumor is still unclear.^[1]Here, we report an adult male with metastatic SpCC harboring a Tropomyosin 3-ROS proto-oncogene 1 (TPM3-ROS1)fusion who showed a long-term response to targeted therapy by crizotinib, a tyrosine kinase inhibitor (TKI).

To the Editor:A 25-year-old male patient was admitted to the First Affiliated Hospital, School of Medicine, Zhejiang University with complaints of fever, cough, and knee pain. He was an overseas student and had been back from the USA for 3 weeks, with no remarkable medical history before admission. He was initially diagnosed with a cold and given non-steroidal anti-inflammatory analgesics and oral antibiotics in a clinic. However, his symptoms were not alleviated. Swelling and pain in his left knee became worse so that normal walking was not possible. Gradually a red rash with mild pain above the epidermis appeared in the lower limbs. Then, the patient presented to a municipal hospital in Hangzhou, China, and underwent a chest computed tomography (CT) scan, which revealed highdensity areas in both the left lower lobe [Figure 1A] and left hilum [Figure 1B]. Laboratory tests indicated the following results: white blood cell (WBC) count 11.6 × 10⁹/L, neutrophils 88.2%, and C-reaction protein (CRP) 70.3 mg/dL. Community-acquired pneumonia was considered first, and empirical anti-bacterial treatment(moxifloxacin injection, 400 mg per day) was administered. The patient did not improve despite the use of moxifloxacin injections for 1 week but did have an elevation in liver enzymes (alanine transaminase [ALT] 191 U/L and aspartic transaminase [AST] 121 U/L), higher WBC count (16.6 × 10⁹/L) and higher CRP (213 mg/dL). His left knee joint swelling progressed, and the pain worsened. A magnetic resonance imaging scan of his left knee revealed edema of the bone marrow in the distal femur as well as joint effusion [Figure 1C]. Meanwhile, the skin lesions increased in number and became larger, and some of the lesions ruptured and discharged pus[Figure 1D]. Bronchoscopy results revealed a neoplasm in the left lingular bronchus (B4 + B5), and tissue biopsy reported suspicious spore-like substances. Because of the difficulty of diagnosis, the patient was transferred to the Respiratory Department, First Affiliated Hospital, School of Medicine, Zhejiang University on May 28th, 2018. On admission, we thoroughly reviewed his medical history and learned that he had lived in Vermont, which is located in the northeastern United States. For 4 years, the patient had not traveled outside Vermont. Physical examination findings included a low fever of 37.8°C, positive floating patella test in the left knee joint, and clusters of skin lesions, presenting as swellings, pustules, ruptures, and incrustations on the lower limbs. No abnormal breathing sounds or rales were heard. Laboratory findings showed the following: WBC count 17.2 × 10⁹/L, neutrophils 89.9%, CRP 218.5 mg/dL, ALT 214 U/L, and AST 93 U/L. The TSPOT.TB assay, (1, 3)-β-D-glucan assay, galactomannan assay, and Cryptococcus capsular polysaccharide antigen latex agglutination test all showed negative results. Ultrasonography revealed no organic lesions in the liver and gallbladder. We initially considered the diagnosis to be the hematogenous spread of a gram-positive bacteria, for example, methicillin-resistantStaphylococcus aureus, and prescribed linezolid injection of 600 mg every 12 h initially. The histologic section of the bronchus mucous membrane was obtained from the former hospital for examination, and yeast spores with thick and doubly refractile cell walls were found [Figure 1F]. An articular puncture was performed right after transferring, and a total of approximately 25 mL of light brown bloody fluid was obtained. The joint effusion and skin pus drawn from the ruptured rash were sent for culture and smear. The fluorescence-stained microscopic examination revealed round spores scattered in both the joint effusion and skin pus [Figure 1G]. After reviewing the literature and taking all these clinical characteristics into account, we considered that this was probably a case of an imported, disseminated fungal infection endemic to North America and that it could be blastomycosis or coccidioidomycosis. To confirm our speculation, the skin pus was sent for pathogen detection based on next-generation sequencing (NGS) technology (PMseq^TM, BGI, Shenzhen, China), and 57 sequences uniquely corresponding toBlastomyces dermatitidiswere identified. One week later, white and glabrous fungal colonies gradually appeared on a Sabouraud medium cultured with skin pus [Figure 1H]. Hence, the diagnosis of disseminated blastomycosis was established. On the third day after transferring, we started this patient on empirical anti-fungal treatment with oral posaconazole suspension, 400 mg twice per day for 12 days and subsequently, 200 mg three times per day because of further elevated liver enzymes (ALT 886 U/L). A follow-up chest CT scan revealed significant radiographic resolution after a 10-day anti-fungal therapy. Clinical symptoms, such as cough and knee joint pain, greatly improved, clusters of pustules on lower the limbs shrunk, and the ruptured pustules began to crust. The patient was discharged after 3 weeks with continuation of posaconazole prescribed. Follow-up monthly visits showed improved physical ability, further absorption of pulmonary effusions, and slightly elevated liver enzymes. The patient took posaconazole continuously for approximately 9 months.

To the Editor:A 66-year-old man complaining abdominal pain and bloating for 1 month was admitted to the Department of General Surgery of Xuanwu Hospital, Beijing, China. The patient had a normal body temperature and did not have symptoms such as nausea, diarrhea, or bone/joint pain. He had no history of allergies, no particular past medical or family history. He had taken no medications that could cause eosinophilia. No parasites were found in the stool. Abdominal computerized tomography (CT) scan showed thickening of the stomach wall and peristaltic stiffness with the swelling of the surrounding lymph nodes, indicating possibility of gastric cancer [Figure 1A]. Biopsy from gastroscopy showed a massive eosinophil infiltration of the stomach wall [Figure 1B]. Meanwhile, blood test showed white blood cell (WBC) count was elevated to 11.09 × 10⁹/L, eosinophils were elevated to 2.53 × 10⁹/L, hemoglobin 160 g/L, and platelet 269 × 10⁹/L. A bone marrow biopsy showed normal cellularity with increased eosinophils. breakpoint cluster region/c-abl oncogene 1, non-receptor tyrosine kinase and Fip1-like1 and platelet-derived growth factor receptor alpha fusion genes were not detected. He was diagnosed as hypereosinophilic syndrome (HES) and treated with corticosteroids (prednisone 20 mg, oral, twice per day). The patient’s abdominal pain and bloating symptoms gradually reduced, and the total number of eosinophils was back to normal in 2 weeks. The follow-up gastroscopy performed at 3 and 6 months after treatment showed normal stomach wall [Figure 1CandFigure 1D]. The corticosteroid was tapered and stopped after 8 months treatment.

To the Editor:Pancreatic cancer is one of the leading causes of cancer death worldwide. The significant symptoms prompting diagnosis often appear once the tumor invades surrounding tissues or metastasizes, resulting in the late diagnosis and the infeasibility of complete resection. For the patients at advanced stage, the shortage of efficient medication for systemic therapy further limited their survival time. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), possesses several documented mechanisms of action, including the inhibition of base excision repair as well as trapping of PARP.^[1]These mechanisms inhibit the repair of single-stranded break (SSB) and therefore lead to the induction of doublestranded break (DSB). Tumors with severe defect in homologous recombination-DNA damage repair (HRDDR) are ineffective in repair of DSB, which is theoretically susceptible to PARPi therapy.ARID1A, a part of the large ATP-dependent chromatin remodeling complexSNF/ SWI, is required for transcriptional activation of genes normally repressed by chromatin. Both truncating mutation and loss of copy number may lead to the shortage of functionalARID1Aprotein, causing HR-DRR deficiency that associates with the response to PARPi. Preclinical studies showed the loss ofARID1Amay sensitize cancer cells to PARPi.^[2]However, no relevant trial or case report of pancreatic ductal adenocarcinoma (PDAC) was published to date. Here we present the report of a PDAC patient with deleteriousARID1Amutation (p.Q1327*) who remained response to olaparib-based therapy for more than 13.0 months.

To the Editor:A 37-year-old Chinese woman, a nonsmoker, presented with adenocarcinoma of the left lung(stage IV) [Figure 1A], malignant pleural effusion, and multiple bone metastases in December 2014. Deoxyribonucleic acid sequencing of the tumor biopsy revealed an epidermal growth factor receptor (EGFR)exon 19 deletion, and treatment with gefitinib was consequently initiated in December 2014. There were no treatmentrelated side effects except for a grade 1 rash, and stable disease was achieved. Unfortunately, the patient did not experience long-term benefits and developed disease progression after only two months. A follow-up examination showed that extracranial disease and a small intracranial lesion had developed gradually. The patient then received whole-brain radiotherapy (30 Gy in ten fractions) and four cycles of single-agent pemetrexed in April 2015. Stable disease was achieved, which coincided with an improvement in the patient’s cough, shortness of breath, and general condition. The chemotherapy course was changed to two cycles of pemetrexed combined with cisplatin. A partial response (PR) was achieved, and the patient was treated with 14 cycles of pemetrexed alone as maintenance chemotherapy. The follow-up evaluations showed the patient’s condition to be stable; however, the patient’s disease progressed after 23 months. A computed tomography (CT) scan in March 2017 revealed that both the lung lesion and the malignant pleural effusion had increased in size [Figure 1B]. The subsequent biopsy specimen was subjected to next-generation sequencing(NGS) and a Syndecan 4-c-ros oncogene 1 (SDC4-ROS1)rearrangement was detected [Figure 1C]. The patient then received crizotinib in April 2017, and a PR was achieved[Figure 1D]. A CT scan done in August 2018 indicated the progression of the primary lesion in the left lung and malignant pleural effusion. However, the growth of the remaining lesions remained stable.

To the Editor:Hereditary hemochromatosis (HH) is a lateonset autonomic disease characterized by enhanced intestinal absorption of iron and iron overload, which may lead to liver cirrhosis, cardiomyopathy, diabetes, arthritis, and skin pigmentation. In 1996, Federet al^[1]cloned the gene responsible for HH (HFE) and reported that 85% of HH patients were homozygous for theC282Ymutation in theHFEgene. This was subsequently termed type 1 HH. Other inherited forms of HH exist that are nonHFE-related, an example of which is juvenile hemochromatosis (JH); two genotypes that induce JH have been reported thus far. One JH genotype involves the hemojuvelin gene (HJV), which was cloned from a Greek family with JH by Papanikolaouet al^[2]and is known as type 2A HH. The other involves the human antimicrobial peptide (HAMP) gene, which encodes hepcidin and is termed type 2B HH.

To the Editor:Coronary heart disease (CHD) and depression are common in patients worldwide and have a high comorbidity rate. Researches on depression have shown that it has been linked with long-term risk for CHD.^[1]The incidence and mortality of depression with CHD were higher, and the prognosis was worse.^[2]The association between CHD and depression is well established and is suggested to be bidirectional.^[3]Therefore, to provide possible conditions for the study of depression with CHD in the future, establishing a reliable animal model of depression with CHD is necessary. Chronic unpredictable mild stress (CUMS) is the most widely used to establish an animal model of depression for the past few years. Feeding a high-fat diet (HFD) to rats is a widely used method for establishing a model for atherosclerosis and CHD. Research reported that female cynomolgus monkeys that were housed in single cages and consumed an atherogenic diet could develop depression combined with CHD model.^[4]Another paper reported that CUMS combined with HFD in rats was similar to the clinical manifestation of vascular depression in humans.^[5]The former demonstrated that housing in single cages and feeding an atherogenic diet in monkeys could establish a depression combined with CHD model, the latter demonstrated that CUMS combined with HFD in rats was similar to vascular depression. It remains unclear whether CUMS combined with HFD in rats could establish a complex rat model of depression with CHD. Consequently, the aim of this study was to explore whether CUMS combined with HFD in rats could establish a representative, reliable rat model of depression with CHD and to provide possible conditions for an in-depth study of depression with CHD.

To the Editor:In a paper published in your October 2018 edition, Balkac and Ergun provided an overview of the developing role of infographics in healthcare.^[1]They noted that infographics have been defined by Smiciklas as data visualizations that attempt to relay complex information to an audience in a way that can be easily understood.^[2]