2020年 · 第133卷第11期

The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19).

Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ² test or Fisher exact test as appropriate.

Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Z = 9.738, P < 0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, χ² = 22.105, P < 0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Z = 3.216, P = 0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, χ² = 60.905, P < 0.001) and expectoration (32.1% vs. 12.1%, χ² = 13.250, P < 0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Z= 10.625, P < 0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] × 10⁹/L, Z = 7.618, P < 0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] ×10⁹/L, Z= 8.037, P < 0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Z = 10.315, P < 0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Z= 5.242, P < 0.001). Alanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Z = 2.592, P = 0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Z = 7.308, P < 0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] μmol/L, Z = 6.478, P < 0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Z = 10.206, P < 0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Z = 1.219, P = 0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, χ² = 148.105, P < 0.001), acute cardiac injury (59.6% vs. 0.9%, χ² = 93.222, P < 0.001), acute kidney injury (18.3% vs. 0%, χ² = 23.257, P < 0.001), shock (11.9% vs. 0%, χ² = 14.618, P < 0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, χ² = 7.655, P = 0.006).

Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.

We aimed to describe and analyze the pre-hospital emergency medical service (EMS) in Beijing and provide information for the government and medical institutions to optimize EMS.

We collected all pre-hospital emergency data in Beijing from 2008 to 2017. The chief complaint in each case was classified according to the Medical Priority Dispatch System (MPDS). The sites’ administrative districts were determined through geo-encoding of addresses and then classified into four functional regions. We analyzed the demand for EMS, emergency response times (ERT), and disease spectrum for Beijing as a whole, and for each functional region.

A total of 4,192,870 pre-hospital EMS cases met the inclusion criteria, with a significant increase (P < 0.001) of 51.60% from 2008 to 2017. EMS demand was positively associated with population (r= 0.946, P < 0.001). The pre-hospital EMS demand rate was 1907.05 in 2008 and 2172.23 in 2017 per 100,000, with no significant change (P = 0.57). ERT increased significantly (P = 0.001), from 19.18 min in 2008 to 24.51 min in 2016. According to MPDS classifications, the demand for pre-hospital care increased for 14 diseases, remained stable for 19, and decreased for only 1 disease. Cases of injury-related disease increased significantly from approximately 90,000 in 2017, accounting for 20% of all pre-hospital EMS cases, and the demand rate decreased in the core region but increased in the sub-urban regions. Cases of heart problems and stroke/transient ischemic attack also increased significantly in the four functional regions, with the highest demand rate in the Core Functional Region.

More resources and effort should be devoted to pre-hospital EMS according to the increased pre-hospital EMS demand and prolonged ERT in Beijing over our 10-year study period. Changes in disease spectrum and differences between functional regions should also be considered.

Imprecise interpretation of coronary angiograms was reported and resulted in inappropriate revascularization. Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is a comprehensive system to evaluate the complexity of the overall lesions. We hypothesized that a real-time SYNTAX score feedback from image analysts may rectify the mis-estimation and improve revascularization appropriateness in patients with stable coronary artery disease (CAD).

In this single-center, historical control study, patients with stable CAD with coronary lesion stenosis ≥50% were consecutively recruited. During the control period, SYNTAX scores were calculated by treating cardiologists. During the intervention period, SYNTAX scores were calculated by image analysts immediately after coronary angiography and were provided to cardiologists in real-time to aid decision-making. The primary outcome was revascularization deemed inappropriate by Chinese appropriate use criteria for coronary revascularization.

A total of 3245 patients were enrolled and assigned to the control group (08/2016-03/2017, n = 1525) or the intervention group (03/2017-09/2017, n= 1720). For SYNTAX score tertiles, 17.9% patients were overestimated and 4.3% were underestimated by cardiologists in the control group. After adjustment, inappropriate revascularization significantly decreased in the intervention group compared with the control group (adjusted odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.73-0.95; P = 0.007). Both inappropriate percutaneous coronary intervention (adjusted OR: 0.82; 95% CI: 0.74-0.92; P < 0.001) and percutaneous coronary intervention utilization (adjusted OR: 0.88; 95% CI: 0.79-0.98; P = 0.016) decreased significantly in the intervention group. There was no significant difference in 1-year adverse cardiac events between the control group and the intervention group.

Real-time SYNTAX score feedback significantly reduced inappropriate coronary revascularization in stable patients with CAD.

Nos. NCT03068858 and NCT02880605; https://www.clinicaltrials.gov.

Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people.

A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations.

There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and premenopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = -14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H= 408.18, P < 0.001) but not in the pre-menopausal subjects (Z=-0.43, P= 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age.

Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.

Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical microscope. The present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma (VS), as an alternative to a binocular surgical microscope.

Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June 2018. The demographics and tumor characteristics (size, Koos grade, composition [cystic or solid mass]) were matched between the two groups of patients. The following outcome measurements were compared between the two groups: duration of surgery, volume of blood loss, extent of tumor resection, number of operating field adjustments, pre- and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery, complications and surgeons’ comfortability.

A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope (cases, n = 39) or a surgical microscope (control, n = 42). Patients in the two groups had comparable tumor location (P = 0.439), Koos grading (P = 0.867), and composition (P = 0.891). While no significant differences in the duration of surgery (P = 0.172), extent of tumor resection (P = 0.858), facial function (P = 0.838), and hearing ability (P = 1.000), patients operated on under an exoscope had less blood loss (P = 0.036) and a fewer field adjustments (P < 0.001). Both primary and assistant surgeons reported a high level of comfort operating under the exoscope (P = 0.001 and P < 0.001, respectively).

The compact high-definition two-dimensional exoscope system provides a safe and efficient means to assist in removing large VSs, as compared to a surgical microscope. After the acquaintance with a visual perception through a dynamic hint and stereoscopically viewing corresponding to the motion parallax, the exoscope system provided a comfortable, high-resolution visualization without compromising operational efficiency and patient safety.

The transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/β-catenin pathway plays an important role, notably with regard to TGF-β1. Recent studies have shown that 1α, 25-dihydroxyvitamin D₃(1α, 25(OH)₂D₃) inhibits TGF-β1-induced EMT, although the underlying mechanism have not yet been fully elucidated.

Alveolar epithelial cells were exposed to 1α, 25(OH)₂D₃, ICG-001, or a combination of both, followed by stimulation with TGF-β1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and β-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.

Both 1α, 25(OH)₂D₃ and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)₂D₃ suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001.

1α, 25(OH)₂D₃ synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear.

An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting.

The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.

PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.

Rectal cancer (RC) is a malignant tumor that seriously threatens human health. Long non-coding RNAs (lncRNAs) play a vital role in tumor regulation. Nevertheless, their exact expression features and functions remain obscure, and therefore was the aim of the current study.

We utilized the Affymetrix human GeneChip to screen differentially expressed profiles of lncRNAs and mRNAs from the cancer tissues and matched paracancer tissues of 6 RC patients. Gene Ontology (GO) and pathway enrichment analyses identified crucial functions and pathways of the aberrantly expressed mRNAs. We used quantitative real-time polymerase chain reaction to verify the significant expression differences of 11 candidate lncRNAs between the cancer and paracancer tissues. LncRNA-mRNA coexpression networks were built by calculating the Pearson correlation value to identify significant correlation pairs. Online bioinformatics tools GEPIA2, ONCOMINE, and PROGgeneV2 were used to mine the expression and prognosis of three crucial mRNAs and six verified lncRNAs. Competing endogenous RNA networks were constructed by predicting microRNA response elements and calculating free energy.

We found 1658 differentially expressed lncRNAs (778 up-regulated and 880 down-regulated) and 1783 aberrantly expressed mRNAs (909 up-regulated and 874 down-regulated). GO and pathway enrichment analyses revealed the vital functions of the differentially expressed mRNAs, including cell proliferation, cell migration, angiogenesis, and cellular response to zinc ion. The canonical signaling pathways mainly included the interleukin-17, cell cycle, Wnt, and mineral absorption signaling pathways. Six lncRNAs including AC017002.2 (P= 0.039), cancer susceptibility 19 (CASC19) (P= 0.021), LINC00152 (P= 0.013), NONHSAT058834 (P= 0.007), NONHSAT007692 (P= 0.045), and ENST00000415991.1 (P= 0.045) showed significant differences in expression levels between the cancer tissue and paracancer tissue groups. AC017002.2, NONHSAT058834, NONHSAT007692, and ENST00000415991.1 have not yet been reported in RC. The crucial mRNAs myelocytomatosis viral oncogene (MYC), transforming growth factor beta induced (TGFBI), and solute carrier family 7 member 5 (SLC7A5) were selected. AC017002.2 and LINC00152 were positively correlated with MYC, TGFBI, and cytochrome P450 family 2 sub-family B member 6 (All r > 0.900, P < 0.050). NONHSAT058834 was positively associated with MYC (r = 0.930, P < 0.001), and CASC19 was positively correlated with SLC7A5 (r= 0.922, P < 0.001).

This study offers convincing evidence of differentially expressed lncRNAs and mRNAs as potential biomarkers in RC.

High-flow nasal cannula oxygen therapy (HFNC) is a novel respiratory support technology and has been extensively applied in clinics in recent years. This therapeutic equipment mainly includes an air-oxygen blender, an active humidifier, a high-flow nasal cannula, and a connecting inspiratory circuit. It provides patients a humidified high-flow gas (8-80 L/min) with relatively stable oxygen concentration (21-100%), temperature (31-37°C) and performs oxygen therapy via a nasal cannula, which is very comfortable.^[1]Through inspiration of high-flow gases, HFNC can produce a certain level of positive end-expiratory pressure^[2]and wash the biological dead space of the upper respiratory tract.^[3]Gases with constant temperature and humidity provided through a high-flow nasal cannula can maintain the function of the mucociliary clearance system^[4]and reduce upper airway resistance and breathing effort of patients to improve gas exchange and partial ventilation functions.

Helicobacter pylori (HP) has been considered to be one of the primary causes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma since 1993. Low-grade gastric MALT lymphoma with HP is widely treated with HP eradication therapy, according to each specific clinical situation. However, several studies and guidelines indicate that the modified HP eradication therapy is also valid for HP-negative gastric MALT lymphoma. The aim of this study was to perform a meta-analysis of the clinical efficacy of the modified HP eradication therapy for gastric MALT lymphoma without HP.

We searched studies that reported the response rate of the modified HP eradication therapy regimen for gastric MALT lymphoma without HP by using PubMed, Medline, and Ebsco from January 1971 until February 2019. All statistical analyses were carried out using R 3.5.3 (Mathsoft Company, Cambridge, MA, USA). The pooled response rate was expressed as a decimal. The heterogeneity test was performed using the I-squared (I²) statistic.

A total of 14 studies were selected with a total of 148 patients with HP-negative gastric MALT lymphoma. The overall pooled response rate was 0.38 (95% confidence interval [CI]: 0.29-0.47). The combined estimate is I² = 57% (P < 0.01). The study subjects were categorized by factors (area of patients). The pooled response rate of the sub-groups (Korea, Japan, China, and Western countries) was 0.63 (95% CI: 0.50-0.76), 0.16 (95% CI: 0.05-0.30), 0.38 (95% CI: 0.20-0.55), and 0.57 (95% CI: 0.08-1.00). The response rate showed that the modified HP eradication therapy was effective for patients with HP-negative gastric MALT lymphoma, especially in Korea and Western countries.

Therefore, the modified HP eradication therapy can be considered an optional therapy for patients with low-grade HP-negative gastric MALT lymphoma. However, several limitations were revealed in the meta-analysis. Further systematic reviews and research are required.

Since the outbreak of coronavirus disease 2019 (COVID-19), the National Health Commission of the People’s Republic of China has issued a series of timely updated guidelines. The "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7)" was published on March 3, 2020 and was developed from the accumulated clinical experience and a deeper understanding of the disease.^[1]Compared to the sixth version, the contents on the transmission routes, pathological features, clinical characteristics, diagnosis, triage, treatment, and discharge standards have been revised in the latest edition. This article presents a brief interpretation of the seventh version for a better understanding of the protocol.

In December 2019, initial cases of the novel coronavirus (2019-nCoV) infection, termed coronavirus disease 2019 (COVID-19), were first reported in Wuhan, China.^[1]In humans, infections with the human coronavirus 229E, OC43, NL63, and HKU1 usually result in mild, self-limiting upper respiratory tract infections. However, other variants have rapid transmission rates and can cause severe respiratory syndrome and death. These variants include severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the current 2019-nCoV.

Hypertension, as the most common cardiovascular disease (CVD), occurs with a high morbidity. The disease attacked a population of about 1.13 billion in 2015 globally, and its prevalence exceeds 27.9% in Chinese aged >18 years.^[1]Unfortunately, lifestyle modifications and medical interventions fail to control the disease in a third of patients. Human gut microbiota can regulate immunity, inflammation, and metabolism. For decades, increasing evidence has shown that the activity and composition of microbiota are related to health status (like influencing blood lipid and glucose), which provides a new insight into the mechanism of hypertension.^[2,3]

Twin pregnancies have increased significantly over recent decades, mainly due to the growing rate of such pregnancies that have been achieved via assisted reproductive techniques. Twin pregnancies are associated with high infant morbidity and mortality. Maternal obesity has been found to be significantly related to an increased risk of pre-eclampsia and other adverse outcomes. Maternal weight gains during pregnancy may have important implications for maternal and fetus health. Women with excessive gestational weight gains (GWG) are more likely to increase their risk of gestational diabetes mellitus (GDM), macrosomia, preterm birth, and fetal growth restriction. As with singletons, GDM is also expected to be more frequent in pre-gravid obese mothers of twins.^[1]Although there are some guides for twin pregnancies, few researches are focused on the systematic management of twin pregnancies. The main goal of this study was to assess the benefits of systematic management of twin pregnancies, especially GDM-like diet and exercise management models.

Mitochondrial trifunctional protein (MTP) is a multienzyme complex, which catalyzes the last three steps of mitochondrial β-oxidation of the long-chain fatty acids. Structurally, MTP consists of four α-subunits and four β-subunits, which are encoded byHADHAgene (OMIM 600890) andHADHBgene (OMIM 143450), respectively. Mutations inHADHAorHADHBlead to varying degrees of decline in MTP activity, that in turn results in three types of clinical manifestations: a severe phenotype with neonatal onset, a hepatic phenotype with infantile onset, and a neuromyopathic phenotype with later onset.^[1]The neuromyopathic type is the mildest one, characterized by myopathy, sensorimotor neuropathy, and recurrent rhabdomyolysis.^[1,2]To the best of our knowledge, only 33 cases have been reported worldwide to date,^[1,2]of which there were only two cases (including Patient 3 of this study) in China.^[3]Here, we described three early-onset Chinese cases that not only showed neuromyopathy and rhabdomyolysis but also involved the central nervous system (CNS), which are uncommon in this phenotype.

Despite great progress in concepts and surgical technique, arch replacement remains a challenge for most cardiac surgery centers. The classic Sun’s procedure (total arch replacement using four-branched graft with stented elephant trunk implantation) has achieved good results in arch replacement in cases of type A aortic dissection and become the standard treatment for type A aortic dissection in our center.^[1,2]The branch-first technique has been reported by some surgeons. In most cases, the three arch branches were reconstructed under cardiopulmonary bypass (CPB) or deep hypothermia circulatory arrest. We began applying the branch-first Sun’s procedure 1 year ago.^[3]The three arch branches were bypassed without CPB in most patients. The lowest temperature at circulatory arrest was also elevated. Here we report our early experience with branch-first Sun’s procedure in both elective and emergency settings.

Gestational diabetes mellitus (GDM) manifests as different degrees of carbohydrate intolerance during pregnancy. According to several studies, GDM affects 4% to 25% of pregnant women. The majority of patients with GDM have varying levels of insulin resistance and chronic low-grade inflammation, which are related to vascular injury and dysfunction and subsequent platelet activation.^[1]Consequently, platelet activation may be closely related to GDM severity. The mean platelet volume (MPV) is one of the indexes used to evaluate platelet morphology and activity. An elevated MPV has been demonstrated to be related to cardiovascular diseases and other conditions, such as hypertension and nonalcoholic fatty liver disease.^[2]To our knowledge, few studies have demonstrated the relationship between the MPV and GDM. We aimed to evaluate the diagnostic value of the MPV for GDM in the first trimester.

Allergen immunotherapy is executed by the repeated administration of specific allergens to patients with allergic disorders to protect against allergic reactions. It is the only disease-modifying therapy for allergic rhinitis and asthma, and many clinical trials and meta-analyses have demonstrated its beneficial effects.^[1]Immunologic changes associated with immunotherapy are complicated, and the underlying mechanism needs further elucidation. Cluster immunotherapy is an improved immunotherapy with an accelerated build-up schedule that achieves symptom improvement earlier than the conventional way.^[1]This study aimed to investigate the early immune changes caused by cluster immunotherapy by employing transcriptomic profiling analysis and identifying candidate biomarkers for early evaluation of immunotherapy. Approval of the Peking Union Medical College Hospital Ethics Committee had been obtained (No. ZS-1917), and all the subjects had given written informed consent.

To the Editor: In a prospective, self-controlled, assessor-blinded, observational study, Wanget al^[1]evaluated the associations of ultrasound-measured indicators with difficult laryngoscopy. By the multivariate logistic regression analyses and the receiving operator characteristic (ROC) curve analysis, they concluded that the magnitude of the angle between the epiglottis and glottis under ultrasound was highly associated with difficult laryngoscopy. Furthermore, difficult laryngoscopy might occur when this angle was less than 50°. Given the facts that difficult airway remains one of main reasons for adverse outcomes of surgical patients receiving general anesthesia and no clinical indicator with high sensitivity can reliably predict difficult airway,^[2]their findings have potentially clinical implications. However, we noted some methodological issues in their study that would have made their findings questionable.

To the Editor:Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neuromuscular disease associated with the degeneration of both upper and lower motor neurons. It eventually leads to muscle weakness, atrophy, and death within 3 to 5 years, most commonly from respiratory failure. The appropriate anesthetic management of these patients, especially parturients pose various challenges to anesthesiologists.

To the Editor:Recent studies have shown that the morphology of bonein vivo,including the shape, diameter, length, curve, and alignment of the bone, adapt to longterm loads both before and after skeletal maturity. The deformation and rate are different according to the magnitude of strain, the mode of action, position and the quality of bone of the strain, which is named by law of dynamic deformation of bone.^[1]Here, we found that the existence of circular bone trabecula in the calcaneus by P45 plastination technology. It might be caused by the force conduction to the flexor digitorum brevis during the contraction of the triceps surae according to this law.

To the Editor:The polymyxin antibiotics colistin (polymyxin E) and polymyxin B (PMB) became available in the 1950s; thus, they did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infection.^[1]Multidrug-resistant (MDR) bacterial infections are primarily caused by gram-negative bacilli (GNB), such asPseudomonas aeruginosaandKlebsiella pneumoniae, in lung transplant (LT) patients.^[2]The increasing prevalence of MDR-GNB infections in LT patients has led to an upsurge in the use of these "older" drugs. During the treatment course, we should pay attention to severe and life-threatening respiratory paralysis caused by neuromuscular blockage associated with PMB. Herein, we report a rare case of a 67-year-old LT patient who suffered from respiratory arrest induced by PMB.

To the Editor:Keloids are a specific type of scar that exceeds the original wound boundary and unlikely to shrink spontaneously. Numerous methods for treating keloids have been reported, including surgical resection, radiation, injection, laser therapy, and cryotherapy. However, no single method can ensure a complete cure. Among the reported methods, the intralesional injection of steroids is widely used. A large number of studies have shown that the injection of glucocorticoids combined with 5-fluorouracil (5-FU) into the keloid can soften the texture, reduce the volume, and relieve the associated symptoms.^[1]The conventional intralesional injection was routinely performed by directly injecting the drug into the parenchyma through the surface of the keloid in a multipoint manner. However, the significant pain caused by this approach usually affects patient compliance. Moreover, it is difficult to evenly distribute the drug into the firm and tight fibrous structure, which may decrease the therapeutic effect. Accordingly, we modified the technique into a two-step operation, by first injecting into the keloid’s base and then injecting into the parenchyma.

To the Editor:In advanced head and neck malignancies, especially in patients who relapse after comprehensive treatment such as a history of neck surgery or radiotherapy, tumors can simultaneously invade both the mucosa and skin. Reconstruction of penetrating defects formed after tumor resection must achieve the following goals: (1) Reconstruction of the digestive tract to restore swallowing function. (2) Provide soft tissue for repair of important structures in the neck, that is, to re-build the skin of the neck. We used bilateral supraclavicular artery island flaps to repair a large area of skin with mucosal defects in the neck of a patient with advanced laryngeal malignancy after surgery, and with satisfactory post-operative results.

To the Editor:Syphilis is a sexually transmitted disease caused byTreponema pallidum (T. pallidum). Secondary syphilitic lesions usually occur within 3 months after the initial exposure toT. pallidum. The most frequent skin manifestations of secondary syphilis are macular and papular eruptions. However, other uncommon lesions, such as nodular, pustular, arcuate, and psoriasis-like lesions, have been occasionally reported.^[1,2]Annular syphilitic lesions are relatively rare and usually present as multiple lesions scattered over the body or are limited to local skin such as genital.^[1,3]Herein, we report a solitary annular lesion of secondary syphilis on the face.

To the Editor: Identifying the pathogen from clinical samples is crucial for the diagnosis of a newly emergent infectious disease, such as 2019 novel coronavirus (2019-nCoV), which has posed great threats to global public health.^[1]In some cases, despite the positive epidemiological, clinical, and radiographic evidence, coronavirus disease 2019 (COVID-19) diagnosis can still be restricted by inconclusive polymerase chain reaction (PCR) results.^[2]For samples of suspicious patients, where the fluorescence quantitative PCR (FQ-PCR) results in a few respiratory tract specimens were inconclusive, high-throughput sequencing (HTS) can be an effective confirmation method. Here, we report our experience of applying HTS to confirm a suspected 2019-nCoV infection.