2020年 · 第133卷第12期

On March 11, 2020, the World Health Organization announced that the current outbreak of coronavirus disease 2019 (COVID-19) is a global pandemic.^[1]COVID-19, an acute respiratory contagious disease to which all people seem to be susceptible, is caused by 2019 novel coronavirus (2019-nCoV). The patient zero for this pandemic is unknown. Early epidemiology estimates suggest that the basic reproduction number (R0) for COVID-19 is 2.3, with a serial interval of 7.5 days.^[2]Chinese doctors and scientists issued warnings of a global pandemic at the initial phase.^[3]Unfortunately, the disease spread widely. Outbreaks and numerous new COVID-19 cases are reported daily around the world, causing public panic. To April 18, 2020, there have been more than 2,200,000 confirmed cases and 150,000 death cases reported globally.^[4]

Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.

From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.

Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.

LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort.

Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis.

The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271-3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345-1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314-1.875, P= 0.013).

Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.

It is a challenge to characterize the consciousness level of patients with severe disturbance of consciousness and predict their prognosis effectively for Chinese doctors. We aimed to investigate the psychometric property and the diagnostic practicality of severe disturbance of consciousness by Chinese Nanjing persistent vegetative state scale (CNPVSS) which was first set up in 1996 and modified in 2001 and 2011.

The concurrent validity, inter-rater consistency and diagnostic accuracy of CNPVSS and Chinese version of coma recovery scale-revised (CRS-R) were investigated by assessment of 380 patients with severe disorders of consciousness.

Total scores of the CNPVSS were correlated significantly with that of the CRS-R, indicating acceptable concurrent validity. Sub-scale analysis showed moderate to high inter-rater reliability and test-retest reliability. CNPVSS was superior to CRS-R on the diagnosis sensitivity. The CNPVSS was able to distinguish 65 patients in emergence from minimal consciousness state who were misclassified as in minimal consciousness state (MCS) by the CRS-R, and it could also distinguish two patients in MCS who were misclassified as in vegetative state by the CRS-R.

The CNPVSS is an appropriate measurement and is sensitive to distinguish the MCS patients from the VS patients.

The relationship of uric acid (UA) with the thyroid function among healthy individuals remains unclear. We aimed to examine the relationship between UA contents and thyroid hormone levels in healthy Chinese individuals.

This was a cross-sectional study of 1186 Chinese adults (736 men and 450 women) who underwent a health check-up at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) between January 1, 2010 and July 31, 2018. Clinical and thyroid hormone levels were compared in different UA groups (in male and menopause women groups, MG1: UA < 5 mg/dL; MG2: 5 mg/dL ≤ UA< 7 mg/dL; and MG3: UA ≥ 7 mg/dL; in female groups, FG1 to FG3 represent the UA levels of <4 mg/dL, 4 mg/dL ≤ UA< 6 mg/dL, and ≥6 mg/dL, respectively). In addition, natural cubic spline regression, together with Pearson correlation analysis, was performed in investigating the correlation of UA with thyroid hormones.

After adjusting for confounding factors, low levels of UA (for males, UA < 5.30 mg/dL; for females, UA < 4.05 mg/dL) were negatively correlated with free triiodothyronine (FT3) both in men and women. UA levels between 4.83 and 6.06 mg/dL may act to protect FT3 in women, while UA levels between 6.39 and 7.09 mg/dL may protect FT3 in men. FT3 levels of low-range UA group reduced compared with mid-range UA and the high-range UA groups in both men and women.

Our results provide epidemiologic evidence to support the negative correlation between low UA contents and FT3 in the Chinese Han population, suggesting that the reduced UA contents may serve as the risk factor to predict poor thyroid function in Chinese individuals.

Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.

CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.

Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.

Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

Catheter ablation is effective in restoring sinus rhythm and left atrial appendage closure (LAAC) is increasingly used for stroke prevention in patients with atrial fibrillation (AF). We aimed to observe the feasibility and safety of performing AF ablation and LAAC in a single (one-stop) procedure.

Consecutive AF patients who underwent the combined procedure of AF ablation and LAAC with WATCHMAN device between March 2017 and September 2018 were prospectively enrolled. Baseline and intra-procedural parameters were evaluated. Three-month and subsequent 1-year follow-up were performed in all and earlier-enrolled subjects, respectively.

A total of 178 AF patients (94 males, 68.9 ± 8.1 years) underwent the one-stop procedure with CHA₂DS₂-VASc score 3.3 ± 1.5 and HAS-BLED score 1.6 ± 1.0, respectively. Pulmonary vein isolation was achieved in all patients while additional linear ablation was applied if the operator deemed necessary, yielding immediate ablation success rate of 98.9% (176/178). In the subsequent LAAC, satisfactory seal (residual leak <5 mm) was achieved in all patients. One stroke and four cardiac perforations occurred peri-operatively. At 3-month follow-up, sinus rhythm and satisfactory seal were maintained in 153/178 (86.0%) and 178/178 (100%) patients, respectively. One stroke and one delayed cardiac tamponade occurred, while no device-related thrombus or device migration was observed. During the 1-year follow-up for the earlier enrolled subjects, 52/72 (72.2%) of the patients maintained sinus rhythm. There was no stroke or systemic embolism observed.

Combining catheter ablation and LAAC in a single procedure can be successfully and safely performed in non-valvular AF patients of Chinese population.

Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA₂r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA₂r in the activation of PSCs induced by 8-epi-prostaglandin F_2α (8-epi-PGF_2α).

TxA₂r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF_2α (10^-6, 10^-7, 10^-8 mol/L) for 48 h, and SQ29548 (10^-4, 10^-6, and 10^-7 mol/L), a TxA₂r-specific antagonist, for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10^-4 mol/L) for 2 h, followed by 10^-7 mol/L 8-epi-PGF_2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student’s t test.

TxA₂r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF_2a significantly increased mRNA levels of α-SMA (10^-6 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t= 10.70, P < 0.001; 10^-7 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t= 10.83, P <0.001; 10^-8 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t= 11.40, P < 0.001) and collagen I (10^-6 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10^-7 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10^-8 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10^-4 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10^-6 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10^-7 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t= 15.41, P < 0.001) and α-SMA (10^-4 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t= 15.17, P < 0.001; 10^-6 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t= 11.29, P < 0.001; 10^-7 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t= 12.86, P < 0.001). After being treated with SQ29548 (10^-4 mol/L) and then 8-epi-PGF_2α (10^-7 mol/L), the mRNA levels of a-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t= 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group.

The results show that 8-epi-PGF_2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF_2α. The result indicated that TxA₂r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF_2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.

Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence.

Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1β (IL-1β) was injected intraperitoneally to induce colitis recurrence.

Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ± 3.46% to 162.89 ± 11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ± 9.29% to 296.23 ± 30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ± 8.45% vs. 162.89 ± 11.45%, P = 0.0059) and Sal B (104.27 ± 6.09% vs. 162.89 ± 11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ± 89.42% vs. 296.23 ± 30.78%, P = 0.0028) but not influenced by SASP (285.23 ± 41.04% vs. 296.23 ± 30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1β in Sal B-treated group was significantly lower than that in SASP-treated group.

These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.

Metformin, one of the most widely used oral hypoglycemic agents in the world, plays an important role in treating type 2 diabetes for decades, and it has been recommended as a first-line drug in diabetes guidelines around the world because of the good efficacy and safety for monotherapy and combination therapy, evidence of health economic benefits, and definite clinical evidence in the prevention of cardiovascular complications.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and generally fatal fibrotic lung disease with a median survival of 2 to 3 years after diagnosis.^[1,2]Acute exacerbation of IPF (AE-IPF) is defined as an acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality. Nearly 46% of deaths in IPF are caused by AE-IPF, and the median survival of patients with AE-IPF is approximately 3 to 4 months.^[3]Over the past 27 years, great efforts have been paid to find therapies that might work for patients with this condition. We herein summarize current therapies for patients with AE-IPF.

A living donor is by definition a healthy person without significant medical problems. However, procedures in-volved with donation expose living donors to risks from a number of complications and donor safety remains an issue of concern.^[1]Complications can affect the donor’s quality of life (QoL) to varying degrees and scales or questionnaires are commonly used to assess their QoL. Based on existing literature, we found three types of instruments for assessing living donors’ QoL: (1) generic instruments, (2) disease-specific instruments, and (3) self-developed instruments (scales, questionnaires, survey lists). Generic instruments (eg, 36-item short form health survey),^[2]may not adequately measure some specific problems and/or minor issues associated with the organ transplant surgery. Disease-specific instruments, (eg, chronic liver disease questionnaire), originally developed for use with particular diseases,^[3]may lack precision and comprehensiveness in assessing the QoL of donors from healthy individuals. Self-developed instruments can resolve some of the deficiencies associated with generic and disease-specific instruments.^[4,5]In China, there remains a lack of consensus with regard to an effective scale that is specific for assessing the QoL of living organ donors.

Ulinastatin (UTI), a broad-spectrum elastase inhibitor, can stabilize lysosomal membranes and inhibit the activation and release of various inflammatory cytokines caused by cardiopulmonary bypass (CPB).^[1,2]UTI has recently been considered to be an effective anti-inflammatory agent and has been widely used in clinical settings,^[3,4,5]but the optimal dose has not been defined. Therefore, we conducted a prospective, randomized, controlled trial involving 60 patients undergoing cardiac surgeries with CPB and investigated the serum levels of tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8), at different time points in order to evaluate the anti-inflammatory efficacy of high-dose UTI and explore the optimum dose.

To the Editor:The epidemic caused by 2019 novel coronavirus (2019-nCoV) has drawn public attention.^[1]Huge infected population and enormous economic loss make it the urgent public health event to deal with. Confirmatory test targeting virus RNA was established at the early stage of outbreak and then used for 2019-nCoV infection diagnosis.^[2]However, high risk of laboratory infection, high-qualified personnel, and strict operation condition hampered its application into primary hospitals and community clinics.^[3]In this study, the serum immunoglobulin (Ig) M and IgG antibodies were detected in 2019-nCoV confirmed cases of different stages. Furthermore, three different immunological assays, chemiluminescent immunoassay (CLIA), gold immunochromatographic assay (GICA), and enzyme-linked immunosorbent assay (ELISA) were used for IgM and IgG detection.

To the Editor:The complications of pheochromocytoma caused by barely controlled hypertension and the overproduction of catecholamine can reduce patients’ life expectancy and quality of life. Herein, we report a case of bilateral multiple renal infarctions on computed tomography (CT) scan related to pheochromocytoma, which achieved complete relief on follow-up after tumor removal. A 47-year-old male with a 3-year history of uncontrolled hypertension (the highest value recorded was 210/160 mmHg) and intermittent severe headache, pallor, and sweating presented to our hospital on April 15, 2014. He did not monitor his blood pressure regularly but occasionally took dihydropyridine calcium-channel blockers. There was no history of kidney disease, thromboembolic disease, or renal artery injury. On admission, physical examination showed a blood pressure of 160/80 mmHg. His heart rate was 90 beats/min, and his respiratory rate was 18 breaths/min. The urinalysis showed slight hematuria. A transient elevation in serum creatinine and blood urea nitrogen was noted, which normalized within 2 days after fluid replacement. The prothrombin time, activated partial thromboplastin time and D-dimer levels were all within the normal range [Supplemental Table 1, http://links.lww.com/CM9/A206], while the plasma level of epinephrine was 7829.60 (reference interval: 9.16-254.60) pg/mL and that of norepinephrine was 6121.70 (86.30-551.60) pg/mL. An abdominal CT revealed an 8.5 cm tumor on the right adrenal gland and multiple wedge-shaped perfusion defects on the bilateral kidneys [Figure 1A]. The echocardiogram showed no arterial thrombus, and a 24-h Holter study revealed no arrhythmia.

To the Editor: Parkinson disease (PD) is the second most common neurodegenerative disease, and is characterized by both motor and non-motor symptoms. The leucine-rich repeat kinase 2 (LRRK2) gene, characterized by different mutations among different populations, is well-known in both familial and sporadic PD. The frequency of the G2019S mutation is 20% to 40% in the Ashkenazi Jewish and North African Arab populations, while G2385R is a common risk factor associated with Asian populations. Research teams have found that G2385R is also associated with PD in the Chinese Han population, suggesting a clear contribution of this mutation to the Han population, but descriptions of clinical PD symptoms in the Chinese Han population are rare and warrant further G2385R genotype-phenotype analyses. Substantia nigra (SN) hyperechogenicity was determined by transcranial sonography (TCS) in PD patients. It is a risk marker for PD, and associated with altered microstructural changes in white matter, including those areas relevant for motor and limbic function. Previous studies ofLRRK2variants, especially the G2019S mutation, have explored potential associations between CaucasianLRRK2variants and SN hyperechogenicity,^[1,2,3]but few have addressed Asian populations. Here, we used TCS imaging to compare features of Han Chinese PD patients with and withoutLRRK2variants.

To the Editor:Diarrheal disease is characterized by loose, watery stools or the frequent need for a bowel movement, and infectious gastroenteritis is a major cause of diarrheal illness worldwide. Despite improvements in public health and the economy, diarrheal disease remains a major public health problem with an associated burden.^[1]Notably, most cases of infectious gastroenteritis are associated with contaminated food and water sources containing infectious agents. Many kinds of infectious pathogens, including bacteria (Escherichia coli,Salmonella,andShigella), viruses (Rotavirus, Adenovirus,andNorwalk), and protozoa (Giardia,Cyclospora,andIsospora), cause infectious gastroenteritis.^[2]A comprehensive clinical assessment of patients with infectious gastroenteritis is critical to establish an effective approach to the initial diagnostic tests and treatment. In addition to the clinical and exposure history, the stool characteristics of patients with infectious gastroenteritis can provide important clues to possible causes, but rapid and specific testing of the pathogen also contributes to the diagnosis of infectious gastroenteritis. Current pathogen testing methods, including stool culture, antigen detection, and ova and parasite microscopy, involve a number of procedures, and findings may take up to 2 to 3 days to become available. These methods also have limitations such as being labor-intensive, requiring certain laboratory staffing, training, and resource. What’s more, positive yield of bacterial pathogens is known to be very low. Previous studies have shown 2.4% to 32% positive rates in stool cultures and even lower rates in cultures from intensive care unit patients (0.1%).^[3]

To the Editor: To date, coronavirus disease 2019 (COVID-19) has spread all over the world. As the exact sources of the virus, the time of virus shedding after infection and viral propagation are still undefined, there are still great challenges in controlling the virus spreading and the treatment of infection. Rapid diagnosis of infection cases and early isolation are extremely important for the overall prevention and control work.^[1]Therefore, rapid diagnosis of infection cases and early isolation are extremely important for overall disease prevention and control.^[2]

To the Editor:It is reported that the patients with coronavirus disease 2019 (COVID-19) infection who were admitted to the intensive care unit (ICU) had longer prothrombin time and higher plasma D-dimer levels compared to those who were not admitted to the ICU. This indicates that these patients had a higher risk of thromboembolism. In addition, plasma tumor necrosis factor-α (TNF-α) levels in ICU patients were significantly higher than those in non-ICU patients, and plasma TNF-α levels, interleukin (IL)-1 levels and IL-8 levels in all infected patients were higher than normal.^[1]The high expression of these inflammatory cytokines indicates that there is an inflammatory response in infected patients, and the inflammatory response is more obvious in severe patients. The findings of thrombus formation and high levels of inflammatory cytokines in COVID-19 patients are consistent with those in severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) patients. Since 2019 novel coronavirus (2019-nCoV), SARS-CoV, and MERS-CoV are all coronaviruses, and their genomic sequences are similar,^[2]it can be considered that the thrombogenesis process of COVID-19 patients is similar to that of patients infected with other coronaviruses, as inflammatory factors cause hypercoagulability and lead to thromboembolism. In fact, opposite findings have been reported that there are no significant differences in prothrombin time, accompanied by or regardless of that in D-dimer levels between ICU and non-ICU patients.^[3,4]We consider this discrepancy as a result of the limited quantity of subjects, and thus believe that a larger sample size is needed for this study. Whether the significant difference is absent or present, it is of significance for clinicians to obtain a clear basic understanding of the relationship between coronavirus and coagulation function as well as the influence of inflammatory factors on this process to make clinical judgement, provide early preventive anti-coagulation therapy for COVID-19 patients and eventually reduce the risk of thromboembolism.

To the Editor:Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that lack specific antigen receptors and yet produce effective cytokines to match the T helper cell subsets.^[1]For the past decade, the discovery of these cells and research on this topic have revealed that ILCs are tissue resident cells that have multiple immune roles, such as regulating tissue inflammation, tissue remodeling and metabolic homeostasis, by the effector functions of their subsets and are involved in diseases such as asthma, allergic rhinitis, inflammatory bowel disease, and cancer. Various publications have sorted and summarized the research results in this field, but these reports were descriptive literature reviews and qualitative taxonomic research that cannot fully and objectively reflect the whole picture of ILC research. The purpose of this study to evaluate the development of ILC and explore the future prospects of this research by examining the evolutionary path of hotspots and the distribution of time and geographic region in ILC research.

To the Editor:Hyponatremia, defined as a serum sodium concentration <135 mmol/L, is the most common water-electrolyte imbalance in clinical practice. Hyponatremia can be a complication of other diseases (eg, heart failure, renal failure, pneumonia). Hyponatremia can be divided into three main classes: hypovolemic; euvolemic, hyper-volemic. The pathogenesis of hyponatremia including taking drugs such as water pills (diuretics) and some anti-depressants and pain medications; heart failure and kidney or liver disease, bouts of chronic, severe diarrhea or vomiting.

To the Editor:Thrombotic thrombocytopenic purpura (TTP) is a type of life-threatening thrombotic microangiopathy (TMA) clinically characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and symptoms of regional ischemia/infarction including neurologic dysfunction and renal insufficiency.^[1]Its diagnosis is confirmed by a low activity of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), a protease of von Willebrand factor (vWF), and a detectable level of its inhibitory autoantibodies. Most TTP patients suffer from acquired TTP secondary to infection, autoimmune diseases, pregnancy, drugs, and so on. However, acquired TTP is rarely the first manifestation of a solid tumor. Herein, we report a case of acquired TTP with underlying cholangiocarcinoma in an elderly woman treated with bortezomib.

To the Editor:An 80-year-old man presented to the Cardiology Department with substernal pain of 20 minutes duration on August 13, 2017. We reviewed the patient’s case history record, which included two transradial access interventions using 6F sheaths (11-cm-long, Cordis Corporation, FL, USA). On February 13, 2009, the patient had presented with an acute inferior wall myocardial infarction and underwent percutaneous coronary intervention (PCI) via the right radial artery. On February 19, 2009, the patient underwent a second intervention, also via right radial artery access, for an elective anterior descending branch PCI. The patient ceased smoking after the first PCI. At this admission, before the third intervention, the patient had a weak radial pulse, but his right hand was asymptomatic. An inverse Allen test showed capillary refill in his hand within 6 s when the ulnar artery was compressed. However, we had difficulty in puncturing the radial artery and we selected to proceed with a heart catheterization using the right ulnar artery access. We successfully implanted two stents into the patient’s circumflex artery via transulnar access. After the intervention, a forearm arteriogram was performed and we were surprised that radial artery occlusion (RAO) had occurred proximal to the radial artery, instead of near the puncture site. In addition, we detected good collateral supply for the occluded radial artery by the ulnar artery and interosseous artery [Figure 1A-C].