2021年 · 第134卷第06期

Stroke is the leading cause of disability and mortality worldwide. More than half of stroke patients have sleep disorders, including sleep breathing disorders, non-apnea sleep disturbances, and circadian rhythm disruption. Therefore, sleep disturbances, particularly obstructive sleep apnea (OSA), have long been speculated as new preventive and therapeutic targets for stroke. Whether the specific roles of the above sleep disorders in stroke outcome or the efficacy of OSA treatment with continuous positive airway pressure (CPAP) therapy to prevent cerebrovascular events remains uncertain yet. It is noteworthy that there are important limitations among these studies. Here, we briefly reviewed representative studies and subsequently addressed the opportunities mainly for clinical research. The main recommendations are outlined at the end.

The antioxidant effects of bilirubin in Parkinson’s disease (PD) have recently gained much attention from the research community. However, results from these studies have been conflicting. This meta-analysis is conducted to assess the relationship between the serum bilirubin concentration and the risk of PD.

Two reviewers performed a systematic literature search across five databases (MEDLINE, PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials). The case-control studies regarding bilirubin levels in PD patients published up to April 2020 were included. These studies were subjected to rigorous scrutiny and data extraction to determine the standard mean difference (SMD) and the 95% confidence interval (CI), which were analyzed using the Stata V.12.0 statistical software.

A total of eight studies which included 1463 PD cases and 1490 controls were incorporated into our meta-analysis. SMD analysis showed that there was a higher total bilirubin (TBIL) and direct bilirubin (DBIL) levels in PD patients compared with controls (for TBIL, SMD: 0.300, 95% CI: 0.050-0.549, P = 0.018; for DBIL, SMD: 0.395, 95% CI: 0.102-0.688, P = 0.008). However, no significant relationship was found between the serum indirect bilirubin and PD patients (SMD: -0.223, 95% CI: -0.952-0.505, P = 0.548). A subgroup analysis based on ethnicity indicated that the serum TBIL was higher in PD patients of Caucasian descent in contrast to matched healthy controls (SMD: 0.511, 95% CI: 0.324-0.698, P = 0.000, I² = 58.0%).

Higher serum bilirubin levels in PD patients suggest that bilirubin might play a role in the pathogenesis of PD and have the potential to be utilized as a biochemical marker for PD diagnosis and treatment.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by dementia and mental illness. The main pathological changes of AD are the accumulation of amyloid β (Aβ) and phosphorylated tau. With the increase in the aging population, the prevalence among adults aged ≥60 years will be growing from 5.4% (2015) to 6.7% (2050) in China.^[1]At the present stage, the diagnosis of AD is primarily based on the long term clinical observation. Neuro-imaging and invasive cerebrospinal fluid (CSF) measurement of Aβ and tau may help making a differential diagnosis, but the cost to conduct these examinations is high and they are only applicable for the middle to late stages of the disease.^[2]Furthermore, there is still no effective treatment to reverse the clinical symptoms and the pathological changes of AD because most of the patients when they are seen by specialists have already lost the majority of AD-related cortical and hippocampal neurons.^[3]Therefore, the early detection of AD is of importance in order to monitor the AD progression and provide early intervention of the disease. Accordingly, there is a great need to develop low-cost, noninvasive measurement for the early detection of AD. Among many recent research advances, electroencephalography (EEG) has become an effective measurement aiding AD diagnosis and monitoring the disease progression. It has been reported that sleep architecture alteration, decreased θ and δ power could manifest before AD neuropathology.^[4]In this review, we update the recent findings on EEG spectrum analysis, sleep architecture measurement, brain networks research, and their correlation with AD disease progression. We also discuss the potential application of EEG and sleep monitoring in the research of AD pathogenesis, and use them to evaluate the possibility of early AD detection.

Primary progressive aphasia (PPA), which typically refers to a neurodegenerative disease, such as frontotemporal lobar degeneration (FTLD) or Alzheimer disease (AD), is characterized by gradual loss of the brain systems that govern language, with relative sparing of other cognitive domains.^[1]Based on specific speech and language features, clinical consensus criteria published in 2011 for the classification of the PPAs divided them into three subtypes: the semantic variant (svPPA), the non-fluent/agrammatic variant (naPPA), and the logopenic variant (lvPPA) [Supplementary Table 1; http://links.lww.com/CM9/A522]. The naPPA or "progressive non-fluent aphasia", as a form of progressive language disorder that is different from the other subtypes, was first described in 1996 by Grossmanet al.^[2]The major clinical characteristic of naPPA is effortful, non-fluent speech. Patients with naPPA present with agrammatism and/or apraxia of speech (AOS), resulting in articulatory errors and loss of prosody.^[3]

Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients.

Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances.

Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score.

Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.

Several recent genome-wide association studies suggested insomnia and anemia may share some common genetic components. We thus examined whether adults with anemia had higher odds of having insomnia relative to those without anemia in a cross-sectional study and a meta-analysis.

Included in this cross-sectional study were 12,614 Chinese adults who participated in an ongoing cohort, the Kailuan Study. Anemia was defined as hemoglobin levels below 12.0 g/dL in women and 13.0 g/dL in men. Insomnia was assessed using the Chinese version of the Athens Insomnia Scale (AIS). A total AIS score ≥6 was considered insomnia. The association between anemia and insomnia was assessed using a logistic regression model, adjusting for potential confounders such as age, sex, chronic disease status, and plasma C-reactive protein concentrations. A meta-analysis was conducted using the fixed effects model to pool results from our study and three previously published cross-sectional studies on this topic in adult populations.

Individuals with anemia had greater odds of having insomnia (adjusted odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.03-1.70) compared with individuals without anemia. A significant association persisted after we excluded individuals with chronic inflammation, as suggested by C-reactive protein levels >1 mg/L (adjusted OR: 1.68; 95% CI: 1.22-2.32). The meta-analysis results, including 22,134 participants, also identified a positive association between anemia and insomnia (pooled OR: 1.39; 95% CI: 1.22-1.57).

The presence of anemia was significantly associated with a higher likelihood of having insomnia in adults. Due to the nature of the cross-sectional study design, results should be interpreted with caution.

Although a variety of risk factors of pneumonia after clipping or coiling of the aneurysm (post-operative pneumonia [POP]) in patients with aneurysmal subarachnoid hemorrhage (aSAH) have been studied, the predictive model of POP after aSAH has still not been well established. Thus, the aim of this study was to assess the feasibility of using admission neutrophil to lymphocyte ratio (NLR) to predict the occurrence of POP in aSAH patients.

We evaluated 711 aSAH patients who were enrolled in a prospective observational study and collected admission blood cell counts data. We analyzed available demographics and baseline variables for these patients and analyzed the correlation of these factors with POP using Cox regression. After screening out the prognosis-related factors, the predictive value of these factors for POP was further assessed.

POP occurred in 219 patients (30.4%) in this cohort. Patients with POP had significantly higher NLR than those without (14.11 ± 8.90 vs. 8.80 ± 5.82, P < 0.001). Multivariate analysis revealed that NLR remained a significant factor independently associated with POP following aSAH after adjusting for possible confounding factors, including the age, World Federation of Neurosurgical Societies (WFNS) grade, endovascular treatment, and ventilator use. And the predictive value of NLR was significantly increased after WFNS grade was combined with NLR (NLR vs. WFNS grade × NLR, P = 0.011).

Regardless of good or poor WNFS grade, patients having NLR >10 had significantly worse POP survival rate than patients having NLR ≤10. NLR at admission might be helpful as a predictor of POP in aSAH patients.

Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity.

This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson’s disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS).

The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA.

Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

Autophagy of alveolar macrophages is a crucial process in ischemia/reperfusion injury-induced acute lung injury (ALI). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent cells with the potential for repairing injured sites and regulating autophagy. This study was to investigate the influence of BM-MSCs on autophagy of macrophages in the oxygen-glucose deprivation/restoration (OGD/R) microenvironment and to explore the potential mechanism.

We established a co-culture system of macrophages (RAW264.7) with BM-MSCs under OGD/R conditions in vitro. RAW264.7 cells were transfected with recombinant adenovirus (Ad-mCherry-GFP-LC3B) and autophagic status of RAW264.7 cells was observed under a fluorescence microscope. Autophagy-related proteins light chain 3 (LC3)-I, LC3-II, and p62 in RAW264.7 cells were detected by Western blotting. We used microarray expression analysis to identify the differently expressed genes between OGD/R treated macrophages and macrophages co-culture with BM-MSCs. We investigated the gene heme oxygenase-1 (HO-1), which is downstream of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.

The ratio of LC3-II/LC3-I of OGD/R treated RAW264.7 cells was increased (1.27 ± 0.20 vs. 0.44 ± 0.08, t = 6.67, P < 0.05), while the expression of p62 was decreased (0.77 ± 0.04 vs. 0.95 ± 0.10, t = 2.90, P < 0.05), and PI3K (0.40 ± 0.06 vs. 0.63 ± 0.10, t = 3.42, P < 0.05) and p-Akt/Akt ratio was also decreased (0.39 ± 0.02 vs. 0.58 ± 0.03, t = 9.13, P < 0.05). BM-MSCs reduced the LC3-II/LC3-I ratio of OGD/R treated RAW264.7 cells (0.68 ± 0.14 vs. 1.27 ± 0.20, t = 4.12, P < 0.05), up-regulated p62 expression (1.10 ± 0.20 vs. 0.77 ± 0.04, t = 2.80, P < 0.05), and up-regulated PI3K (0.54 ± 0.05 vs. 0.40 ± 0.06, t = 3.11, P < 0.05) and p-Akt/Akt ratios (0.52 ± 0.05 vs. 0.39 ± 0.02, t = 9.13, P < 0.05). A whole-genome microarray assay screened the differentially expressed gene HO-1, which is downstream of the PI3K/Akt signaling pathway, and the alteration of HO-1 mRNA and protein expression was consistent with the data on PI3K/Akt pathway.

Our results suggest the existence of the PI3K/Akt/HO-1 signaling pathway in RAW264.7 cells under OGD/R circumstances in vitro, revealing the mechanism underlying BM-MSC-mediated regulation of autophagy and enriching the understanding of potential therapeutic targets for the treatment of ALI.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore potential molecular targets in ESCC, we quantified the mutation spectrum and explored the relationship between gene mutation and clinicopathological characteristics and programmed death-ligand 1 (PD-L1) expression.

Between 2015 and 2019, 29 surgically resected ESCC tissues and adjacent normal tissues from the Fourth Hospital of Hebei Medical University were subjected to targeted next-generation sequencing. The expression levels of PD-L1 were detected by immunohistochemistry. Mutational signatures were extracted from the mutation count matrix by using non-negative matrix factorization. The relationship between detected genomic alterations and clinicopathological characteristics and PD-L1 expression was estimated by Spearman rank correlation analysis.

The most frequently mutated gene was TP53 (96.6%, 28/29), followed by NOTCH1 (27.6%, 8/29), EP300 (17.2%, 5/29), and KMT2C (17.2%, 5/29). The most frequently copy number amplified and deleted genes were CCND1/FGF3/FGF4/FGF19 (41.4%, 12/29) and CDKN2A/2B (10.3%, 3/29). By quantifying the contribution of the mutational signatures to the mutation spectrum, we found that the contribution of signature 1, signature 2, signature 10, signature 12, signature 13, and signature 17 was relatively high. Further analysis revealed genetic variants associated with cell cycle, chromatin modification, Notch, and Janus kinase-signal transducer and activator of transcription signaling pathways, which may be key pathways in the development and progression of ESCC. Evaluation of PD-L1 expression in samples showed that 13.8% (4/29) of samples had tumor proportion score ≥1%. 17.2% (5/29) of patients had tumor mutation burden (TMB) above 10 mut/Mb. All samples exhibited microsatellite stability. TMB was significantly associated with lymph node metastasis (r = 0.468, P = 0.010), but not significantly associated with PD-L1 expression (r = 0.246, P = 0.198). There was no significant correlation between PD-L1 expression and detected gene mutations (all P > 0.05).

Our research initially constructed gene mutation profile related to surgically resected ESCC in high-incidence areas to explore the mechanism underlying ESCC development and potential therapeutic targets.

Obesity is a fundamental factor in metabolic disorders such as hyperlipidemia, insulin resistance, fatty liver, and atherosclerosis. However, effective preventive measures are still lacking. This study aimed to investigate different surgical protocols for removing partial adipose tissue before the onset of obesity and determine whether, and by which protocol, preliminary adipose removal could exert potent preventive effects against diet-induced metabolic disorders.

Male low-density lipoprotein receptor (LDL-R) knockout (KO) mice were randomly divided into four groups and subjected to epididymal fat removal (Epi-FR) surgery, subcutaneous fat removal (suQ-FR) surgery, both subcutaneous and epididymal fat removal (Epi + suQ-FR) surgery, or sham-operation. After 1 week of recovery, all mice were given a high-fat diet (HFD) for 10 weeks to induce metabolic disorders.

In the Epi-FR group and the sham-operated group, the mean numbers of the residual subcutaneous fat were 28.59 mg/g and 18.56 mg/g, respectively. The expression of relative genes such as Pparg, Cebpa, Dgat2, Fabp4 and Cd36 in the residual subcutaneous fat increased 2.62, 3.90, 3.11, 2.06, 1.78 times in the Epi-FR group compared with that in the sham-operated group. Whereas in the other fat-removal groups, the residual fat depots had no significant change in either size or gene expression, as compared with those of the sham-operated group. Plasma lipid and glucose levels and insulin sensitivity, as detected by the glucose tolerance test, were not significantly alleviated in the three fat removal groups. Liver mass or lipid content was not attenuated in any of the three fat removal groups. The atherosclerosis burdens in the entire inner aorta and aortic root did not decrease in any of the three fat removal groups.

Our data suggest that removal of epididymal adipose or subcutaneous adipose alone or in combination before the onset of obesity did not protect against hyperlipidemia, insulin resistance, fatty liver, or atherosclerosis in LDL-R KO mice fed with a HFD. Hence, adipose removal possibly does not represent a potential approach in preventing obesity-related metabolic disorders in the obesity-susceptible population.

Cognitive impairment is a neurodegenerative change, involving the progression from mild cognitive impairment to dementia.^[1]Sarcopenia is often considered geriatric and is characterized by a progressive and generalized decrease in skeletal muscle mass and strength.^[2]Interestingly, several common pathogenic mechanisms are involved in both sarcopenia and cognitive disorders. The risk factors for sarcopenia include mitochondrial dysfunction, oxidative stress, chronic inflammation, and hormonal changes, all of which are potential causes of cognitive impairment.^[3]Consequently, cognitive impairment may be closely related to sarcopenia. This study aims to examine the relationship between cognitive impairment and sarcopenia among community-dwelling elderly adults.

Meningiomas are common tumors of the central nervous system,^[1,2]and surgery is an effective treatment for meningiomas. Postoperative pneumonia (POP) is one of the common complications after meningioma resection. Even with the improvement of surgical techniques and postoperative care, the incidence of POP has still not been significantly improved. Exploring new predictive indicators can help to screen high-risk POP patients, intervene early, and improve patient prognosis.

Quality of oocytes is closely related to the pregnancy outcome ofin vitrofertilization (IVF). During the process of oocyte maturity, human chorionic gonadotropin (hCG) can simulate the effects of luteinizing hormone peak, which can further accelerate the maturation of follicles. The right time of hCG injection is a decisive factor for retrieving high-quality oocytes.^[1]The optimal hCG injection time is usually determined using average diameter of follicle measured by transvaginal ultrasound. However, the threshold value of the diameter is still controversial.^[2]The diameter measurement becomes increasingly less reliable when there are numerous follicles of different sizes and irregularly shaped structures during controlled ovarian hyperstimulation (COH) cycle. Follicle angiogenesis has been proved to be essential for the oocytes maturity in recent years.^[3]But there are still few quantitative analyses of multi-ultrasound parameters of peri-follicular blood flow (PFBF) and the oocyte quality. This study mainly focuses on the morphology (like threshold of follicle diameter) and PFBF indicators for follicles on the hCG injection day during IVF cycle. The relationships between these indicators and the follicular development and oocyte maturity were systematically analyzed.

During ultrasound-guided regional anesthesia, the operator typically holds the probe in one hand and the needle in the other hand. Meanwhile, another person is frequently needed to control the syringe. However, the availability of a-second-pair-of-hands could be challenging under many circumstances, such as operating room rush hours and off hours. In addition, an assistant, who is unfamiliar with the operator or the procedure, can make a seemingly short procedure a lengthy one, leading to delays or even adverse events due to miscommunication. There have been specialists come up with different solutions to solve this problem.^[1,2,3,4]We developed a technique which allows a single operator to perform ultrasound-guided regional anesthesia.

To the Editor: Motor neuron disease (MND) is a kind of progressive, fatal neurodegenerative disease involving the upper and lower motor neurons and the pyramidal tract. Currently, the etiology of MND remains unknown, and there are limited treatment strategies. Paraneoplastic syndrome (PNS) is a rare form of MND-mimic syndrome. There have been reports of MND-like clinical symptoms in patients with different types of cancer, including breast cancer, lung cancer, and lymphoma. Epidemiological studies have drawn different conclusions, some have suggested that there is no relation between site-specific cancers and the risk of incident amyotrophic lateral sclerosis (ALS), while others have found that the overall risk of cancer of any site is significantly reduced in cases with ALS.^[1]However, the prevalence of tumors in Chinese MND patients and the characteristics of patients with MND concomitant tumors are unclear.

To the Editor:Laparoscopic radical nephrectomy (LRN) is the standard of care for patients with T2 tumors and localized masses not treatable by partial nephrectomy according to the European Association of Urology Guidelines on renal cell carcinoma.^[1]Transperitoneal and retroperitoneal are two main approaches in LRN. With the advantages of easier hilar control, shorter operation time, and less bowel irritation, retroperitoneal approach is preferable in our center. The peritoneal tear is a common intraoperative complication during retroperitoneoscopic procedures, leading to the collapse of the retroperitoneal space. Currently, there is no solid evidence to support the routine closure of peritoneal tears. On the contrary, many surgeons believe that unless subsequent procedures are severely disrupted, peritoneal tears could be left open because they would rapidly be reperitonealized.^[2]According to our daily practice, most peritoneal tears require no repairment. However, a rare case of internal hernia (IH) after retroperitoneal LRN raised our concern about this issue.

To the Editor: Long-term use of antifungals can disrupt the balance of fungal community, making the fungal infection treatments more difficulty and aggravating colitis in patients. The exploration of fecal microbiota transplantation (FMT) in reducingCandidato contain pro-inflammatory immunity induced by gut mycobiota has gained a new appreciation.^[1]The new methodology of FMT was recently coined as washed microbiota transplantation (WMT) based on the automatic purification system and washing process, released by the consensus statement from the Fecal Microbiota-standardization Study Group in 2019.^[2,3]Here, we report a male patient with recurrent fungal infection who was successfully cured by serial WMTs.

To the Editor:The coincidence of Turner syndrome (TS) and Duchenne muscular dystrophy (DMD) is extremely rare, although each is familiar as a sex chromosome aneuploidy and neuromuscular disorders. We report a Chinese girl with TS and DMD with a review of seven cases reported in the literature.

To the Editor:Upper gastrointestinal bleeding (UGIB) is a hemorrhage from mouth to the ligament of Treitz. Climatic condition affects the occurrence of many diseases as the variation on meteorological factors may influence blood pressure^[1]and neuroendocrine factors.^[2]The relationship between UGIB and meteorological factors remains controversial.^[2,3]Such inconsistent conclusions may be related to the study area, etiology of UGIB and time period division. Beijing is a typical temperate monsoon climate with distinct seasons. We retrospectively reviewed patients admitted to our hospital from 2014 to 2018, whose UGIB was caused by peptic ulcer disease (PUD) or esophagogastric varices (EGV). As non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and can cause gastrointestinal injuries, we separated PUD into non-NSAIDs-related ulcer (NSAIDs has never been used or has been discontinued for more than three months) and NSAIDs-related ulcer. Solar term is a special method created in ancient China. This time period division summarizes the influence of meteorological factors. Thus, frequency of UGIB was evaluated based on seasons, months and solar terms [Supplementary Table 1, http://links.lww.com/CM9/A356] in our study. This retrospective study was reviewed and approved by the Medical Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University (No.2018-sci-200).

To the Editor:Community-acquired pneumonia (CAP) is one of the most common infectious diseases, causing high morbidity and mortality. High altitudes are characterized by a hypoxic environment with low barometric pressure, increased ultraviolet radiation, and low humidity. Hypoxia can disturb normal homeostasis of the immune system, especially impairing the function of the T lymphocytes, leading to an increased susceptibility to bacterial infection. The respiratory symptoms of CAP at high altitudes are similar to that of high-altitude pulmonary edema. However, the occurrence of CAP can exacerbate high-altitude pulmonary edema. Few published data of CAP in adults at high altitudes have been reported worldwide. Tibet is located at an average altitude of over 3000 m above sea level, and the clinical and etiological data of CAP at high altitudes are lacking. Almost all the nationwide epidemiological studies of CAP in China have excluded high-altitude regions (>2500 m). Currently, there is no difference between the management strategies of CAP in Tibet and low-altitude regions, with similar CAP guidelines applied in clinical practice.^[1]The special environmental conditions at high altitudes may influence the etiology of CAP; hence, the optimal strategy for the treatment of CAP needs to be investigated in accordance with the local circumstances. Moreover, tuberculosis is prevalent in Tibet with atypical clinical manifestations and is sometimes difficult to distinguish from CAP exclusively based on clinical features without microbiological evaluation. The high prevalence of prior tuberculosis infection further complicates the diagnosis of CAP. We conducted a pilot study of CAP at a single center in Tibet to understand the clinical profile of CAP at high altitudes and optimize the treatment strategy for the management of CAP at high altitudes.

To the Editor: Artificial joint replacement, the most effective treatment for end-stage arthropathy of the hip and knee joint caused by various reasons, has been popularly performed around the world.^[1]It was reported the number of total hip replacement case in the United States in 2017 was 1.1 million and the number of total knee replacement case in 2018 was 1.3 million.^[2]And the case number is increasing annually.

To the Editor:Substrate rigidity and topography are two important biomechanical factors that can modulate the biological behavior of cancer cells such as epithelial to mesenchymal transition (EMT). Currently, although studies have begun to focus on how the mechanical microenvironment determines the fate of multiple cells, the mechanism of the mechanical microenvironment affecting EMT is still unclear.

In the article "Breast cancer immunology and immunotherapy: targeting the programmed cell death protein-1/programmed cell death protein ligand-1" which appeared in vol. 133, issue 7, page 853 ofChinese Medical Journal,^[1]the authors "Jing Zhao^1,2, Jian Huang^2,3" should be corrected as "Jing Zhao¹, Jian Huang²", and their affliations "²Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, Zhejiang 310009, China;³Department of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China" should be corrected as "²Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Department of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China" .