2020年 · 第133卷第10期

Heart failure (HF), which is a common and serious complication of diabetes, has received more attention in recent years. One reason for this focus on HF is that, with a large reduction in atherothrombotic events after acute myocardial infarction, HF is a relatively more frequently encountered cardiac outcome in patients with type 2 diabetes (T2DM). Another reason is the unexpected reduction in hospitalization for HF observed in cardiovascular outcome trials with sodium-glucose co-transporter-2 inhibitors (SGLT2is).^[1,2,3]These findings led to speculation by clinicians and researchers on whether more effort should be made to differentiate patients with diabetes at a high risk of developing HF.

Fourier transform infrared (FTIR) spectroscopy technique has not been used as a diagnostic tool for diabetes in clinical practice. This study was linked to structural changes in hemoglobin (Hb) in type 2 diabetes patients at higher levels of HbA₁C using FTIR spectroscopy.

Fifty-three diabetic patients from the Bahawal Victoria Hospital, Bahawalpur, Pakistan were categorized as group A (6% < HbA₁C < 7%; n = 25) and group B (HbA₁C ≥9%; n = 28). Another group (group N) of twenty blood samples was taken from healthy people from the Islamia University Bahawalpur, Pakistan. Data from all groups were collected from January 1, 2018 to March 31, 2019. The structure of Hb was studied by FTIR spectroscopy and impact of glucose on the fine structure of HbA₁C was estimated.

Hb secondary structure erythrocyte parameters were altered by changing glucose concentrations. From FTIR spectra of all three groups it was found that Hb structure was slightly altered in group A, but significantly changed in group B (P < 0.05). There was an increase in β-sheet structure and a reduction in α-helix structure at elevated levels of HbA₁C (group B) in type 2 diabetes.

We suggest that higher level of glycation reflected by increased HbA₁C might be a contributing factor to structural changes in Hb in type 2 diabetic patients. FTIR spectroscopy can be a novel technique to find pathogenesis in type 2 diabetes.

The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults.

A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations.

Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake.

Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.

Resting heart rate (RHR) is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients. Bisoprolol fumarate, a second-generation beta-adrenoreceptor blockers (β-blocker) is commonly prescribed drug to manage hypertension. The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease (CAD) patients from the CAD treated with bisoprolol (BISO-CAD) study who had comorbid hypertension.

We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study (n = 866), which was a phase IV, multination, multi-center, single-arm, observational study carried out from October 2011 to July 2015 across China, South Korea, and Vietnam. Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome (CCCO), the results were presented as adjusted odds ratio (OR) along with 95% confidence interval (CI) and adjusted P value.

A total of 681 patients (mean age: 64.77 ± 10.33 years) with hypertension from BISO-CAD study were included in the analysis. Bisoprolol improved CCCOs in CAD patients with comorbid hypertension, with RHR <65 and <70 beats/min compared with RHR ≥65 and ≥75 beats/min, respectively, in the efficacy analysis (EA) set. In addition, it lowered RHR in both intent-to-treat (ITT) and EA groups after 6, 12, and 18 months of treatment. Further, RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients (adjusted OR: 4.34; 95% CI: 1.19-15.89; P = 0.03). Also, events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR <69 beats/min in ITT patients.

Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence, improve CCCO without affecting their blood pressure.

Radical nephrectomy and thrombectomy is the standard surgical procedure for the treatment of renal cell carcinoma (RCC) with tumor thrombus (TT). But the estimation of intra-operative blood loss is only based on the surgeon’s experience. Therefore, our study aimed to develop Peking University Third Hospital score (PKUTH score) for the prediction of intra-operative blood loss volume in radical nephrectomy and thrombectomy.

The clinical data of 153 cases of renal mass with renal vein (RV) or inferior vena cava tumor thrombus admitted to Department of Urology, Peking University Third Hospital from January 2015 to May 2018 were retrospectively analyzed. The total amount of blood loss during operation is equal to the amount of blood sucked out by the aspirator plus the amount of blood in the blood-soaked gauze. Univariate linear analysis was used to analyze risk factors for intra-operative blood loss, then significant factors were included in subsequent multivariable linear regression analysis.

The final multivariable model included the following three factors: open operative approach (P < 0.001), Neves classification IV (P < 0.001), inferior vena cava resection (P = 0.001). The PKUTH score (0-3) was calculated according to the number of aforementioned risk factors. A significant increase of blood loss was noticed along with higher risk score. The estimated median blood loss from PKUTH score 0 to 3 was 280 mL (interquartile range [IQR] 100-600 mL), 1250 mL (IQR 575-2700 mL), 2000 mL (IQR 1250-2900 mL), and 5000 mL (IQR 4250-8000 mL), respectively. Meanwhile, the higher PKUTH score was, the more chance of post-operative complications (P = 0.004) occurred. A tendency but not significant overall survival difference was found between PKUTH risk score 0 vs. 1 to 3 (P = 0.098).

We present a structured and quantitative scoring system, PKUTH score, to predict intra-operative blood loss volume in radical nephrectomy and thrombectomy.

Patients carrying the HongKongαα (HKαα) allele and -α^3.7/ααα^anti-4.2 could be misdiagnosed as -α^3.7/αα by the current conventional thalassemia detection methods, leading to inaccurate genetic counseling and an incorrect prenatal diagnosis. This study was aimed to accurately analyze the genotypes of HKαα carriers and -α^3.7/ααα^anti-4.2.

Samples were collected in our hospital from July 2017 to October 2019. Twenty-four common types of Chinese thalassemia were screened by gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (RDB). Anti-4.2 multiplex-PCR was used to confirm carriers of the ααα^anti-4.2 duplication with -α^3.7 deletion. Two-round nested PCR and multiplex ligation-dependent probe amplification (MLPA) were applied to accurately identify and confirm their genotypes. For data analysis, we used descriptive statistics and Fisher’s exact tests.

Two thousand five hundred and forty-four cases were identified as thalassemia in 5488 peripheral blood samples. The results showed that α, β, and αβ compound thalassemia were identified in 1190 (46.78%), 1286 (50.55%), and 68 (2.67%) cases, respectively. A total of 227 samples from thalassemia patients were identified as -α^3.7/αα by Gap-PCR, and the genotypes of two samples were uncertain. There was a difference between Gap-PCR and combined groups (Gap-PCR combined with nested PCR and MLPA) in detecting HKαα (P < 0.05). Among the 229 patients, 20 patients were identified as HKαα carriers and one was identified as -α^3.7/ααα^anti-4.2 by two-round nested PCR and MLPA, including 15 patients with HKαα/αα, three with HKαα/αα and β-thalassemia coinheritance, one with HKαα/-^SEA, one with HKαα/-α^4.2 and β-thalassemia coinheritance, and one with -α^3.7/ααα^anti-4.2 and β-thalassemia coinheritance.

ααα^anti-4.2 and HKαα genotypes of patients carrying -α^3.7 need to be detected to reduce the misdiagnosis rate of patients carrying HKαα and -α3.7/ααα^anti-4.2 alleles. More accurate genetic counseling can be provided in the clinic using nested PCR combined with MLPA.

Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure. The present study aimed to determine the role of NPR-C in the development of salt-sensitive hypertension.

The Dahl salt-sensitive (DS) and salt-resistant (DR) rats were used in this study. Animals were matched according to their age and weight, and then placed on either a high-salt (HS, 8%) or a normal-salt (NS, 0.4%) diet for 6 weeks randomly using random number table. The systolic blood pressure (SBP), plasmatic sodium concentration (PL_Na), urinary sodium excretion (UV_Na), and serum creatinine concentration (Scr) were measured. The concentration of ANP in blood and tissues (heart and kidney) was detected by enzyme-linked immunosorbent assay. The expression of ANP, NPR-A, and NPR-C in kidney was evaluated with western blot analysis. Regarding renal redox state, the concentration changes in malondialdehyde (MDA), lipofuscin, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and nitric oxide synthase (NOS) in kidney were detected by a spectrophotometric method. The kidney damage was evaluated using pathological techniques and the succinodehydrogenase (SDHase) examination. Furthermore, after an intra-peritoneal injection of C-atrial natriuretic peptide (ANP)_4-23 (C-ANP_4-23), an NPR-C receptor agonist, the SBP, biochemical values in blood and urine, and renal redox state were evaluated. The paired Student’s t test and analysis of variance followed by the Bonferroni test were performed for statistical analyses of the comparisons between two groups and multiple groups, respectively.

The baseline SBP in all groups was within the normal range. At the end of the 6-week experiment, HS diet significantly increased the SBP in DS rats from 116.63 ± 2.90 mmHg to 162.25 ± 2.15 mmHg (t = -10.213, P < 0.001). The changes of SBP were not significant in DS rats on an NS diet and DR rats on an NS diet or on an HS diet (all P > 0.05). The significant increase of PL_Na, UV_Na, and Scr related to an HS diet was found in both DS and DR rats (all P < 0.05). However, significant changes in the concentration (t= -21.915, P < 0.001) and expression of renal ANP (t= -3.566, P = 0.016) and the expression of renal NPR-C (t = 5.864, P = 0.002) were only observed in DS hypertensive rats. The significantly higher desmin immunochemical staining score (t = -5.715, P = 0.005) and mitochondrial injury score (t = -6.325, P = 0.003) accompanied by the lower SDHase concentration (t= 3.972, P = 0.017) revealed mitochondrial pathologic abnormalities in podocytes in DS rats with an HS diet. The distinct increases of MDA (t= -4.685, P= 0.009), lipofuscin (t= -8.195, P= 0.001), and Nox (t= -12.733, P < 0.001) but not NOS (t = -0.328, P = 0.764) in kidneys were also found in DS hypertensive rats. C-ANP_4-23 treatment significantly decreased the SBP induced by HS in DS rats (P < 0.05), which was still higher than NS groups with the vehicle or C-ANP_4-23 treatment (P < 0.05). Moreover, the HS-induced increase of MDA, lipofuscin, Nox concentrations, and Nox4 expression in DS rats was significantly attenuated by C-ANP_4-23 treatment as compared with those with HS diet and vehicle injection (all P < 0.05).

The results indicated that the renal NPR-C might be involved in the salt-sensitive hypertension through the damage of mitochondria in podocytes and the reduction of the anti-oxidative function. Hence, C-ANP_4-23 might serve as a therapeutic agent in treating salt-sensitive hypertension.

Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown.

Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed.

Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 downregulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 downregulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9).

Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

Dysuria is one of the main symptoms of genitourinary syndrome of menopause, which causes serious disruption to the normal life of peri-menopausal women. Studies have shown that it is related to decrease of detrusor contractile function, but the exact mechanism is still poorly understood. Previous results have suggested that the sphingosine-1-phosphate (S1P) pathway can regulate detrusor contraction, and this pathway is affected by estrogen in various tissues. However, how estrogen affects this pathway in the detrusor has not been investigated. In this study, we detected changes of the S1P/RhoA/Rho associated kinases (ROCK)/myosin light chain (MLC) pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause.

Thirty-six female Sprague-Dawley rats were randomly divided into SHAM (sham operation), OVX (ovariectomy), and E groups (ovariectomy + estrogen), with 12 rats in each group. We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting, respectively. We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay. Finally, we compared results between the groups with one-way analysis of variance.

The components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased, as compared with SHAM group. The percent decreases of the components in the S1P pathway were as follows: sphingosine kinase 1 (mRNA: 39%, protein: 45%) (both P < 0.05), S1P (21.73 ± 1.09 nmol/g vs. 18.86 ± 0.69 nmol/g) (P < 0.05), and S1P receptor 2/3 (S1PR2/3) (mRNA: 25%, 27%, respectively) (P < 0.05). However, the protein expression levels of S1PR2/3 and the protein and mRNA levels of SphK2 and S1PR1 did not show significant differences between groups (P > 0.05). The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows: ROCK2 (protein: 41%, mRNA: 36%) (both P < 0.05), p-MYPT1 (protein: 54%) (P < 0.05), and p-MLC20 (protein: 47%) (P < 0.05), but there were no significant differences in the mRNA and protein levels of RhoA, ROCK1, MYPT1, and MLC20 (all P > 0.05). In addition, all of the above-mentioned decreases could be reversed after estrogen supplementation (E group vs. SHAM group) (all P > 0.05).

In this study, we confirmed that ovariectomy is closely associated with the down-regulation of the S1P/RhoA/ROCK/MLC pathway in the rat detrusor, which may be one mechanism of dysuria caused by decreased contractile function of the female detrusor during peri-menopause.

Pancreatic cancer (PC) is a highly deadly malignancy with few effective therapies. We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) plays in PC cells by targeting far upstream element binding protein 1 (FUBP1) via microRNA-26a-5p (miR-26a-5p).

SNHG6 expression was predicted by bioinformatics, followed by verification via reverse transcription quantitative polymerase chain reaction. Then, the interactions among SNHG6, miR-26a-5p, and FUBP1 were detected through online software analysis, dual luciferase reporter assay and RNA pull-down. After that, cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6, miR-26a-5p, and FUBP1 and their roles in PC cells. Finally, the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice. A t-test, one-way and two-way analysis of variance were used for data analysis.

Compared with that in normal tissues, SNHG6 was highly expressed in PC tissues (1.00 ± 0.05 vs. 1.56 ± 0.06, t= 16.03, P < 0.001). Compared with that in human pancreatic duct epithelial cells (HPDE6-C7), SNHG6 showed the highest expression in PANC-1 cells (1.00 ± 0.06 vs. 3.87 ± 0.13, t= 34.72, P < 0.001) and the lowest expression in human pancreatic cancer cells (MIAPaCa-2) (1.00 ± 0.06 vs. 1.41 ± 0.07, t= 7.70, P= 0.0015). Compared with the levels in the si-negative control group, SNHG6 (0.97 ± 0.05 vs. 0.21 ± 0.06, t = 16.85, P < 0.001), N-cadherin (0.74 ± 0.05 vs. 0.41 ± 0.04, t= 8.93, P < 0.001), Vimentin (0.55 ± 0.04 vs. 0.25 ± 0.03, t= 10.39, P < 0.001), and β-catenin (0.62 ± 0.05 vs . 0.32 ± 0.03, t= 8.91, P < 0.001) were decreased, while E-cadherin (0.65 ± 0.06 vs. 1.36 ± 0.07, t= 13.34, P < 0.001) was increased after SNHG6 knockdown or miR-26a-5p overexpression, accompanied by inhibited cell proliferation, migration, and invasion. SNHG6 overexpression exerted the opposite effects. SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p. Silencing SNHG6 blocked the growth of PC in vivo.

Silencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p, thus providing further supporting evidence for its use in PC treatment.

Aspirin has been widely used in primary prevention of atherosclerotic cardiovascular disease (ASCVD).^[1,2,3,4]Aspirin for primary prevention of ASCVD does not significantly reduce all-cause mortality or cardiovascular mortality, and the main benefit of aspirin for primary prevention of ASCVD is a significant reduction in non-fatal ischemic events including myocardial infarction, transient ischemic attack, ischemic stroke, and major cardiovascular events (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), whereas the main risk is a significant increase in non-fatal major bleeding events including gastrointestinal bleeding and intracranial hemorrhage.^[5,6,7,8]Obviously, it makes sense to prescribe aspirin for primary prevention only if the benefits clearly outweigh the risks. In Europe and the United States, the benefit-risk ratio of aspirin for primary prevention has gradually decreased compared to the past due to the wide application of other primary prevention measures such as blood pressure reduction, smoking cessation, and the use of statins. Three recent large-scale clinical trials have shown that aspirin has no net clinical benefit when used in low-risk populations.^{[9,10,11,12,13]}Therefore, aspirin must be used with caution in the primary prevention of ASCVD.

Electronic health (medical) records, which are also considered as patients’ information that are routinely collected, provide a great chance for researchers to develop an epidemiological understanding of disease. Electronic health records systems cannot develop without the advance of computer industries. While conducting clinical trials that are always costly, feasible and reasonable analysis of routine patients’ information is more cost-effective and reflective of clinical practice, which is also called real world study. Real world studies can be well supported by big data in healthcare industry. Real world studies become more and more focused and important with the development of evidence-based medicine. These big data will definitely help in making decisions, making policies and guidelines, monitoring of effectiveness and safety on new drugs or technologies. Extracting, cleaning, and analyzing such big data will be a great challenge for clinical researchers. Successful applications and developments of electronic health record in western countries (eg, disease registries, health insurance claims, etc) have provided a clear direction for Chinese researchers. However, it is still at primary stages in China. This review tries to provide a full perspective on how to translate the electronic health records into scientific achievements, for example, among patients with diabetes. As a summary in the end, resource sharing and collaborations are highly recommended among hospitals and healthcare groups.

To the Editor:Adrenal and gonadal function can be evaluated by analyzing steroid hormone levels in different age groups, especially adolescent girls. Liquid chromatography-tandem mass spectrometry (LC-MS/MS or high-performance LC [HPLC]-MS/MS) offers a combination of the physical separation capabilities of HPLC and the mass analysis capabilities of tandem MS, which improves sensitivity and specificity in measuring steroid hormone levels.^[1,2]This method is more sensitive, effective, specific, and homogenous than other methods for analyzing children’s steroid hormone levels in the clinic. Studies on the reference intervals of steroid sex hormones have more commonly performed with Caucasian subjects than with Chinese subjects.^[3]LC-MS/MS-based reference intervals for steroid hormones in China, especially for healthy girls, have not yet been reported. With LC-MS/MS becoming increasingly common, the establishment of reference intervals is growing more urgent. Here, we define appropriate reference ranges for pregnenolone, 17α-hydroxyprogesterone, corticosterone, dehydroepiandrosterone, androstenedione, and free testosterone.

To the Editor:Otogenic brain abscesses are one of the most severe complications of the suppurative otitis media. Although extensive use of antibiotics has significantly reduced the mortality and morbidity of otogenic brain abscesses over the past years, there are still substantial patient deaths due to cerebral hernia or brain abscess rupture. In these lethal cases, proper time and means to drain the abscess are very important for good outcomes. Herein, we describe the successful management of a young male patient with otogenic brain abscess and cerebral hernia using transmastoid middle skull base craniectomy and ultrasound-guided abscess aspiration.

To the Editor: A 13-year-old girl with Crohn disease (CD) from Shandong Province transferred to our inflammatory bowel disease (IBD) center during April 2013. Three months previously, the patient presented with hematochezia and fever, but antibiotic treatment was unsuccessful. After admission, a colonoscopy indicated manifestations of segmental lesions, cobble stoning, and stricture [Figure 1A]. Cytomegalovirus, Epstein-Barr virus,Clostridium difficile, and amoebae were excluded as possible causes. There were also no indications of Behcet disease, systemic vasculitis, or other autoimmune diseases. Our initial diagnosis was active severe CD (Vienna typing, A1L3B2). This study was approved by the Ethical Committee of First Hospital of Peking University (No. 2019153). An appropriate signed patient consent form was obtained.

To the Editor:A multicenter retrospective survey in China shows that the most common pulmonary fungal disease is pulmonary aspergillosis.^[1]The diagnosis of invasive pulmonary aspergillosis (IPA) remains challenging because of the high false-negative and false-positive rate of galactomannan (GM) test. Domestic research reports that the IPA misdiagnosis rate can be as high as 73%. Besides, GM is time consuming, making the diagnosis delayed.

To the Editor:We appreciate the interesting and attentive article titled "Predictive accuracy of serum total calcium for both critically high and critically low ionized calcium in critical illness," written by Huet al.^[1]The use of serum total calcium and its corrected value in predicting critical ionized calcium concentration in critical illness is controversial. Hence, the authors retrospectively searched the Medical Information for Intensive Care III database to determine whether the level of total calcium, either corrected for albumin or not, could predict critically high and low ionized calcium. The authors concluded that both uncorrected and corrected total calcium levels are unreliable indexes for predicting the critical values of ionized calcium in critical illness. It is fully believed that this article will provide a profound presentation of and supplement to the everlasting story of calcium state estimation by total calcium. To completely understand the story between total calcium and ionized calcium and comprehensively interpret the results regarding calcium in this manuscript, some issues should first be prioritized.

To the Editor:Rarely, ischemic colitis can also mimic a carcinoma during colonoscopy and on computed tomography (CT) imaging. During colonoscopy, an ulceration, a submucosal mass, and a narrowed colon segment with an ulcerated mucosa have all been described as mimicking this kind of cancer. Few reports have documented this type of mass-forming ischemic colitis variant.^[1,2,3,4]Here, we described two patients with ischemic colitis who presented with lesions mimicking colon cancer.

To the Editor:Glycemic variability (GV) has a significant influence on the outcome in critically ill patients.^[1,2,3,4]Diabetic status of the patient affects the relationship between GV and mortality; increased GV is a more potent risk factor for mortality among patients without diabetes mellitus (DM) than among patients with DM.^[5]This retrospective study of 1234 intensive care unit (ICU) patients was conducted to determine the significant factors that contribute to high GV and to assess the association between GV and outcome in critically ill patients.

To the Editor:Atherosclerosis is a chronic inflammatory disease that involves multiple types of immune cells. Adaptive immunity exerts diverse and profound effects on atherosclerosis. The effector phenotype of lesional T cells may affect lesion growth and stability. Regulatory T cells with anti-inflammatory properties have been reported in atherosclerotic plaques. The targets of suppression of regulatory T cells include naive and effector CD4⁺and CD8⁺T cells, dendritic cells, and macrophages. A new subset of B cells, with CD19⁺CD24^hiCD38^hiphenotype in humans, is becoming a hot issue in the field of autoimmunity such as systemic lupus erythematosus and arthritis.^[1]These regulatory B cells (Bregs) play important roles in immune system by regulating functions of effector and regulatory T cells. Bregs exhibit protective role by attenuating the neointimal formation of atherosclerosis through an interleukin 10 (IL-10) mediated mechanism in a experimental study.^[2]There have been few studies on human Bregs in atherosclerosis disease until now. In this study we aimed to investigate CD19⁺CD24^hiCD38^hiB cells in coronary artery disease (CAD) patients requiring coronary artery bypass graft (CABG) surgery.

To the Editor:Generalized pustular psoriasis (GPP) is a rare, life-threatening skin disease characterized by recurrent episodes of pustulation. Apremilast, a phosphodiesterase 4 (PDE4) inhibitor, is a relatively new drug for the treatment of moderate to severe plaque psoriasis. Herein, we reported a patient of recurrent GPP possibly triggered by apremilast.