2021年 · 第134卷第22期

Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression.

The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science.

Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article.

We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient.

Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with β-blockers, diuretics, and nitrates.

Intravenous thrombolysis (IVT) is an effective way for treating acute ischemic stroke (AIS). However, its effects have not been established among AIS patients with unclear stroke symptoms or with stroke onset for >4.5 h.

We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Google Scholar databases for randomized controlled trials that compared IVT (IVT group) and placebo or usual care (control group [CG]) in AIS patients with disease onset for >4.5 h. The outcomes of interest included the favorable functional outcome (defined as modified Rankin Scale [mRS] scores 0-1) at 90 days, the functional independence (defined as mRS scores 0-2) at 90 days, proportion of patients with symptomatic intracerebral hemorrhage (sICH) and death at 90 days. We assessed the risk of bias using the Cochrane tool. Pre-specified subgroup analyses were performed by age (≤70 years or >70 years), National Institute of Health Stroke Scale (NIHSS, ≤10 or >10) and time window (4.5-9.0 h or >9.0 h).

Four trials involving 848 patients were eligible. The risk of bias of included trials was low. Patients in the IVT group were more likely to achieve favorable functional outcomes (45.8% vs. 36.7%; OR 1.48, 95% CI 1.12-1.96) and functional independence (63.8% vs. 55.7%; OR 1.43, 95% CI 1.08-1.90) at 90 days, but had higher risk of sICH (3.0% vs. 0.5%; OR 5.28, 95% CI 1.35-20.68) at 90 days than those in the CG. No significant difference in death at 90 days was found between the two groups (7.0% vs. 4.1%; OR 1.80; 95% CI 0.97-3.34).

Use of IVT in patients with extended time window may improve their functional outcomes at 90 days, although IVT may induce increased risk of sICH. Care of these patients should well balance the potential benefits and harms of IVT.

Injection sclerotherapy is most effective for internal hemorrhoids, especially for patients with bleeding. However, traditional sclerotherapy via anoscope may cause iatrogenic risk and complications due to misplaced injections.^[1]The flexible endoscopic sclerotherapy for internal hemorrhoids using a short needle without cap assistant was first reported in 1991 in the United States.^[2]The flexible endoscopic injection using a short needle with cap assistant was reported in 2014 in Japan.^[3]Cap-assisted endoscopic sclerotherapy (CAES) primarily using a long needle was reported in 2015^[4]as an emerging flexible endoscopic therapy, and has been widely used for internal hemorrhoids and some prolapse in China. A panel of experts aimed to develop expert recommendations for CAES and derived guidelines on the key issues in hemorrhoidal disease, including rationale, new positioning methods for anus, indications, contraindications, techniques, post-procedure management, and core outcome set for evaluation [Figure 1].

The past decade has witnessed an ever-increasing momentum of transcatheter aortic valve replacement (TAVR) and a subsequent paradigm shift in the contemporary management of severe aortic stenosis (AS). We conducted a multi-centric TAVR registry based on Chinese patients (the China Aortic valve tRanscatheter Replacement registrY [CARRY]) to delineate the clinical characteristics and outcomes of Chinese patients who underwent TAVR and compare the results between different valve types in different Chinese regions.

CARRY is an all-comer registry of aortic valve disease patients undergoing TAVR across China and was designed as an observational study that retrospectively included all TAVR patients at each participating site. Seven hospitals in China participated in the CARRY, and 1204 patients from April 2012 to November 2020 were included. Categorical variables were compared using the chi-squared test, and continuous variables were analyzed using a t test or analysis of variance (ANOVA) test. The Kaplan-Meier curve was used to estimate the risk of adverse events during follow-up.

The mean age of the patients was 73.8 ± 6.5 years and 57.2% were male. The median Society of Thoracic Surgeon-Predicted Risk of Mortality score was 6.0 (3.7-8.9). Regarding the aortic valve, the proportion of bicuspid aortic valve (BAV) was 48.5%. During the hospital stay, the stroke rate was 0.7%, and the incidence of high-degree atrioventricular block indicating permanent pacemaker implantation was 11.0%. The in-hospital all-cause mortality rate was 2.2%. After 1 year, the overall mortality rate was 4.5%. Compared to patients with tricuspid aortic valve (TAV), those with BAV had similar in-hospital complication rates, but a lower incidence of in-hospital mortality (1.4% vs. 3.3%) and 1 year mortality (2.3% vs. 5.8%).

TAVR candidates in China were younger, higher proportion of BAV, and had lower rates of post-procedural complications and mortality than other international all-comer registries. Given the use of early generation valves in the majority of the population, patients with BAV had similar rates of complications, but lower mortality than those with TAV. These findings further propel the extension of TAVR in low-risk patients.

https://www.chictr.org.cn/(No. ChiCTR2000038526).

Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD).

One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran-Mantel-Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups.

At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [-4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P < 0.05 vs. baseline). In the trial group, there was no significant difference in the serum nickel level before vs. after device implantation (P > 0.05).

The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.

Breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM) but without distant metastasis are considered to have a poor prognosis. This study aimed to develop a nomogram to predict the overall survival (OS) of breast cancer patients with ISLNM but without distant metastasis.

Medical records of breast cancer patients who received surgical treatment at the Affiliated Cancer Hospital of Zhengzhou University, Jiyuan People’s Hospital and Huaxian People’s Hospital between December 21, 2012 and June 30, 2020 were reviewed retrospectively. Overall, 345 patients with pathologically confirmed ISLNM and without evidence of distant metastasis were identified. They were further randomized 2:1 and divided into training (n = 231) and validation (n = 114) cohorts. A nomogram to predict the probability of OS was constructed based on clinicopathologic variables identified by the univariable and multivariable analyses. The predictive accuracy and discriminative ability were measured by calibration plots, concordance index (C-index), and risk group stratification.

Univariable analysis showed that estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-positive (HER2+) with Herceptin treatment, and a low axillary lymph node ratio (ALNR) were prognostic factors for better OS. PR+, HER2+ with Herceptin treatment, and a low ALNR remained independent prognostic factors for better OS on multivariable analysis. These variables were incorporated into a nomogram to predict the 1-, 3-, and 5-year OS of breast cancer patients with ISLNM. The C-indexes of the nomogram were 0.737 (95% confidence interval [CI]: 0.660-0.813) and 0.759 (95% CI: 0.636-0.881) for the training and the validation cohorts, respectively. The calibration plots presented excellent agreement between the nomogram prediction and actual observation for 3 and 5 years, but not 1 year, OS in both the cohorts. The nomogram was also able to stratify patients into different risk groups.

In this study, we established and validated a novel nomogram for predicting survival of patients with ISLNM. This nomogram may, to some extent, allow clinicians to more accurately estimate prognosis and to make personalized therapeutic decisions for individual patients with ISLNM.

There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients.

A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients.

After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy.

Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.

Histological and functional recovery after peripheral nerve injury (PNI) is of significant clinical value as delayed surgical repair and longer distances to innervate terminal organs may account for poor outcomes. Low-intensity extracorporeal shock wave therapy (LiESWT) has already been proven to be beneficial for injured tissue recovery on various pathological conditions. The objective of this study was to explore the potential effect and mechanism of LiESWT on PNI recovery.

In this project, we explored LiESWT’s role using an animal model of sciatic nerve injury (SNI). Shockwave was delivered to the region of the SNI site with a special probe at 3 Hz, 500 shocks each time, and 3 times a week for 3 weeks. Rat Schwann cells (SCs) and rat perineurial fibroblasts (PNFs) cells, the two main compositional cell types in peripheral nerve tissue, were cultured in vitro, and LiESWT was applied through the cultured dish to the adherent cells. Tissues and cell cultures were harvested at corresponding time points for a reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence staining. Multiple groups were compared by using one-way analysis of variance followed by the Tukey-Kramer test for post hoc comparisons.

LiESWT treatment promoted the functional recovery of lower extremities with SNI. More nerve fibers and myelin sheath were found after LiESWT treatment associated with local upregulation of mechanical sensitive yes-associated protein (YAP)/transcriptional co-activator with a PDZ-binding domain (TAZ) signaling pathway. In vitro results showed that SCs were more sensitive to LiESWT than PNFs. LiESWT promoted SCs activation with more expression of p75 (a SCs dedifferentiation marker) and Ki67 (a SCs proliferation marker). The SCs activation process was dependent on the intact YAP/TAZ signaling pathway as knockdown of TAZ by TAZ small interfering RNA significantly attenuated this process.

The LiESWT mechanical signal perception and YAP/TAZ upregulation in SCs might be one of the underlying mechanisms for SCs activation and injured nerve axon regeneration.

The chaperonin containing t-complex (CCT) proteins play an important role in cell cycle-related protein degradation in yeast and mammals. The role of the chaperonin containing t-complex 4 (CCT4), one subtype of CCT proteins, in the progress of hepatocellular carcinoma (HCC) was not fully elucidated. Here, we aimed to explore the mechanisms of CCT4 in HCC.

In this study, we used the UALCAN platform to analyze the relationship between CCT4 and HCC, and the association of CCT4 with the overall survival (OS) of HCC patients was also analyzed. CCT4 expression in HCC tumor tissues and normal tissues was also determined by western blot (WB) assay. Lentivirus vector was used to knock down the CCT4 expression, and quantitative polymerase chain reaction and WB were used to determine the level of CCT4 in HCC cell lines. Cell counting kit-8 (CCK-8) and 5-ethynyl-2^＇-deoxyuridine (EdU) assays were used to detect the cell proliferation, and flow cytometry (FCM) was performed to evaluate the effect of CCT4 on the apoptosis of HCC cells. Co-immunoprecipitation (co-IP) assay and WB were used to explore the mechanisms of CCT4 regulating the growth of HCC. Data were calculated from at least three replicate experiments and expressed as mean ± standard deviation. Student’s t test, paired t test, and Kaplan-Meier analysis were used to compare across different groups.

We found CCT4 was upregulated in HCC tissues compared with normal tissues, and its high expression was associated with poor prognosis (P < 0.001). CCT4 was significantly increased in HCC tumor tissues compared with normal tissues (0.98 ± 0.12 vs. 0.23 ± 0.05, t = 7.73, P < 0.001). After being transfected with CCT4 short-hairpin RNA (shRNA), CCT4 was decreased in mRNA level and protein level in both Huh7 (mRNA level: 0.41 ± 0.07 vs. 1.01 ± 0.11, t = 8.09, P = 0.001; protein level: 0.61 ± 0.03 vs. 0.93 ± 0.07, t = 7.19, P = 0.002) and Hep3b cells (mRNA level: 0.55 ± 0.11 vs. 1.04 ± 0.15, t = 4.51, P = 0.011; protein level: 0.64 ± 0.10 vs. 0.95 ± 0.08, t = 4.32, P = 0.012). CCK8 assay indicated that CCT4 knockdown inhibited cell proliferation in both Huh7 (OD value of 3 days: 0.60 ± 0.14 vs. 0.97 ± 0.16, t = 3.13, P = 0.036; OD value of 4 days: 1.03 ± 0.07 vs. 1.50 ± 0.12, t = 5.97, P = 0.004) and Hep3b (OD value of 3 days: 0.69 ± 0.14 vs. 1.10 ± 0.11, t = 3.91, P = 0.017; OD value of 4 days: 1.12 ± 0.12 vs. 1.48 ± 0.13, t = 3.55, P = 0.024) cells. EdU assay showed that CCT4 knockdown inhibited the cell proliferation in both Huh7 (EdU positive rate: [31.25 ± 3.41]% vs. [58.72 ± 3.78]%, t = 9.34, P = 0.001) and Hep3b cells (EdU positive rate: [44.13 ± 7.02]% vs. [61.79 ± 3.96]%, t = 3.79, P = 0.019). FCM assay suggested that CCT4 knockdown induced apoptosis in HCC cells (apoptosis rate of Huh7: [9.10 ± 0.80]% vs. [3.66 ± 0.64]%, t = -9.18, P = 0.001; apoptosis rate of Hep3b: [6.69 ± 0.72]% vs. [4.20 ± 0.86]%, t = -3.84, P = 0.018). We also found that CCT4 could regulate anaphase-promoting complex (APC)^Cdc20 activity via interacting with Cdc20. Furthermore, CCT4 knockdown induced securin (0.65 ± 0.06 vs. 0.44 ± 0.05, t = -4.69, P = 0.009) and B-cell lymphoma-2 (Bcl-2) interacting mediator of cell death (Bim; 0.96 ± 0.06 vs. 0.61 ± 0.09, t = -5.65, P = 0.005) accumulation. The upregulation of securin inhibited cell growth by downregulating cyclin D1 (0.65 ± 0.05 vs. 1.04 ± 0.07, t = 8.12, P = 0.001), and the accumulation of Bim inhibited Bcl-2 (0.77 ± 0.04 vs. 0.87 ± 0.04, t = 3.00, P = 0.040) and activated caspase 9 (caspase 9: 0.77 ± 0.04 vs. 0.84 ± 0.05, t = 1.81, P = 0.145; cleaved caspase 9: 0.64 ± 0.06 vs. 0.16 ± 0.07, t = 1.81, P = 0.001), which led to elevated apoptosis.

Overall, these results showed that CCT4 played an important role in HCC pathogenesis through, at least partly, interacting with Cdc20.

Shenque (CV8) acupoint is located on the navel and has been therapeutically used for more than 2000 years in Traditional Chinese Medicine (TCM). However, clinical research on the underlying therapeutic molecular mechanisms of the CV8 acupoint lags far behind. This study aimed to study the mechanisms of umbilical acupoint therapy by using stem cells.

The morphological characteristics of CV8 acupoint were detected under a stereomicroscope using hematoxylin and eosin (H&E) staining. Oil Red, Masson, and immunohistochemical staining on multi-layered slices were used to identify the type of cells at the CV8 acupoint. Cell proliferation was measured by a cell counting kit-8 (CCK-8) method. Flow cytometry and immunohistochemistry were used for cell identification. Induced differentiation was used to compare the differentiation of cells derived from CV8 acupoint and non-acupoint somatic stem cells into other cell types, such as osteogenic, adipogenic, and neural stem cell-like cells.

Morphological observations showed that adipose tissues at the linea alba of the CV8 acupoint in mice had a mass-like distribution. Immunohistochemical staining confirmed the distribution of stem cell antigen-1 (Sca-1) positive cells in the multi-layered slices of CV8 acupoint tissues. Cells isolated from adipose tissues at the CV8 acupoint exhibited high expression of Sca-1 and CD44 and low expression of CD31 and CD34, and these cells possessed osteogenic, adipogenic, and neurogenic stem cell-like cell differentiation ability. The cell proliferation (day 4: 0.5138 ± 0.0111 vs. 0.4107 ± 0.0180, t = 8.447, P = 0.0011; day 5: 0.6890 ± 0.0070 vs. 0.5520 ± 0.0118, t = 17.310, P < 0.0001; day 6: 0.7320 ± 0.0090 vs. 0.6157 ± 0.0123, t = 13.190, P = 0.0002; and day 7: 0.7550 ± 0.0050 vs. 0.6313 ± 0.0051, t = 42.560, P < 0.0001), adipogenic ([9.224 ± 0.345]% vs. [3.933 ± 1.800]%, t = 5.000, P = 0.0075), and neurogenic stem cell-like cell differentiation (diameter < 50 μm: 7.2000 ± 1.3040 vs. 2.6000 ± 0.5477, t = 7.273, P < 0.0001; diameter 50-100 μm: 2.6000 ± 0.5477 vs. 1.0000 ± 0.7071, t = 4.000, P = 0.0039; and diameter >100 μm: 2.6000 ± 0.5477 vs. 0.8000 ± 0.8367, t = 4.025, P = 0.0038) were significantly enhanced in somatic stem cells derived from the CV8 acupoint compared to somatic stem cells from the groin non-acupoint. However, cells possessed significantly weaker osteogenicity ([2.697 ± 0.627]% vs. [7.254 ± 0.958]%, t = 6.893, P = 0.0023) in the CV8 acupoint group.

Our study showed that CV8 acupoint was rich with adipose tissues that contained abundant somatic stem cells. The biological examination of somatic stem cells derived from the CV8 acupoint provided novel insights for future research on the mechanisms of umbilical therapy.

With accumulating evidence of transcatheter aortic valve replacement (TAVR) worldwide, it is gradually realized that patients being treated are different across different countries, including but not limited to their age, habitus, disease etiology, aortic valve morphology, and sizes of structures.^[1]In China, the average age of TAVR patients is around 5 years younger than industrialized countries,^[2]making Chinese patients a good predictive sample of what the industrialized countries might see in TAVR screening in the near future due to the expansion of this technique to younger patients, but anatomical features appreciated from multi-slice computed tomography (MSCT) in the Chinese patient population have not been well demonstrated.

Transposition of the great arteries (TGA) is a serious and complicated congenital heart disease, accounting for 5% to 7% of all congenital heart malformations. Most fetuses with TGA can survive stably to delivery. After birth, their survival depends on the associated ventricular septal defect (VSD), atrial septal defect (ASD) or patent ductus arteriosus (PDA). Without treatment, approximately 30% of these infants die in the first week after birth and 90% die within the first year.^[1]Arterial switch operation is now recognized worldwide as an effective treatment for TGA and good results have been achieved with this approach. ASO was performed late at our center, with a few patients and high mortality rates in the early stage. In recent years, both the number of patients and the survival rate have increased with the gradual improvement of the skills of the surgical team. More patients have been diagnosed prenatally with the development and promotion of fetal echocardiography. From pregnancy to delivery to surgery, children with TGA require monitoring with close cooperation among medical staff from multiple disciplines. In this study, the data of 87 patients who underwent ASO from January 2014 to December 2019 at our center were retrospectively summarized to analyze the major nonsurgical factors affecting patient prognosis [Table 1]. The study was approved by the Ethics Committee of Shandong Provincial Hospital.

Cardiac resynchronization therapy (CRT) via biventricular pacing (BVP) is known to improve clinical outcomes and decreases all-cause mortality, particularly in patients with left bundle branch block (LBBB) and reduced left ventricular (LV) function.^[1]Recently, several groups have shown the feasibility of left bundle branch area pacing (LBBAP) as an alternative choice to His bundle pacing in patients with LBBB by pacing the left bundle branch (LBB) region beyond the block site with a stable threshold and a short QRS duration (QRSd).^[2,3]However, it is unknown whether the clinical efficacy of LBBAP with an appropriate atrioventricular (AV) delay would be the same as or better than that of LV epicardial pacing or CRT.

To the Editor: Ventricular septal defect (VSD), as the most common congenital heart defect, accounts for up to 40% of all congenital cardiac malformations.^[1]Traditional surgical repair on cardiopulmonary bypass produces substantial trauma and has a long recovery time, and percutaneous device closure is not suitable for all types of VSDs. As minimally invasive procedures have become more common in cardiac surgery, minimally invasive occluder device closure of VSDs under transesophageal echocardiography (TEE) guidance is widely used with excellent preliminary, midterm, and long-term results.^[2,3,4]A small subxiphoid incision and the third/fourth left intercostal space beside the sternum are the two major incisions for device closure of VSDs. However, the differences between the two incisions are unknown. This report describes our experience with two incisions for device closure of VSDs.

Due to a high degree of heterogeneity, different primary sites of diffuse large B-cell lymphoma (DLBCL) will have different clinical features and prognoses. The Revised European-American Lymphoma (REAL) classification emphasizes that knowledge of the primary site of the process is of high diagnostic value for unusual tumors. Diffuse large B-cell lymphoma primarily located in the retroperitoneum (PRLBCL) has been the subject of occasional reports.^[1,2]The retroperitoneal space is large, embedded in a meshwork of loose connective tissue, allowing both primary and metastatic tumors to grow silently before clinical symptoms appear, therefore tumors in the retroperitoneum are often bulky. It is difficult to distinguish them from retroperitoneal lymphoma, and solid tumors such as gastrointestinal stromal ones and neurofibromas.^[3]This study retrospectively analyzed PRLBCLs in our hospital to better understand this disease and summarize our experience.

To the Editor: Facioscapulohumeral muscular dystrophy type 2 (FSHD2) is an epigenetic myopathy caused by variants in genes encoding chromatin regulators, such asSMCHD1: these variants lead to derepression of the D4Z4-encodedDUX4retrogene in skeletal muscle.^[1]The core phenotype of FSHD is progressive muscle weakness in such body parts as the face, shoulder girdle, and upper limbs. Additionally, FSHD may affect the axial muscles and produce bent spine syndrome. Several studies have reported that FSHD2 is associated with causative variants inSMCHD1,^[1,2]but to the best of our knowledge, no Chinese FSHD2 patient has been reported. In this report, we presented a Chinese FSHD2 family with D4Z4 hypomethylation and identified a novel start codon variant (c.1 A>G) inSMCHD1. This study was approved by the Ethics Committee for Medical Research of the First Affiliated Hospital of Fujian Medical University (No. 2016 [17]). Informed consent was obtained from each participant and parent of the participant younger than 18 years of age.

To the Editor: A 58-year-old man, who diagnosed with chronic myelomonocytic leukemia in June 2019, achieved complete bone marrow remission after five courses of chemotherapy (decitabine 35 mg, days 1-5). In December 2019, he underwent an allogeneic hematopoietic stem cell transplant (allo-HSCT) from his human leukocyte antigen-haploidentical daughter. The donor and host pre-transplant Epstein-Barr virus (EBV) serologies were negative. The myeloablative conditioning regimen was administered with cytarabine, busulfan, cyclophosphamide, methyl-N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and anti-thymocyte globulin. The numbers of mononuclear cells and CD34+ cells were 12.23 × 10⁸/kg and 7.57 × 10⁸/kg, respectively. Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A (CSA) and mycophenolate mofetil (MMF). CSA was later changed to tacrolimus due to a gastrointestinal reaction on day +15. The patient had a history of tuberculosis (TB) and received isoniazid and rifapentine for prevention. Neutrophil and platelet engraftment occurred on day +12 and +18, respectively. Cytogenetic studies showed complete donor chimerism on day +26.

To the Editor:Malassezialocated in the skin of patients with atopic dermatitis (AD) might be related to its pathogenesis, consisting ofMalassezia globosaandMalassezia restrictaas the dominant species.^[1]However, the specific molecular mechanisms ofMalasseziaon host immune cells from AD patients are still unclear. In our study, the Affymetrix Human Prime View array was used to detect the effect ofM. globosaon the gene expression of peripheral blood mononuclear cells (PBMCs) from AD patients, which was favorable to further understand the role ofMalasseziacolonization in the pathogenesis of AD.

To the Editor:Toxoplasma gondiiis a widespread apicomplexan parasite and can infect virtually all warm-blooded vertebrates.^[1]Between 22% and 84% of the population in both developed and developing countries is chronically infected withT. gondii. Due to the ethical issues of using animal models forin vivoculture, cell culture systems have been used. Production ofT. gondiitachyzoitesin vitrois essential forToxoplasmainvestigations. It is of great significance to explore the culture conditions ofT. gondii in vitrofor the in-depth study of the metabolism mechanisms of eukaryotes.

To the Editor:Renal cell carcinoma (RCC) accounts for approximately 3% of all malignancies in adults.^[1]Locally advanced RCC has a relatively distinct and adverse prognosis with a 5-year cancer specific survival (CSS) rate ranging from 28% to 67% after curative surgery.^[2]It is important to accurately stratify the risk of disease recurrence for locally advanced RCC. Several prognostic models like Stage, Size, Grade, and Necrosis (SSIGN), Leibovich, Cindolo, Yaycioglu, Memorial Sloan Kettering Cancer Center (MSKCC), Kattan, and Karakiewicz have been developed to predict the prognosis of localized RCC and the concordance index (C-index) has been found to range from 0.65 to 0.84.^[3,4]To our knowledge, these models have mainly been developed based on the data from low-risk patients with RCC. In an external prospective cohort comprising patients with intermediate or high-risk RCC, the performances of these models were found to be sharply decreased (C-index range from 0.587 to 0.69).^[4]Thus, in this study, we aimed to develop a more accurate prognostic model for better risk stratification in locally advanced RCC.

To the Editor:Nodular fasciitis (NF) has been described as a rapidly growing benign soft tissue tumor with fibroblastic/myofibroblastic proliferation.^[1]It commonly involves the upper extremities of adults aged 20 to 40 years.^[1]Due to its rapid growth rate, high cellularity, and brisk mitosis, these lesions are easily confused with soft tissue sarcomas in the diagnosis-making process. Recent findings indicated that recurrent gene rearrangement of ubiquitin-specific protease 6 (USP6), located at 17p13.2, favors the clonally proliferative nature of NF.^[1]USP6rearrangements have been discovered in approximately 90% of NF cases and > 65% of NFs harbor myosin heavy chain 9 (MYH9)-USP6fusions with a type I (exon 1-exon 1) or type II (exon 1-exon 2) pattern.^[1,2]Thus,USP6rearrangements have been adopted as a valuable diagnostic biomarker for distinguishing challenging cases from their histologic mimics. NF is frequently seen in adulthood but extremely rare in infants. Here, we evaluated the clinical, pathological, and genetic features of infantile NF to understand the tumorigenesis mechanism underlying this entity.

To the Editor: Optic neuritis (ON) usually ends with one episode, but recurs in 3% to 5% of patients. Among recurrent patients, those that emerge negative from multiple sclerosis or neuromyelitis optica (NMO) workup are diagnosed with chronic relapsing inflammatory optic neuropathy (CRION). This disease group, first named by Kiddet al,^[1]refers to a clinical situation in which inflammatory optic nerve inflammation on both sides occurs repeatedly and worsens when steroids or immunosuppressants are discontinued. Early diagnosis is important in this group because the risk of blindness is significant, and as such, treatment is focused on preserving vision. However, because a significant number of CRION patients suffer from ocular pain, alleviation of pain should not be overlooked.