2021年 · 第134卷第10期

In the past 10 years, immune-checkpoint inhibitors (ICIs), targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis, have altered the therapeutic landscape of non-small cell lung cancer (NSCLC) and have resulted in long-term survival benefits in a subset of patients. In this editorial, we focused on recent advancements and challenges of ICIs in patients with NSCLC.

Single-nucleotide polymorphisms (SNPs)-associated genes and long non-coding RNAs (lncRNAs) can contribute to human disease. To comprehensively investigate the contribution of lncRNAs to breast cancer, we performed the first genome-wide lncRNA association study on Han Chinese women.

We designed an lncRNA array containing >800,000 SNPs, which was incorporated into a 96-array plate by Affymetrix (CapitalBio Technology, China). Subsequently, we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals (5634 breast cancer patients and 6308 healthy controls). Additionally, in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene.

We identified a novel breast cancer-associated susceptibility SNP, rs11066150 (P_meta = 2.34 × 10^-8), and a previously reported SNP, rs9397435 (P_meta= 4.32 × 10^-38), in Han Chinese women. rs11066150 is located in NONHSAT164009.1 (lncHSAT164), which is highly expressed in breast cancer tissues and cell lines. lncHSAT164 overexpression promoted colony formation, whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle.

Based on our lncRNA array, we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle. These findings suggest a potential therapeutic target in breast cancer.

Diabetes mellitus (DM) is an important risk factor in the long-term outcomes of surgical revascularization. However, few studies have focused on patients with ischemic heart failure (IHF) and DM, and the results are controversial. This study aimed to evaluate the effect of DM on the long-term outcomes of IHF patients undergoing coronary artery bypass grafting (CABG).

In this propensity-matched study, data of IHF patients who underwent CABG in our hospital from January 2007 to December 2017 were analyzed. With a mean 73-month follow-up time, the patients were divided into two groups according to whether they had DM. The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, stroke, recurrent myocardial infarction, and revascularization.

There was no significant difference in all-cause mortality between the two groups (5.8% vs. 4.1%, P = 0.216). The incidence of main adverse cardiovascular and cerebrovascular events (MACCE) in the secondary endpoint was significantly higher in the DM group than that in the non-DM group (10.4% vs. 8.1%, P = 0.023).

DM can negatively affect the long-term outcomes of IHF patients undergoing CABG by significantly increasing the overall incidence of MACCE, though the long-term survival does not show a significant difference between the DM and non-DM patients.

Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH.

Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance).

Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t= 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1 .6 cm (P < 0.05, t= 3.083), the PD reached 2.4 ± 0.5 cm and 2.0 ± 0.6 cm (P < 0.05, t= 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference.

The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research.

ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.

One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.

HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log₁₀ U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log₁₀ U/mL P= 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P= 0.025), and Ishak fibrosis score (r= -0.292, P= 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = -0.263, P = 0.014) and HBeAg-negative patients (r= -0.291, P= 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r= 0.366, P= 0.001; r= 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log₁₀ U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005).

HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy.

Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1

Follistatin-like 1 (FSTL1) plays both pro-inflammatory and anti-inflammatory roles in the inflammatory processes. We investigated whether serum FSTL1 could predict the current anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV)-specific indices.

We randomly selected 74 patients with AAV from a prospective and observational cohort of Korean patients with AAV. Clinical and laboratory data and AAV-specific indices were recorded. FSTL1 concentration was determined using the stored sera. The lowest tertile of the short-form 36-item health survey (SF-36) was defined as the current low SF-36. The cutoffs of serum FSTL1 for the current low SF-36 physical component summary (PCS) and SF-36 mental component summary (MCS) were extrapolated by the receiver operator characteristic curve.

The median age was 62.5 years (55.4% were women). Serum FSTL1 was significantly correlated with SF-36 PCS (r = -0.374), SF-36 MCS (r = -0.377), and C-reactive protein (CRP) (r = 0.307), but not with Birmingham vasculitis activity score (BVAS). In the multivariable linear regression analyses, BVAS, CRP, and serum FSTL1 were independently associated with the current SF-36 PCS (β = -0.255, β = -0.430, and β = -0.266, respectively) and the current SF-36 MCS (β = -0.234, β=-0.229, and β= -0.296, respectively). Patients with serum FSTL1 ≥779.8 pg/mL and those with serum FSTL1 ≥841.6 pg/mL exhibited a significantly higher risk of having the current low SF-36 PCS and SF-36 MCS than those without (relative risk 7.583 and 6.200, respectively).

Serum FSTL1 could predict the current functional status in AAV patients.

Despite almost two decades of well-funded and comprehensive response efforts by the Chinese Government, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) remains a major problem in China. Yet, few studies have recently examined long-term trends in HIV/AIDS prevalence, incidence, and mortality at the national level. This study aimed to determine the prevalence, incidence, and mortality trends for HIV/AIDS over the past 28 years in China.

We conducted a descriptive, epidemiological, secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 data. To evaluate trends in prevalence, incidence, and mortality over the study period from 1990 to 2017, we calculated values for annual percentage change (APC) and corresponding 95% confidence intervals (CIs) using joinpoint regression analysis.

A significant increase in HIV/AIDS prevalence was observed for 1990 to 2009 (APC: 10.7; 95% CI: 10.4, 11.0; P < 0.001), and then remained stable for 2009 to 2017 (APC: 0.7; 95% CI: -0.3, 1.7; P = 0.1). A significant increase in HIV incidence was also observed for 1990 to 2005 (APC: 13.0; 95% CI: 12.6, 13.4; P < 0.001), and then a significant decrease was detected for 2005 to 2017 (APC: -6.5; 95% CI: -7.0, -6.1; P < 0.001). A significant increase in AIDS-related mortality rate was detected for 1990 to 2004 (APC: 10.3; 95% CI: 9.3, 11.3; P < 0.001), followed by a period of stability for 2004 to 2013 (APC: 1.3; 95% CI: -0.7, 3.3; P = 0.2), and then another significant increase for 2013 to 2017 (APC: 15.3; 95% CI: 8.7, 22.2; P < 0.001).

Although prevalence has stabilized and incidence has declined, AIDS-related mortality has risen sharply in recent years. These findings suggest more must be done to bring people into treatment earlier, retain them in treatment more effectively, actively seek to reenter them in treatment if they dropout, and improve the quality of treatment and care regimens.

Pre-operative non-invasive histological evaluation of hepatocellular carcinoma (HCC) remains a challenge. Tumor perfusion is significantly associated with the development and aggressiveness of HCC. The purpose of the study was to evaluate the clinical value of quantitative liver perfusion parameters and corresponding histogram parameters derived from traditional triphasic enhanced computed tomography (CT) scans in predicting histological grade of HCC.

Totally, 52 patients with HCC were enrolled in this retrospective study and underwent triple-phase enhanced CT imaging. The blood perfusion parameters were derived from triple-phase CT scans. The relationship of liver perfusion parameters and corresponding histogram parameters with the histological grade of HCC was analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal ability of the parameters to predict the tumor histological grade.

The variance of arterial enhancement fraction (AEF) was significantly higher in HCCs without poorly differentiated components (NP-HCCs) than in HCCs with poorly differentiated components (P-HCCs). The difference in hepatic blood flow (HF) between total tumor and total liver flow (ΔHF = HF_tumor -HF_liver) and relative flow (rHF = ΔHF/HF_liver) were significantly higher in NP-HCCs than in P-HCCs. The difference in portal vein blood supply perfusion (PVP) between tumor and liver tissue (ΔPVP) and the ΔPVP/liver PVP ratio (rPVP) were significantly higher in patients with NP-HCCs than in patients with P-HCCs. The area under ROC (AUC) of ΔPVP and rPVP were both 0.697 with a high sensitivity of 84.2% and specificity of only 56.2%. The ΔHF and rHF had a higher specificity of 87.5% with an AUC of 0.681 and 0.673, respectively. The combination of rHF and rPVP showed the highest AUC of 0.732 with a sensitivity of 57.9% and specificity of 93.8%. The combined parameter of ΔHF and rPVP, rHF and rPVP had the highest positive predictive value of 0.903, and that of rPVP and ΔPVP had the highest negative predictive value of 0.781.

Liver perfusion parameters and corresponding histogram parameters (including ΔHF, rHF, ΔPVP, rPVP, and AEF_variance) in patients with HCC derived from traditional triphasic CT scans may be helpful to non-invasively and pre-operatively predict the degree of the differentiation of HCC.

The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM.

We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated.

In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses" . The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses" . Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01).

There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.

For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.

A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People’s Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.

All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P < 0.001, P= 0.004, and P < 0.001, respectively) and worse LFS (P < 0.001, P= 0.017, and P < 0.001, respectively), and OS (P < 0.001, P = 0.009, and P < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.

This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

The optimal treatment for large impacted proximal ureteral stones remains controversial. The aim of this study was to evaluate the efficacy, safety, and potential complications of mini-percutaneous nephrolithotomy (MPCNL) and retroperitoneal laparoscopic ureterolithotomy (RPLU) in the treatment of impacted proximal ureteral stones with size greater than 15 mm.

A total of 268 patients with impacted proximal ureteral stones greater than 15 mm who received MPCNL or RPLU procedures were enrolled consecutively between January 2014 and January 2019. Data on surgical outcomes and complications were collected and analyzed.

Demographic and ureteral stone characteristics found between these two groups were not significantly different. The surgical success rate (139/142, 97.9% vs. 121/126, 96.0%, P = 0.595) and stone-free rate after 1 month (139/142, 97.9% vs. 119/126, 94.4%, P = 0.245) of RPLU group were marginally higher than that of the MPCNL group, but there was no significant difference. There was no significant difference in the drop of hemoglobin between the two groups (0.8 ± 0.6 vs. 0.4 ± 0. 2 g/dL, P = 0.621). The mean operative time (68.2 ± 12.5 vs. 87.2 ± 16.8 min, P = 0.041), post-operative analgesics usage (2/121, 1.7% vs. 13/139, 9.4%, P = 0.017), length of hospital stay after surgery (2.2 ± 0.6 vs. 4.8 ± 0.9 days, P < 0.001), double J stent time (3.2 ± 0.5 vs. 3.9 ± 0.8 days, P = 0.027), time of catheterization (1.1 ± 0.3 vs. 3.5 ± 0.5 days, P < 0.001), and time of drainage tube (2.3 ± 0.3 vs. 4.6 ± 0.6 days, P < 0.001) of MPCNL group were significantly shorter than that of the RPLU group. The complication rate was similar between the two groups (20/121, 16.5% vs. 31/139, 22.3%, P = 0.242).

MPCNL and RPLU have similar surgical success and stone clearance in treating impacted proximal ureteral stones greater than 15 mm, while patients undergoing MPCNL had a lower post-operative pain rate and a faster recovery.

Chronic total occlusion (CTO) is the complete obstruction of a coronary artery for >3 months, combined with thrombolysis in myocardial infarction (TIMI) flow grade 0. Percutaneous coronary intervention (PCI) is widely used to treat CTO but is less used than coronary artery bypass graft surgery (CABG).^[1]However, PCI for CTO may increase the exposure of patients and operating physicians to radiation compared with non-CTO PCIs,^[2]and higher radiation exposure is linked to long-term adverse outcomes.^[3]PCI operators are exposed to significantly less radiation than patients during each procedure; however, repeated exposure during a lifetime may cause health problems. Therefore, reducing the exposure of PCI cardiologists to radiation without compromising the surgical success rate and clinical outcomes of patients is crucial. A low frame rate (LFR) protocol and/or selective fluoroscopy image storage decreases the exposure of PCI operators and patients to radiation during PCIs. The objective of this study is to evaluate the safety and efficacy of an LFR protocol for managing CTO patients.

Coronavirus disease 2019 (COVID-19) arises from infection with the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).^[1]The susceptible population can be of any age and gender; thus, the disease threatens the health and life of everyone, including pregnant women. Pregnancy can influence the physiological function of various organs, and thus may affect the prognosis of many infectious diseases. For example, higher mortality rates and more complications were reported in pregnant patients infected with SARS-CoV than those in non-pregnant patients.^[2]

The ganglion impar block was first introduced in 1990 by Plancarteet al.^[1]Since then, several modified versions have been reported by Wemm and Saberski,^[2]Nebab and Florence,^[3]and Foye.^[4]They tried to reduce pain effectively by considering the anatomy of the ganglion impar and coccyx. There were differences in the strengths of each individual’s technique. However, owing to the anatomical diversity of the structure itself,^[5]it was difficult to determine which technique would be more effective. Radiofrequency ablation (RFA) developed in the ganglion impar block also faced this controversy. In this clinical background, we present a new technique to implement ganglion impar RFA. Written informed consent was obtained from the patient before the initiation of the study.

The incidence of allergic disease has increased rapidly in recent decades in both developed and developing countries.^[1]In China, pollen ofArtemisiais one of the most important outdoor allergen as reported by the first national pollen survey across all provinces.^[2]Artemisiapollen has been found to be an important cause of seasonal asthma.^[3]Artemisia vulgarisandArtemisia annuaare the most importantArtemisiaspecies in China.A. vulgarismainly grows in western regions, whileA. annuais abundant in the densely populated northern and eastern regions.^[4]Immunoglobulin E (IgE) antibodies play a key role in allergy diseases. They are synthesized and released by B cells and bind to high-affinity IgE receptors on mast cells or basophils.^[5]Once the patients are exposed to corresponding allergens, the effector cells will be triggered and then release its mediator, leading to an allergic inflammation.^[5]Allergen immunotherapy based on specific allergens to patients is considered a promising and effective treatment for allergic diseases.^[6,7]Therefore, identification of the IgE-binding allergens will improve the diagnosis of allergy diseases and application of immunotherapy. However, previous studies have mainly investigated pollen allergens fromA. vulgaris(Art v), such as Art v 1-6. As forA. annua(Art an), only two allergens have been identified as Art an 1 (defensin-like protein) and Art an 7 (putative galactose oxidase).^[4]Thus, it is important to study allergens fromA. annuapollens.

To the Editor:A 19-year-old Chinese woman presented with a coma after a traffic accident on August 22, 2019. After the injury, she was moved to Guangxi University of Traditional Chinese Medicine First Affiliated Hospital with a diagnosis of severe traumatic brain injury (sTBI) with cerebral herniation [Figure 1A] and underwent craniotomy evacuation of hematoma and decompressive craniectomy twice. The patient was transferred to the intensive care unit (ICU) two days after the surgery. She has been in a coma since sTBI, and her other medical histories were unremarkable. On physical examination at admission, with a Glasgow Coma Scale (GCS) of 3, her vital signs showed a temperature of 35.3°C, blood pressure of 151/128 mmHg, and pulse of 90 beats/min. Her pupils were 3.5 mm in diameter and reactionless. A surgical scar was observed on the right side of the skull, and the missing part of her skull measured 10 cm × 10 cm. Two drainage tubes were implanted in the epidural space. She had undergone a tracheotomy and was given sedation and ventilator breathing, with a peripheral oxygen saturation of 100% on 50% fraction of inspired oxygen. Pathological signs were negative, and corneal reflex could not be elicited. There was skin abrasion on her waist, buttocks, and left hand. Other physical examination findings were unremarkable. Laboratory work was significant, with a procalcitonin (PCT) of 0.688 μg/L, high-sensitivity C-reactive protein (CRP) of 48.04 mg/L, CRP of >10 mg/L, creatine kinase of 1259 U/L, interleukin 6 of 31.62 pg/mL, hemoglobin of 92.3 g/L, white blood cell count of 15.3 × 10⁹/L, neutrophil count of 14.24 × 10⁹/L, platelet count of 140.6 × 10⁹/L, and bilirubin of 4.8 μmol/L. Other laboratory findings were unremarkable. Computed to-mography (CT) scan of the head showed epidural and subdural hematomas and severe cerebral edema with loss of sulci/gyri differentiation [Figure 1B]. To reduce oxygen consumption and alleviate brain edema and secondary damage to the nervous system, we immediately placed the patient under targeted temperature management (TTM) in addition to standard treatments, including mechanical ventilation, neuro-nutrition, osmotherapy, and prophylactic antimicrobial therapy of sTBI. The device for TTM we supplied was an ARCTIC SUN® 5000 Temperature Management System (Bard Medical, USA). The initial target temperature was set at 35 to 36°C; we used a cooling blanket to achieve the goal temperature and a nasal probe to continuously monitor the brain temperature. Arteries ice compressions, alcohol bath, and antipyretic were also provided in case of non-ideal effects of the cooling device. At the same time, we provided propofol 50 mg and dezocine 2.5 mg every 1 h for continuous sedation and analgesia and atracurium 1 μg/kg every 1 min for intermittent muscle relaxation to reduce man-machine confrontation and muscle fibrillation. During the treatment, the patient’s vital signs were stable, and her body temperature was maintained in the ideal range; she was well adapted to the ventilator, the ventilation parameters were gradually decreased, the bispectral index (BIS) monitoring indicated that her consciousness was gradually regained, and the changes in PCT values showed no increased risk of infection. The trends in body temperature, PCT, and BIS during TTM are shown inFigure 1F. The epidural drainage tubes were removed on day 9 of admission and the incision healed well. The repeated head CT on day 4 [Figure 1C] and day 13 [Figure 1D] showed that the cerebral edema was alleviated gradually, and then the target temperature was set to 36 to 37°C; the patient was then weaned from the ventilator and sedative and analgesic drugs. The patient regained consciousness on day 15, and she received inpatient pulmonary rehabilitation and physical exercises on day 19. TTM was terminated on day 22 after repeat CT showed complete resolution of the brain edema [Figure 1E], and the tracheal tube was removed on day 29. During TTM, no serious muscle fibrillation, coagulation disorder, bleeding events, arrhythmia, hypotension, gastric retention, delayed wound healing, or other complications occurred. Continuous monitoring of coagulation indicators and platelet counts showed no abnormalities. The patient was able to pull herself to the standing position and was able to sit down on her own on day 36, after which she was transferred to the general ward. After a half month of rehabilitation, she was able to walk independently and complete activities of daily living and was discharged on October 17, 2019.

To the Editor: A 64-year-old Chinese man (65 kg) with fever and lymphadenopathy was admitted to the hematology department of the Peking University First Hospital. Before admission, he had had intermittent fever for the past 3 months with a body temperature high of 38.5°C. He had no accompanying discomfort and his temperature sometimes dropped to normal without drugs. One month before admission, he found several palpable enlarged cervical lymph nodes. Upon admission, a lymph node biopsy was conducted and the pathological diagnosis showed a nodular sclerosis, a subtype of classical Hodgkin lymphoma. Positron emission tomography/computed tomography (PET/CT) revealed (i) enlarged lymph nodes that were widely distributed within the body with high fructose diphosphate (FDG) uptake, (ii) high FDG uptake in the L2 vertebra, right sacrum, sciatica, and femoral neck with local partial bone destruction, and (iii) low-density foci in the right lobe of the liver with increased glucose metabolism. Unilateral bone marrow aspiration and biopsy showed no signs of lymphoma infiltration. Therefore, the patient was diagnosed as having classical Hodgkin lymphoma nodular sclerosis subtype, stage IV, group B. He was treated with the doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy regimen. PET/CT showed complete remission after two cycles of ABVD therapy. Therefore, the primary chemotherapy regimen was continued. However, the patient started to develop hyperthermia with abdominal pain and diarrhea 1 week after day 1 of the third cycle of ABVD therapy. The patient’s white blood cell count was 1.31 × 10⁹/L (reference range: 3.5-9.5 × 10⁹/L), hemoglobin count was 66 g/L (reference range: 130-175 g/L), platelet count was 17 × 10⁹/L (reference range: 125-350 × 10⁹/L), and neutrophil granulocyte count was 0.72 × 10⁹/L (reference range: 1.8-6.3 × 10⁹/L). Further, the patient’s C-reactive protein was 105 mg/L (reference range: <8 mg/L) and procalcitonin was 1.04 ng/mL (reference range: <0.5 ng/mL). A routine stool test showed 15 to 20 white blood cells per high power field, and an occult blood test showed positive. He was then diagnosed with a gastrointestinal tract infection; he was prescribed meropenem and granulocyte-colony stimulating factor and was given a platelet infusion. Diarrhea symptoms were gradually alleviated and his body temperature dropped to normal. However, he began to develop a mild to moderate fever and dyspnea 2 weeks later. Arterial blood gas analysis indicated a pH of 7.461 (reference range: 7.35-7.45), a partial pressure of oxygen of 36.6 mmHg (reference range: 80-100 mmHg), a partial pressure of carbon dioxide of 41.3 mmHg (reference range: 35-45 mmHg), a bicarbonate level of 28.2 mmol/L (reference range: 22-27 mmol/L), and an oxygen saturation of 62.2% (reference range: 92.0%-98.5%). Thoracic CT revealed a diffuse ground-glass density grid [Figure 1A]. A presumptive diagnosis ofPneumocystis cariniipneumonia (PCP) was considered because alveolar lavage was not available because the patient refused to undergo a bronchoscopy. Given that his estimated glomerular filtration rate was normal (70.97 mL·min^-1·1.73 m^-2), 1920 mg oral trimethoprim-sulfamethoxazole (TMPSMX) was prescribed four times a day. Because his brain natriuretic peptide had increased, oral torsemide 10 mg/day was given. Two days later, his pulse oxygen saturation increased to 95% in room air and his body temperature remained normal. However, on day 5, the patient’s estimated glomerular filtration rate decreased to 49.67 mL·min^-1·1.73 m^-2. He suddenly became delirious and spoke nonsense words and displayed dancing arms. Neurological examination showed no abnormalities. The blood glucose concentration was 1.7 mmol/L (reference range: 3.9-6.0 mmol/L). After receiving an immediate intravenous bolus of 40 mL 50% dextrose and continuous intravenous infusion of 5% glucose in normal saline, the patient recovered mentally. He reported no history of diabetes and did not receive any insulin or anti-diabetic drugs. All orals drugs except TMP-SMX were discontinued to avoid triggering another episode of hypoglycemia. Unexpectedly, the patient, despite continuous infusion of 10% dextrose, suffered a recurrent hypoglycemic attack characterized with deliration. As a result, an intravenous bolus of 50% dextrose was administered repeatedly every hour to maintain the appropriate plasma glucose level. Laboratory data during the hypoglycemia attack were as follows: plasma insulin was 115.3 μU/mL (reference range: 2.6-24.9 μU/mL), C-peptide was 19.55 ng/mL (reference range: 1.1-4.4 ng/mL), and morning cortisol and adrenocorticotropic hormone levels and thyroid function were normal. These results indicated that an excessive secretion of endogenous insulin caused the recurrent hypoglycemia. Therefore, TMP-SMX was suspected of causing the hypoglycemia. Over the following 2 days, TMP-SMX and torsemide were temporarily discontinued. Consequently, plasma insulin and C-peptide levels decreased to within the normal range. TMP-SMX therapy was restarted because of the lack of alternative drugs available to treat severe PCP in the mainland of China. To avoid the occurrence of hypoglycemia, the dosage of TMP-SMX was decreased to 1920 mg/d and blood glucose was closely monitored 5 times/d. Thereafter, hypoglycemia did not reoccur during clinical treatment. One month later, the chest CT showed that most of the pulmonary lesions had been absorbed [Figure 1B].

To the Editor:Most of the multiple primary malignancies are metachronous or involve more than one system, we instead describe a case with synchronous triple cancers involving one organ system.

To the Editor:The liver is one of the most vulnerable organs of metastatic tumors. A metastatic tumor of the liver is about 18 to 40 times more common than a primary liver tumor (LM). There are approximately 50,000 new ovarian cancer patients in China each year, and the annual mortality rate is approximately 40%.^[1]At present, the treatment for LM in malignant tumors includes surgical treatment and nonsurgical treatment. Nonsurgical treatment mainly includes systemic chemotherapy, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), etc.

To the Editor:Acne vulgaris is a common chronic inflammatory skin disease. It is the 8th most prevalent disease in the world. Among adolescents, more than 85% once suffered from acne.^[1]Moreover, according to the recent evidence,^[2]patients often experience great physical and mental stress especially among the college students, due to its recurrence and scars or post-inflammatory hyperpigmentation left after healing. In China, while there are many studies on acne among adolecents and young adults, most of them are hospital-based. Substantial selection bias may be introduced in these studies because patients with severer symptoms or signs of disease are more likely to seek medical care, and perceive more impaired quality of life. The epidemiologic data from population-based studies in China are still lacking. Our study aims to estimate the prevalence of moderate and severe acne in Chinese college students and assess its impact on the quality of life.

To the Editor:Tinnitus is the impression of sounds in the absence of external sounds. Tinnitus affects 10% to 15% of adults, and about 20% of those with tinnitus considered it bothersome.^[1]The impact of tinnitus is well-recognized in the general population and military veterans. Tinnitus reduces the quality of life by generating anxiety and concentration problems, impairing the ability to do intellectual work, making it difficult to sleep, and causing depression which, in severe cases, leads to suicide. The incidence of tinnitus is increasing as a result of the population aging, the pace of life accelerating, increased noise exposure from construction and entertainment activity, and increases in armed conflicts in some areas. However, there is an absence of studies concerning the exacerbation of tinnitus. The present study reports tinnitus aggravating data that address this gap, to prevent the occurrence of tinnitus-related comorbidities and improve the management of tinnitus.

To the Editor:Unilateral nevoid telangiectasia (UNT) is an uncommon cutaneous vascular disorder characterized by superficial telangiectasia distributed in a unilateral, linear pattern. It can be either congenital or acquired. The pathogenesis of UNT is unclear and most scholars thought that hyperestrogenic states play an important role in UNT. Pulsed-dye laser (PDL) therapy is a mainstream treatment option. Herein, we present a case of PDL-resistant UNT successfully treated with hemoporfin-mediated photodynamic therapy (HMME-PDT).

To the Editor: Simple hepatic cyst is a common reason for consultation with gastroenterologists and hepatologists. Although most patients have a benign course, some suffer from serious complications, such as intracystic infection, hemorrhage, and even rupture, or symptoms caused by severe oppression of the surrounding tissues and organs. Understanding the prevalence of, and characteristics of, and factors associated with simple hepatic cysts is helpful for better treatment of symptomatic patients. The reported prevalence of the disease varies widely, ranging from 2.5% to 18.0%, and most of them were based on hospital surveys.^[1,2,3,4]As an asymptomatic disease in most cases, simple hepatic cysts are usually discovered incidentally on abdominal imaging. Therefore, surveys based on hospital populations cannot represent true prevalence. Furthermore, due to the absence of healthy controls, surveys with hospital populations have been unable to identify associated factors for simple hepatic cysts.^[1,2,3,4]

To the Editor:Polycythemia vera (PV)^[1]is a chronic progressive myeloproliferative neoplasm (MPN) characterized by clonal proliferation of myeloid cells. This condition presents with a high number of abnormal erythrocytosis, leukocytosis, and thrombocytosis, which may lead to venous thromboembolism. Cerebral venous sinus thrombosis (CVST) is a rare presentation of PV in clinical practice. Symptoms of PV are often insidious during the onset, and a lack of specific clinical manifestations of CVST may lead to delayed diagnosis. To date, diagnosis and management of CVST in PV remain a challenge due to the low incidence and limited evidence. In this study, we presented five cases of PV withJAK2V617F mutation, and CVST was the first manifestation of PV. The detailed characteristics are summarized inTable 1. The Institute Ethics Committee of Xuanwu Hospital, Capital Medical University approved this study (approval number 2019119). The authors certify that they have obtained all appropriate patient consent forms.

To the Editor: Tracheobronchomalacia (TBM) is a type of disorder that is caused by malformation of cartilage; the malformation leads to a deformity of the trachea or bronchus, with a cross-sectional reduction of ≥50% during exhalation, due to primary or secondary reasons.^[1]The severity of TBM depends on the anatomical changes of airways, which are described as mild (50%-75% reduction), moderate (75%-90% reduction), and severe (>90% reduction).^[2]According to previous studies, a set of causes have been identified to be associated with TBM.^[3]Congenital airway malacia can be a part of many rare syndromes,^[4]including chromosomal defect syndromes,de novogenetic mutations, mucopolysaccharidoses, and inherited connective tissue disorders. In addition, some conditions, such as tracheoesophageal fistula, vascular rings, malformation of the cardiovascular system, vitamin D deficiency, and recurrent infections, are revealed as the secondary reasons for TBM. Therefore, for TBM patients, it is important to distinguish the etiologies of TBM, which help to guide therapeutic and nursing strategies.