2023年 · 第136卷第02期

Adoptive therapeutic immune cells, such as chimeric antigen receptor (CAR)-T cells and natural killer cells, have established a new generation of precision medicine based on which dramatic breakthroughs have been achieved in intractable lymphoma treatments. Currently, well-explored approaches focus on autologous cells due to their low immunogenicity, but they are highly restricted by the high costs, time consumption of processing, and the insufficiency of primary cells in some patients. Induced pluripotent stem cells (iPSCs) are cell sources that can theoretically produce indefinite well-differentiated immune cells. Based on the above facts, it may be reasonable to combine the iPSC technology and the CAR design to produce a series of highly controllable and economical "live" drugs. Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of "off-the-shelf" strategy to eliminate tumor cells efficiently and safely in a broader range of patients. This review describes the reasonability, feasibility, superiority, and drawbacks of such approaches, summarizes the current practices and relevant research progress, and provides insights into the possible new paths for personalized cell-based therapies.

Tricuspid regurgitation (TR) is an often encountered but undertreated valvular heart lesion. Unlike left-sided valvular diseases, it is estimated that only 5% of patients with significant TR were treated surgically, among which 86% were treated in combination with other major procedures.^[1]This unmet need partially resulted from the lack of prospective evidence on reduced mortality of severe TR benefiting from surgery, alongside a historical viewpoint that functional TR (being the etiology for the vast majority of TR) would be improved once problems in the left heart are corrected. However, untreated severe TR shows various symptoms and a poor prognosis, including increased early and late mortality and impaired quality of life.^[2]With the rapid development of catheter-based valve therapies, less invasive treatment options have been offered to the once forgotten tricuspid valve, further expanding the complexity of decision-making for TR intervention.

Evidence on the relations of the American Heart Association’s ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps.

A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis.

During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed.

ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.

Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender.

Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method.

Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades.

One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.

Colorectal cancer (CRC) screening is effective in reducing CRC incidence and mortality. The aim of this study was to retrospectively determine and compare the detection rate of adenomas, advanced adenomas (AAs) and CRCs, and the number needed to screen (NNS) of individuals in an average-risk Chinese population of different ages and genders.

This was a retrospective study performed at the Institute of Health Management, Chinese People’s Liberation Army General Hospital. Colonoscopy results were analyzed for 53,152 individuals finally enrolled from January 2013 to December 2019. The detection rate of adenomas, AAs, or CRCs was computed and the characteristics between men and women were compared using chi-squared test.

The average age was 48.8 years (standard deviation [SD], 8.5 years) for men and 50.0 years (SD, 9.0 years) for women, and the gender rate was 66.27% (35,226) vs. 33.73% (17,926). The detection rates of adenomas, AAs, serrated adenomas, and CRCs were 14.58% (7750), 3.09% (1641), 1.23% (653), and 0.59% (313), respectively. Men were statistically significantly associated with higher detection rates than women in adenomas (17.20% [6058/35,226], 95% confidence interval [CI] 16.74-17.53% vs. 9.44% [1692/17,926], 95% CI 8.94-9.79%, P < 0.001), AAs (3.72% [1309], 95% CI 3.47-3.87% vs. 1.85% [332], 95% CI 1.61-2.00%, P < 0.001), and serrated adenomas (1.56% [548], 95% CI 1.43-1.69% vs. 0.59% [105], 95% CI 0.47-0.70%, P < 0.001). The detection rate of AAs in individuals aged 45 to 49 years was 3.17% (270/8510, 95% CI 2.80-3.55%) in men and 1.69% (69/4091, 95% CI 1.12-1.86%) in women, and their NNS was 31.55 (95% CI 28.17-35.71) in men and 67.11 (95% CI 53.76-89.29) in women. The NNS for AAs in men aged 45 to 49 years was close to that in women aged 65 to 69 years (29.07 [95% CI 21.05-46.73]).

The detection rates of adenomas, AAs, and serrated adenomas are high in the asymptomatic population undergoing a physical examination and are associated with gender and age. Our findings will provide important references for effective population-based CRC screening strategies in the future.

To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer’s ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution.

This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS).

During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P = 0.025 and P = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01-0.88) and 0.042 (HR: 0.19; 95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups.

Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.

Juvenile amyotrophic lateral sclerosis (JALS) is an uncommon form of amyotrophic lateral sclerosis whose age at onset (AAO) is defined as prior to 25 years. FUS mutations are the most common cause of JALS. SPTLC1 was recently identified as a disease-causative gene for JALS, which has rarely been reported in Asian populations. Little is known regarding the difference in clinical features between JALS patients carrying FUS and SPTLC1 mutations. This study aimed to screen mutations in JALS patients and to compare the clinical features between JALS patients with FUS and SPTLC1 mutations.

Sixteen JALS patients were enrolled, including three newly recruited patients between July 2015 and August 2018 from the Second Affiliated Hospital, Zhejiang University School of Medicine. Mutations were screened by whole-exome sequencing. In addition, clinical features such as AAO, onset site and disease duration were extracted and compared between JALS patients carrying FUS and SPTLC1 mutations through a literature review.

A novel and de novo SPTLC1 mutation (c.58G>A, p.A20T) was identified in a sporadic patient. Among 16 JALS patients, 7/16 carried FUS mutations and 5/16 carried respective SPTLC1, SETX, NEFH, DCTN1, and TARDBP mutations. Compared with FUS mutation patients, those with SPTLC1 mutations had an earlier AAO (7.9 ± 4.6 years vs. 18.1 ± 3.9 years, P < 0.01), much longer disease duration (512.0 [416.7-607.3] months vs. 33.4 [21.6-45.1] months, P < 0.01), and no onset of bulbar.

Our findings expand the genetic and phenotypic spectrum of JALS and help to better understand the genotype-phenotype correlation of JALS.

Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery.

In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC).

A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes (CKMT1B, SMR3B, and OR11M1P) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model.

A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.

Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown.

Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca²⁺-related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance.

Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca²⁺ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments.

Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.

Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization-embryo transfer (IVF-ET) or not. In this study, we compared the outcome of IVF-ET and the development of follicles and embryos between vaccinated and unvaccinated groups.

A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software (http://www.R-project.org/) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio.

The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) (P = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely (P = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) (P= 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) (P= 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes.

In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines show significant effects.

The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum potassium and mortality in dialysis patients of a Chinese nationwide multicenter cohort, taking albumin as a consideration.

This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities.

A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.7 ± 14.8 years, 55.3%(5546/10,027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ± 0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shape was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found (P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation.

Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.

To the Editor: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer death worldwide.^[1]Colorectal adenoma (CRA) is a precursor lesion of CRC. Timely diagnosis and treatment of CRA are important for preventing the occurrence of CRC and improving prognosis. Considering the risks associated with invasive procedures and the high cost of colonoscopy, there is an urgent need to identify reliable non-invasive markers of colorectal neoplasms (CRNs).

To the Editor:Cardiac arrest (CA) is one of the leading causes of adult death globally. According to the latest American Heart Association reports,^[1]the incidences of Emergency Medical Service-assessed adult out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) were 140.7/100,000 and 10.2/1000, respectively.

To the Editor:The aim of early pulmonary rehabilitation (PR) in the intensive care unit (ICU) is to reduce the incidence of post-ICU syndrome, increase the number of ventilator-free days, reestablish and improve functional capacity, improve health-related life quality, promote mental health, and enhance participation in everyday life. PR in the ICU is highly effective and plays an important role in recovery of patients with reduced exercise endurance, functional capacity, and health-related life quality. Several surveys outside China have assessed the implementation of early rehabilitation in the ICU,^[1]but there are few data from China. This study aimed to investigate the awareness and implementation of early PR in secondary- and tertiary-class hospitals with pulmonary and critical care medicine (PCCM) standardized certification. PCCM staff members were recruited to fill out a self-designed questionnaire. We defined early PR as PR within 5 days of ICU admission.

To the Editor: Patients with severe persistent asthma experience greater morbidity with more impairment in quality of life despite higher use of health care resources and being treated with existing asthma treatments such as inhaled corticosteroids and β-agonists, and sometimes oral corticosteroid (OCS) therapy. Type-2 (T2) high asthma has been identified as a phenotype that responds to targeted T2 biologic therapies such as anti-IgE, anti-interleukin (IL) 5, or anti-IL5Rα and anti-IL4Rα monoclonal antibodies, which are currently available in Europe and North America, and are currently introduced in the rest of the world.^[1]Although the prevalence of adult asthma of 4.2% in China is not as high as that in Western countries, severe asthma as defined according to the European Respiratory Society and America Thoracic Society (ERS/ATS) definition is being recognized.^[2]The Chinese Biomarkers for the Prediction of Respiratory Disease Outcomes (C-BIOPRED) cohort of 452 severe asthma patients has characterized these patients that share similar features as those reported in cohorts outside China.^[3]To understand the potential impact of T2-targeted biologic therapies in China, we have determined the prevalence of T2-high asthma based on the criteria of blood eosinophil count (BEC) of either ≥150/μL or ≥300/μL and/or FeNO ≥20 parts per billion (ppb) (https://ginasthma.org/wp-content/uploads/2021/08/SA-Pocket-guide-v3.0-SCREEN-WMS.pdf). Data are presented as mean (standard deviation) or number of subjects (% of total).Pvalues represent comparison across four groups using Kruskal-Wallis tests for continuous variables or Fisher exact tests for categorical variables.P< 0.05 was considered to be statistically significant. T2-high was present ranging from 55.8% (BEC ≥300 μL) to 75.7% (FeNO ≥20 ppb) of the severe asthma patients, while a combination of BEC ≥150/μL and FeNO ≥20 ppb or BEC ≥300/μL and FeNO ≥20 ppb identified 55.9% and 38.7%, respectively [Supplementary Figure 1, http://links. lww.com/CM9/B402]. In 246 severe asthma patients who were re-assessed at one year, a similar percentage of patients remained T2-high, but 10% to 15% in T2-high or T2-low changed to the alternate class. Sputum eosinophil count (SEC) is a better marker of T2-high asthma,^[4]and using a SEC ≥2%,^[5]75% of patients were classified as T2-high.

To the Editor:Non-alcoholic fatty liver disease (NAFLD) becomes a worldwide epidemic with a currently estimated prevalence of 24%. The spectrum of NAFLD includes simple steatosis and non-alcoholic steatohepatitis. Folate, also called vitamin B₉, is the generic term given to a family of compounds, including unsubstituted tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), 5-formylte-trahydrofolate (5-FTHF), 5,10-methylene-THF (5,10-CH₂-THF), and unmetabolized folic acid (UMFA). Folic acid is usually added to products as a dietary supplement. Folate plays a critical role in one-carbon metabolism, which involves the activation and transfer of one carbon unit for biosynthetic processes, including purine and thymidine synthesis and homocysteine remethylation to methionine. NAFLD is closely related to metabolic disorders, whereas the association between folate and NAFLD has not yet been well established. We used data from a nationally representative sample of US adults who were enrolled in the US National Health and Nutrition Examination Survey (NHANES) 2011-2016 to explore the association between folate and NAFLD based on serum and dietary aspects.

To the Editor:Urodynamics is the general term used to describe measurements that assess the function and dysfunction of the lower urinary tract (LUT).^[1]For most LUT disorders, using only an imaging auxiliary examination cannot provide effective clinical evidence of a specific disorder. Hence, some specific approaches are needed to evaluate the function of the bladder and urethra. The pressure-flow study is the most effective method for quantitatively analyzing the storage and voiding functions of the LUT.^[2]

To the Editor:Varicoceles (VCs) refer to the dilation of the veins of the pampiniform plexus. The primary treatment method for VCs with definite surgical indications is the surgical treatment. With the development of minimally invasive technology, the application of microscopic subinguinal varicocelectomy (MSV) has gradually increased in recent years and has become the standard treatment method for VCs.^[1]In the long-term clinical practice of our department, some young people have required surgery for VCs due to physical examination in special industries (e.g., military physical examination). They have wanted the incision to be esthetic, seamless, and concealed. With the expectation of cosmesis, we have made some improvements in the selection of the surgical incision. Using the Scar Cosmesis Assessment and Rating (SCAR) scale,^[2]we comprehensively evaluated the cosmetic effects of patients undergoing improved MSV (IMSV) and MSV in this study.

To the Editor:Mineral supplements are usually regarded as compounds crucial to promoting overall health status and longevity. Systemic mineral status has been demonstrated to be associated with life expectancy in many observational studies, while the causal effects of mineral status on life expectancy have not yet been systematically elucidated. In this study, we investigated the causal effects of six minerals (calcium, magnesium, iron, copper, zinc, and selenium) on life expectancy with large-scale genome-wide association study (GWAS) summary data using two-sample Mendelian randomization (MR) analysis.

To the Editor:Osteoarthritis (OA) is one of the most common age-related diseases and is characterized by synovial inflammation and progressive degradation of cartilage. It was reported that one-third of 65-year-olds and 303 million people globally were affected by OA in 2017.^[1,2]Although there is extensive research published on OA, its pathogenesis remains unclear and controversial. Cartilage degeneration is considered a key pathological factor that leads to disease progression. However, an increasing number of studies have revealed that synovial inflammation may be the main driving force for the development of OA. Wanget al^[3]suggested that synovial inflammation can accelerate cartilage degeneration by activating the toll-like receptors/myeloid differentiation factor 88/nuclear factor-κB (TLRs/MyD88/NF-κB) signaling pathway. Fibroblast-like synoviocytes (FLSs) can acquire an aggressive proliferative phenotype, driving cartilage and bone destruction. Regardless of which driving factor plays a leading role in OA, communication between FLSs and chondrocytes plays a crucial role. Exosomes (EXs) are vesicles with a diameter of approximately 50 to 150 nm and a lipid bilayer membrane structure.^[4]EXs contain many biologically active substances such as non-coding RNAs (ncRNAs), proteins, and messenger RNAs (mRNAs), which play important roles in the cross-talk of OA cells and the intra-articular microenvironment. MicroRNAs (miRNAs) are a group of small ncRNAs approximately 22 nucleotides in length that play key roles in the epigenetics of human diseases by regulating gene expression at the post-transcriptional level. However, few studies have examined differentially expressed miRNAs (DEMs) in synovial fluid (SF)-derived EXs.

To the Editor: Recently, we reviewed almost all the articles reporting surfeit locus containing the six sequence-unrelated housekeeping genes Surfeit 1 to Surfeit 6 since 1988 and one of the family members, surfeit 4 (SURF 4) gene interested us. In this article, we will summarize the characteristics and protein localization ofSURF4gene, as well as its possible physiological functions and pathogenesis in various diseases and cancers, expecting to explore its clinical application values.