2019年 · 第132卷第09期

Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.

This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.

In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ²=3.937, P=0.047), SDAI (χ²=4.666, P=0.031), and CliDR criteria (χ²=4.297, P=0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months, Z=-2.295, P=0.022).

The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.

Large-nerve fiber dysfunction, as assessed by vibration perception threshold (VPT) predicts risks of ulceration, amputation, and mortality in diabetes. Serum uric acid (UA) is closely associated with various metabolic disorders, especially diabetes. Thus, we sought to investigate the clinical relevance of UA to large-nerve fiber dysfunction, among patients with type 2 diabetes (T2D).

Medical records of consecutive patients with T2D who were admitted to Beijing Friendship Hospital Pinggu Campus between May 2014 and December 2016 were collected. Data for the 824 eligible patients included in the final analysis were extracted using a structured form. A VPT value ≥15 in either foot was defined as abnormal. We compared the clinical characteristics between patients with abnormal VPT and those with normal VPT (VPT value <15 in both feet) in the overall population and in gender subgroups. Logistic regression analysis was performed to explore the association of abnormal VPT with UA level. One-way analysis of variance was used to compare VPT values across four UA quartiles.

UA levels were significantly lower in T2D patients with abnormal VPT than in those with normal VPT (294.5 ± 84.0 vs. 314.9 ± 92.8 μmol/L, P < 0.01), especially among male patients (311.7 ± 85.2 vs. 336.9 ± 89.6 μmol/L, P < 0.01). From the logistic regression analysis, hyperuricemia (males >420 μmol/L; females >360 μmol/L) was associated with a reduced risk of abnormal VPT (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.39–0.91; P < 0.05). This association was robust in male patients (OR, 0.43; 95% CI, 0.24–0.76; P < 0.01) but not in female patients (OR, 0.92; 95% CI, 0.47–1.82; P = 0.816), even after adjustment for confounding factors. For the younger male subgroup (age <65 years), VPT values decreased as the UA level increased (P for trend = 0.002), but this trend was not significant in older male subgroup (age ≥65 years; P for trend = 0.400).

Low serum UA levels showed a significant association with an increased risk of large-nerve fiber dysfunction in male patients with T2D, but not in female patients with T2D. In addition, in only the younger subgroup of male patients (<65 years), lower levels of UA also correlated with higher VPT values.

It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage. The time taken for symptoms to spread from spinal or bulbar regions to both (time to generalization; TTG) is considered a strong predictor of survival; however, this has rarely been studied in Asian populations. The aim of this retrospective study was to evaluate potential factors affecting prognosis in Chinese patients with sporadic ALS, with a focus on the association between TTG and overall survival.

Seventy-one patients with sporadic ALS who were hospitalized at Chinese PLA General Hospital from 2009 to 2016 were followed up until December 2017. Survival analysis was performed using univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards models. The clinical data of the patients were recorded and analyzed. Variables studied were age at symptom onset, sex, site of symptom onset, diagnostic latency, TTG, diagnostic category, ALS Functional Rating Scale-revised score, percent predicted forced vital capacity (FVC%), and disease progression rate (DPR) at diagnosis.

The mean age at onset was 54 (SD = 10.2) years, and the median survival time from symptom onset was 41 months (95% confidence interval: 34–47). By univariate analysis, factors independently affecting survival were age at symptom onset (Log rank = 15.652, P < 0.0001), TTG (Log rank = 14.728, P < 0.0001), diagnostic latency (Log rank = 11.997, P = 0.001), and DPR (Log rank = 6.50, P = 0.011). In the Cox multivariate model, TTG had the strongest impact on survival time (hazard ratio = 0.926, P = 0.01).

TTG can be used as an effective indicator of prognosis in patients with sporadic ALS.

The mortality of cardiovascular disease is constantly rising, and novel biomarkers help us predict residual risk. This study aimed to evaluate the predictive value of serum homocysteine (HCY) levels on prognosis in patients with ST-segment elevation myocardial infarction (STEMI).

The 419 consecutive patients with STEMI, treated at one medical center, from March 2010 to December 2015 were retrospectively investigated. Peripheral blood samples were obtained within 24 h of admission and HCY concentrations were measured using an enzymatic cycling assay. The patients were divided into high HCY level (H-HCY) and low HCY level (L-HCY) groups. Short- and long-term outcomes were compared, as were age-based subgroups (patients aged 60 years and younger vs. those older than 60 years). Statistical analyses were mainly conducted by Student t-test, Chi-squared test, logistic regression, and Cox proportional-hazards regression.

The H-HCY group had more males (84.6% vs. 75.4%, P=0.018), and a lower prevalence of diabetes (20.2% vs. 35.5%, P < 0.001), compared with the L-HCY group. During hospitalization, there were seven mortalities in the L-HCY group and 10 in the H-HCY group (3.3% vs. 4.8%, P= 0.440). During the median follow-up period of 35.8 (26.9–46.1) months, 33 (16.2%) patients in the L-HCY group and 48 (24.2%) in the H-HCY group experienced major adverse cardiovascular and cerebrovascular events (MACCE) (P=0.120). History of hypertension (hazard ratio [HR]: 1.881, 95% confidence interval [CI]: 1.178–3.005, P=0.008) and higher Killip class (HR: 1.923, 95% CI: 1.419–2.607, P < 0.001), but not HCY levels (HR: 1.007, 95% CI: 0.987–1.027, P=0.507), were significantly associated with long-term outcomes. However, the subgroup analysis indicated that in older patients, HCY levels were significantly associated with long-term outcomes (HR: 1.036, 95% CI: 1.011–1.062, P=0.005).

Serum HCY levels did not independently predict in-hospital or long-term outcomes in patients with STEMI; however, among elderly patients with STEMI, this study revealed a risk profile for late outcomes that incorporated HCY level.

Cardiac rupture (CR) is a major lethal complication of acute myocardial infarction (AMI). However, no valid risk score model was found to predict CR after AMI in previous researches. This study aimed to establish a simple model to assess risk of CR after AMI, which could be easily used in a clinical environment.

This was a retrospective case-control study that included 53 consecutive patients with CR after AMI during a period from January 1, 2010 to December 31, 2017. The controls included 524 patients who were selected randomly from 7932 AMI patients without CR at a 1:10 ratio. Risk factors for CR were identified using univariate analysis and multivariate logistic regression. Risk score model was developed based on multiple regression coefficients. Performance of risk model was evaluated using receiveroperating characteristic (ROC) curves and internal validity was explored using bootstrap analysis.

Among all 7985 AMI patients, 53 (0.67%) had CR (free wall rupture, n=39; ventricular septal rupture, n=14). Hospital mortalities were 92.5% and 4.01% in patients with and without CR (P < 0.001). Independent variables associated with CR included: older age, female gender, higher heart rate at admission, body mass index (BMI) <25 kg/m², lower left ventricular ejection fraction (LVEF) and no primary percutaneous coronary intervention (pPCI) treatment. In ROC analysis, our CR risk assess model demonstrated a very good discriminate power (area under the curve [AUC]= 0.895, 95% confidence interval: 0.845–0.944, optimism-corrected AUC= 0.821, P < 0.001).

This study developed a novel risk score model to help predict CR after AMI, which had high accuracy and was very simple to use.

Depression and anxiety have been correlated with elevated risks for quality-of-life (QOL), adverse outcomes, and medical expenditure in patients with acute coronary syndrome (ACS). However, the relevant data are lacking for Chinese ACS populations, especially regarding different effects of major depression, anxiety, and comorbidity. The objective of this study was to evaluate the dynamic changes of depression and/or anxiety over 12 months and examine the effects of depression, anxiety, and comorbidity on QOL, adverse outcomes, and medical expenditure in Chinese patients with ACS.

For this prospective longitudinal study, a total of 647 patients with ACS were recruited from North China between January 2013 and June 2015. Among them, 531 patients (82.1%) completed 12-month follow-ups. Logistic regression model was utilized for analyzing the association of baseline major depression, anxiety, and comorbidity with 12-month all-cause mortality, cardiovascular events, QOL, and health expenditure.

During a follow-up period of 12 months, 7.3% experienced non-fatal myocardial infarction (MI) and 35.8% cardiac rehospitalization. Baseline comorbidity, rather than major depression/anxiety, strongly predicted poor 12-month QOL as measured by short-form health survey-12 (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.22–2.52, P = 0.003). Regarding 12-month non-fatal MI and cardiac re-hospitalization, baseline anxiety (OR: 2.83, 95% CI: 1.33–5.89, P < 0.01; OR: 4.47, 95% CI: 1.50–13.00, P < 0.01), major depression (OR: 2.58, 95% CI: 1.02–6.15, P < 0.05; OR: 5.22, 95% CI: 1.42–17.57, P < 0.03), and comorbidity (OR: 6.33, 95% CI: 2.96–13.79, P < 0.0001, OR: 14.08, 95% CI: 4.99–41.66, P < 0.0001) were all independent predictors, and comorbidity had the highest predictive value. Number of re-hospitalization stay, admission frequency within 12 months and medical expenditure within 2 months were the highest in patients with ACS with comorbidity.

Major depression and anxiety may predict 12-month non-fatal MI and cardiac re-hospitalization. However, comorbidity has the highest predictive value with greater medical expenditure and worse QOL in Chinese patients with ACS. And depression with comorbid anxiety may be a new target of mood status in patients with ACS.

High on-treatment platelet reactivity (HTPR) has been suggested as a risk factor for patients with ischemic vascular disease. We explored a predictive model of platelet reactivity to clopidogrel and the relationship with clinical outcomes.

A total of 441 patients were included. Platelet reactivity was measured by light transmittance aggregometry after receiving dual antiplatelet therapy. HTPR was defined by the consensus cutoff of maximal platelet aggregation >46% by light transmittance aggregometry. CYP2C19 loss-of-function polymorphisms were identified by DNA microarray analysis. The data were compared by binary logistic regression to find the risk factors. The primary endpoint was major adverse clinical events (MACEs), and patients were followed for a median time of 29 months. Survival curves were constructed with Kaplan-Meier estimates and compared by logrank tests between the patients with HTPR and non-HTPR.

The rate of HTPR was 17.2%. Logistic regression identified the following predictors of HTPR: age, therapy regimen, body mass index, diabetes history, CYP2C19^*2, or CYP2C19^*3 variant. The area under the curve of receiver operating characteristic for the HTPR predictive model was 0.793 (95% confidence interval: 0.738–0.848). Kaplan-Meier analysis showed that patients with HTPR had a higher incidence of MACE than those with non-HTPR (21.1% vs. 9.9%; χ² = 7.572, P = 0.010).

Our results suggest that advanced age, higher body mass index, treatment with regular dual antiplatelet therapy, diabetes, and CYP2C19^*2 or CYP2C19^*3 carriers are significantly associated with HTPR to clopidogrel. The predictive model of HTPR has useful discrimination and good calibration and may predict long-term MACE.

Visual-spatial neglect (VSN) is a neuropsychological syndrome, and right-hemisphere stroke is the most common cause. The pathogenetic mechanism of VSN remains unclear. This study aimed to investigate the behavioral and event-related potential (ERP) changes in patients with or without VSN after right-hemisphere stroke.

Eleven patients with VSN with right-hemisphere stroke (VSN group) and 11 patients with non-VSN with righthemisphere stroke (non-VSN group) were recruited along with one control group of 11 age- and gender-matched healthy participants. The visual-spatial function was evaluated using behavioral tests, and ERP examinations were performed.

The response times in the VSN and non-VSN groups were both prolonged compared with those of normal controls (P < 0.001). In response to either valid or invalid cues in the left side, the accuracy in the VSN group was lower than that in the non-VSN group (P < 0.001), and the accuracy in the non-VSN group was lower than that in controls (P < 0.05). The P1 latency in the VSN group was significantly longer than that in the control group (F[2, 30] = 5.494, P = 0.009), and the N1 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.343, P = 0.022). When responding to right targets, the lefthemisphere P300 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.255, P = 0.025). With either left or right stimuli, the bilateral-hemisphere P300 latencies in the VSN and non-VSN groups were both significantly prolonged (all P < 0.05), while the P300 latency did not differ significantly between the VSN and non-VSN groups (all P > 0.05).

Visual-spatial attention function is impaired after right-hemisphere stroke, and clinicians should be aware of the subclinical VSN. Our findings provide neuroelectrophysiological evidence for the lateralization of VSN.

Colorectal cancer is the third most common cancer worldwide and still lack of effective therapy so far. Petasin, a natural product found in plants of the genus Petasites, has been reported to possess anticancer activity. The present study aimed to investigate the anticolon cancer activity of petasin both in vitro and in vivo. The molecular mechanism of petasin was also further explored.

Caco-2, LoVo, SW-620, and HT-29 cell lines were used to detect the inhibitory effect of petasin on colon cancer proliferation. Cell viability was determined using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was analyzed by flow cytometry. Hoechst 33258 staining was used to visualize morphological changes. Cell migration was assessed using a wound-healing migration assay, and cell invasion was investigated using Transwell chambers. Western blotting assays were employed to evaluate the expression levels of proteins in the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway. Finally, in vivo activity of petasin was evaluated using the SW-620 subcutaneous tumor model established in Balb/c nude mice. Twelve rats were randomly divided into control group and 10 mg/kg petasin group. The tumor volume was calculated every 7 days for 28 days. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to assess the apoptotic effect of petasin. Differences between two groups were assessed by analysis of independent-sample t tests.

Petasin significantly inhibited the proliferation of human colon carcinoma cell lines, induced apoptosis, and suppressed migration and invasion in SW-620 cells. Western blotting results showed that petasin decreased the phosphorylation of Akt (1.01 ± 0.16 vs. 0.74 ± 0.06, P = 0.042), mTOR (0.71 ± 0.12 vs. 0.32 ± 0.11, P = 0.013), and P70S6K (1.23 ± 0.21 vs. 0.85 ± 0.14, P = 0.008), elevated the expression of caspase-3 (0.41 ± 0.09 vs. 0.74 ± 0.12, P = 0.018) and caspase-9 (1.10 ± 0.27 vs. 1.98 ± 0.22, P = 0.009), decreased the Bcl-2 protein (2.75 ± 0.47 vs. 1.51 ± 0.36, P = 0.008), downregulated the expression of matrix metalloproteinase (MMP)-3 (1.51 ± 0.31 vs. 0.82 ± 0.11, P = 0.021) and MMP-9 (1.56 ± 0.32 vs. 0.94 ± 0.15, P = 0.039) in SW-620 cell. In vivo, 10 mg/kg petasin inhibited tumor growth in Balb/c nude mice (924.18 ± 101.23 vs. 577.67 ± 75.12 mm³ at day 28, P = 0.001) and induced apoptosis (3.6 ± 0.7% vs. 36.0 ± 4.9%, P = 0.001) in tumor tissues.

Petasin inhibits the proliferation of colon cancer SW-620 cells via inactivating the Akt/mTOR pathway. Our findings suggest petasin as a potential candidate for colon cancer therapy.

Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits.

Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n=7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test.

Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = –2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = –2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = –2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = –2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049).

In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.

Portosystemic shunts, including surgical portosystemic shunts and transjugular intra-hepatic portosystemic shunt (TIPS), may have benefit over endoscopic therapy (ET) for treatment of variceal bleeding in patients with cirrhotic portal hypertension; however, whether there being a survival benefit among them remains unclear. This study was to compare the effect of three above-mentioned therapies on the short-term and long-term survival in patient with cirrhosis.

Using the terms "variceal hemorrhage or variceal bleeding or variceal re-bleeding" OR "esophageal and gastric varices" OR "portal hypertension" and "liver cirrhosis," the Cochrane Central Register of Controlled Trials, PubMed, Embase, and the references of identified trials were searched for human randomized controlled trials (RCTs) published in any language with full texts or abstracts (last search June 2017). Risk ratio (RR) estimates with 95% confidence interval (CI) were calculated using random effects model by Review Manager. The quality of the included studies was evaluated using the Cochrane Collaboration’s tool for the assessment of the risk of bias.

Twenty-six publications comprising 28 RCTs were included in this analysis. These studies included a total of 2845 patients: 496 (4 RCTs) underwent either surgical portosystemic shunts or TIPS, 1244 (9 RCTs) underwent either surgical portosystemic shunts or ET, and 1105 (15 RCTs) underwent either TIPS or ET. There was no significant difference in overall mortality and 30-day or 6-week survival among three interventions. Compared with TIPS and ET, separately, surgical portosystemic shunts were both associated with a lower bleeding-related mortality (RR = 0.07, 95% CI = 0.01–0.32; P < 0.001; RR = 0.17, 95% CI = 0.06–0.51, P < 0.005) and rate of variceal re-bleeding (RR = 0.23, 95% CI = 0.10–0.51, P < 0.001; RR = 0.10, 95% CI = 0.04–0.24, P < 0.001), without a significant difference in the rate of postoperative hepatic encephalopathy (RR = 0.52, 95% CI = 0.25–1.00, P = 0.14; RR = 1.09, 95% CI = 0.59–2.01, P = 0.78). TIPS showed a trend toward lower variceal re-bleeding (RR = 0.46, 95% CI = 0.36–0.58, P < 0.001), but a higher incidence of hepatic encephalopathy than ET (RR = 1.78, 95% CI = 1.34–2.36, P < 0.001).

The overall analysis revealed that there seem to be no short-term and long-term survival advantage, but surgical portosystemic shunts are with the lowest bleeding-related mortality among the three therapies. Surgical portosystemic shunts may be the most effective without an increased risk of hepatic encephalopathy and TIPS is superior to ET but at the cost of a higher incidence of hepatic encephalopathy. However, some of findings should be interpreted with caution due to the lower level of evidence and the existence of significant heterogeneity.

When patients attend with medical complaints such as abnormal leucorrhea, the clinician should consider the possibility of an infection in the lower genital tract, such as vulvovaginal candidiasis (VVC). At that point, it is appropriate to then further assess the typical clinical manifestation, diagnosis, and routine management of the infection. However, sometimes, it is not possible to detect any pathogen at all through standard diagnostic techniques. In such a scenario, what happens to these patients?

To the Editor:Overactive bladder (OAB) is a common clinical manifestation of voiding dysfunction. The incidence of OAB among people over 18 years old is 5.9%, and is known to increase with age up to an incidence of 11.3% in people over 40 years old in China. OAB seriously affects the quality of life, causing great inconvenience to patients’ work and home life that can result in a variety of physiologic, psychologic, and social problems. The diagnosis of OAB depends mainly on the patient’s subjective clinical symptoms, as well as auxiliary examination including invasive urodynamic examination, a urination diary, and a symptom questionnaire, which can lack objectivity and accuracy. Thus, in recent years, there has been interest in identifying biomarkers of OAB. Potential biomarkers of OAB identified to date include the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF).

To the Editor: Endometriosis refers to the endometrial tissue (interstitial substance and gland) with growth function occurring in the uterine lining of uterine cavity and the places outside myometrium. It often leads to pain, infertility, nodules or masses and other symptoms and signs, and thus, brings a heavy burden on individuals and society. Traditional blood reflux theory, immune theory, inflammatory theory, hormone theory, etc., cannot fully elucidate the pathogenesis of endometriosis. Recent studies have shown that there is some specificity in eutopic endometria of patients with endometriosis themselves, making it possible that endometrial fragments adhere, invade, and grow outside of the uterine cavity.^[1,2]Eutopic endometria may be one of the key factors in the occurrence of endometriosis. This study intends to use the whole exome sequencing (WES) and gene chip sequencing technology to explore the role of eutopic endometria of patients with ovarian endometriosis (OEM) in the pathogenesis of endometriosis.

To the Editor:Inflammatory myofibroblastoma (IMT) is a rare type of intermediate tumor with malignant potential that often affects children and young adults. Although IMT can arise from various organs, most originate in the lungs, abdomen/pelvis or retroperitoneum. These tumors are thought to arise via a benign inflammatory process, although some exhibit malignant behavior or undergo a malignant transformation. There are no uniform guidelines for the clinical management of IMT.^[1,2]Currently, surgery is first choice of treatment, although other therapeutic options may be considered when total excision is not possible.^[2,3]In this report, we summarize the clinical data of 16 patients aged ≤18 years who were diagnosed pathologically with IMT at our department between 2013 and 2018, review the literature and share our experiences with the diagnosis and treatment of this disease.

To the Editor:Osteoarthritis (OA) is defined as a kind of chronic degenerative joint disorder, and it is generally accepted that genetic factors play an important role in the pathogenesis of OA.

To the Editor:A 66-year-old woman presented with a severe cough and was admitted into hospital in April 2014. Positron emission tomography/computed tomography (PET/CT) scan showed a 2.0 cm×2.0 cm node located on the lower lobe of left lung, multi-mediastinal lymph nodes enlargement and pleural effusion [Figure 1A]. She was also found multi-brain lesions on PET scan. Pleural core needle biopsy was performed, and lung adenocarcinoma was confirmed by pathologists. Direct genetic sequencing was performed with tumor tissue and epidermal growth factor receptor (EGFR) exon 19 deletion was found. Icotinib (Betta, China), a first-generation EGFR tyrosine kinase inhibitor (EGFR TKI), at a dose of 125 mg orally, three times a day was administered. She also received intensity-modulated radiation therapy (IMRT) on brain metastatic tumors with a dose of 56GY/28f. The patient got a partial response (PR) according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). After 30 months remission, disease progressed and the left lung tumor was enlarged [Figure 1B]. Re-biopsy was performed from left lung lesion, the EGFR gene panel was examined, by Amplification Refractory Mutation System polymerase chain reaction (ARMS PCR), EGFR 19 del and EGFR T790 M mutations were detected. Osimertinib was initiated and the patient achieved a PR after 3 months of treatment [Figure 1C]. Nine months later, lung tumor progressed slowly [Figure 1D]. Next-generation sequencing (NGS) was done with new biopsied lung tissue, EGFR 19 del, T790 M, C797G, and V834L mutations were found; and the mutant allele fractions (MAFs) were 85.5%, 61.5%, 36.6%, and 91.1%, respectively. EGFR T790 M and C797G were located incis. Third-line treatment with icotinib and osimertinib in combination was administered. There was no diarrhea, rash, pneumonitis, or transaminitis happened. A stable disease was achieved on CT scan after 2 months of the treatment [Figure 1E]. However, the patient suffered severe back pain after 4 months of the combined treatment. Magnetic resonance imaging showed multiple vertebral metastases. NGS was done with patient’s blood; the results indicated EGFR19 del/T790 M/C797G/V834L mutation and MAF were 0.4%, 0.3%, 0.6%, and 0.8%, respectively. Systemic chemotherapy with carboplatin, pemetrexed plus bevacizumab and currently palliative vertebroplasty then vertebral irradiation were performed. The patient had a stable disease at the last follow-up on April 10, 2018.

To the Editor:Melanocyte stem cells (MSCs), derived from the neural crest, function as the repository of melanocytes (MCs). Currently, most scholars suggest that MSCs mainly exist in the bulge of hair follicles.^[1]At the end of the embryo, the neural crest cells differentiate into melanoblasts (MBs), which migrate through the dermis to the epidermis and into the developing hair follicles.^[2]When the MBs enter the hair follicles, some of them migrate to the hairy mother region and differentiate into mature MCs, producing the pigment and passing it to the keratinocytes (KCs). The others are settled in the follicular and become MSCs, which are responsible for the regeneration of MCs.^[3]The labelled marker of MSCs includes paired box gene 3 (PAX3) and dopachrome tautomerase.^[4]PAX3, as a kind of important transcription factor and belonging to the paired box (PAX) family, plays a key role in the differentiation, migration, and proliferation of MB and MCs.^[5]Some scholars consider thatPAX3plays a key role in maintaining the undifferentiated molecular genetic mechanism of MSCs.^[6]SoPAX3could be used as a marker of MSCs. In addition to MSC, another kind of stem cell called hair follicle stem cell (HFSC) is also found in hair follicles. HFSCs, derived from ectodermal epithelium, have the potential of differentiation in multiple directions; they could accept melanin from mature MCs and generate hair shaft which contains melanin.^[7]HFSCs have various molecular markers, including CK15, CK19, CD34, and others.^[8]As a kind of adhesion molecule, CD34 is selectively expressed on the surface of stem cell of human and other mammalian, and gradually diminishes with the maturity of the cell.^[9]In 2010, some scholars used immunohistochemical staining of CD34 to label hair follicle skin tissue and demonstrated that CD34 had a positive expression with good specificity in the bulge of human hair follicle.^[10]Therefore, in this study, CD34 was used as the marker of HFSCs.

To the Editor:A 70-year-old woman was admitted to the respiratory intensive care unit with severe chest tightness. She had confirmed lung adenosquamous carcinoma 7 months ago. As the epidermal growth factor receptor gene mutations and anaplastic lymphoma kinase fusion gene were negative, she was administered gefitinib for 3 months and then programmed death-1 drugs were treated for two courses. Nearly 1-month of facial ministry edema, computed tomography scan showed that the superior vena cava syndrome appeared. Gamma knife radiosurgery was given 10 times.

To the Editor:Living donor liver transplantation (LDLT) has effectively expanded the donor pool. However, up to 40% of living donors suffer from postoperative complications, which are mostly associated with a right subcostal laparotomy wound.^[1]A pure laparoscopic technique has been employed in living donor right hepatectomy since 2013.^[2,3]In the interest of the donor’s safety, pure laparoscopic living donor right hepatectomy (PLDRH) is recommended for selected donors with normal anatomy. To overcome the hepatic venous variation limitation, we present a case of PLRDH with reconstruction of segment V and VIII tributaries of the middle hepatic vein (MHV) using a cadaveric iliac artery allograft.

To the Editor:The female vagina is a complex microecology system. Generally, the vaginal microbiota of healthy women is dominated by H₂O₂-producingLactobacillus, which decomposes glycogen in vaginal epithelial cells into lactic acid, maintaining the normal acidic environment of the vagina.^[1]And the change of the dominant position of theLactobacilluswill cause a variety of vaginal infections. The conventional treatment of vaginitis mainly through antibiotics to kill the pathogenic microorganisms. Meanwhile,Lactobacillusis sensitive to cephalosporin antibiotics, penicillin, clindamycin, and so on.

To the Editor:Endometrial stromal sarcoma (ESS) is a histologic subtype that accounts for approximately 38% of uterine sarcomas.^[1]Early and complete surgical resection of ESS is the initial treatment.^[2]However, the effect of local treatment modalities for ovarian conservation, lymphadenectomy, and postoperative radiation remains unclear. The International Federation of Gynecology and Obstetrics (FIGO) 2009 system classifies ESS patients with lymph node metastasis as stage IIIC, implying a significant adverse effect of lymph node status on patient prognosis. According to the National Comprehensive Cancer Network,^[3]bilateral salpingo-oophorectomy is preferred in low-grade ESS (LGESS), but no evidence supports the choice of lymphadenectomy, and the management of ovaries may be individualized in patients of reproductive age. Over 80% of patients with LGESS are estrogen receptor-positive,^[4]and postoperative estrogen blockade is recommended for stages II to IV LGESS.^[5,6]Adjuvant radiotherapy is recommended as a postoperative treatment for patients with stage II disease to reduce local recurrence rates. However, the benefits of lymph node resection after primary surgery (total hysterectomy/bilateral salpingooophorectomy) in nonmetastatic LGESS remain controversial.^[7]Moreover, few studies found that oophorectomy and hormone receptor status had no influence on overall survival (OS) and endocrine therapy.^[8]Few studies have also suggested that postoperative pelvic radiotherapy did not improve OS in stage I or stage II uterine sarcomas.^[9]Because these studies are biased by heterogeneity and small sample sizes,^[3]we retrospectively reviewed treatments of patients with LGESS in the surveillance, epidemiology, and end results (SEER) 18 registry database (1973–2015, submission in November 2017) to evaluate the impact of lymphadenectomy, postoperative radiation, and ovarian conservation on survival outcome (5-year OS and 5-year cause-specific survival [CSS]) in LGESS patients.^[10]

In the article titled "Analysis of platelet parameters and activation markers in hematologic metastases of lung cancer" published on pages 735–737, Issue 6, Volume 132 ofChinese Medical Journal,^[1]the affiliation of authors is written incorrectly as "Department of Thoracic Surgery, The 96th Hospital of the People’s Liberation Army of China, Jinan, Shandong 250031, China" instead of "Department of Thoracic Surgery, The 960th Hospital of the People’s Liberation Army of China, Jinan, Shandong 250031, China."