Volume 133 · Issue 16 · 2020

Surgical left atrial appendage occlusion (SLAAO) may be associated with a lower risk of thromboembolism in patients with atrial fibrillation undergoing cardiac surgery. However, evidence regarding the effectiveness of SLAAO in patients undergoing mechanical heart valve replacement (MHVR) is lacking. Therefore, we aimed to evaluate the association between SLAAO and the cardiovascular outcomes in patients with atrial fibrillation undergoing MHVR.

We retrospectively analyzed data for 497 patients with atrial fibrillation; 27.6% of the patients underwent SLAAO, and the remainder of the patients did not (No-SLAAO group). The primary outcome was a composite of ischemic stroke, systemic embolism, and all-cause mortality. Cumulative event-free survival rates were estimated using Kaplan-Meier curves, and we performed multivariate Cox analyses to evaluate the association between SLAAO and outcomes. We used one-to-one propensity score matching to balance patients’ baseline characteristics, and analyzed 120 matching pairs.

Five patients died within 30 days postoperatively, and there were no significant differences between the two groups regarding in-hospital complications (all P > 0.05). After a median follow-up of 14 months, 14 primary events occurred. Kaplan-Meier curves showed no difference in the cumulative incidence of freedom from the primary outcome (log-rank P = 0.830), hemorrhagic events (log-rank P = 0.870), and the secondary outcome (log-rank P = 0.730), between the two groups. Multivariable Cox proportional hazards regression analysis showed no association between SLAAO and any outcome (all P > 0.05). After propensity score matching, cardiopulmonary bypass time and aortic cross-clamp time, and the postoperative length of stay were significantly longer in the SLAAO group (all P < 0.05); results were similar to the unadjusted analyses.

Concomitant SLAAO and MHVR was associated with longer length of stay, and cardiopulmonary bypass time and aortic cross-clamp time, but was not associated with additional protective effects against thromboembolic events and mortality during the 14-month follow-up.

Total and differential white blood cell counts are important for the diagnostic evaluation of suspected diseases. To facilitate the interpretation of total and differential white blood cell counts in pediatric patients, the present study investigated age-dependent changes in total and differential white blood cell counts in healthy reference children.

Data were obtained from the Pediatric Reference Intervals in China study (PRINCE), which aims to establish and verify pediatric reference intervals for Chinese children based on a nationwide multicenter cross-sectional study from January 2017 to December 2018. Quantile curves were calculated using the generalized additive models for location, shape, and scale method. The 2.5th, 50th, and 97.5th quantile curves were calculated for both total and differential white blood counts. Percents of stacked area charts were used to demonstrate the proportions of differential white blood cells. All statistical analyses were performed using R software.

Both 50th and 97.5th quantiles of total white blood cell count and monocyte count were highest at birth, then rapidly decreased in the first 6 months of life; relatively slow reduction continued until 2 years of age. The lymphocyte count was low during infancy and increased to its highest level at 6 months of age; it then exhibited moderate and continuous reduction until approximately 9 years of age. The pattern of neutrophil count changed with age in a manner opposite to that of lymphocyte count. Besides, there were two inter-sections of lymphocyte count and neutrophil count during infancy and at approximately 5 years of age, based on locally weighted regression (LOESS) analysis. There were no apparent age-related changes in eosinophil or basophil counts.

These data regarding age-related changes in total and differential white blood cell counts can be used to assess the health of pediatric patients and guide clinical decisions.

There is limited evidence of the effects of local anesthesia (LA) on outcomes of non-surgical periodontal treatment (NSPT), in particular among the Chinese. This retrospective cohort study aimed to evaluate the effects of LA on short-term treatment outcomes of NSPT and to determine under what circumstances LA should be prescribed to improve these outcomes.

Data from periodontal examinations of 3980 patients were used. The data were from 3-month re-evaluation records of an electronic periodontal charting record system in the Department of Periodontology of Peking University School and Hospital of Stomatology from June 2008 to January 2015. Descriptive analyses included changes in probing depth (PD) and the Mazza bleeding index (BI). Two-level (patient and tooth) logistic regression models and three-level (patient, tooth, and site) linear regression models were constructed to analyze the influence of LA on PD for all teeth/sites and teeth/sites with an initial PD ≥ 5 mm. Decreases in PD and BI at sites under LA using the initial PD were also compared.

A significantly higher mean decrease in PD after NSPT was found in the LA group than in the no local anesthesia (NLA) group (0.98 vs. 0.54 mm, t = 24.12, P < 0.001). A significantly higher probability of decreases was found in the LA group in BI (percentages of teeth with BI > 1 and BI > 2) for all teeth (16.7% vs. 13.8%, t=3.75, P < 0.001; 34.7% vs. 28.1%, t = 6.73, P < 0.001) and PD for teeth with PD ≥ 5 mm (32.3% vs. 17.3%, t = 28.48, P < 0.001). The difference in PD between the LA and NLA groups increased as the initial PD increased. The difference between the two groups was 0.12 to 0.22 mm for sites with a baseline PD < 7 mm; however, it increased to 0.41 to 1.37 mm for sites with a baseline PD ≥ 7 mm.

LA improved the decrease in PD after NSPT. Root debridement at sites with initial PD ≥ 7 mm should be performed under routine LA.

Due to airway remodeling and emphysematous destruction in the lung, the two classical clinical phenotypes of chronic obstructive pulmonary disease (COPD) are emphysema and bronchiolitis. The present study was designed to investigate the levels of small airway immunoglobulin A (IgA) in COPD with "emphysema phenotype." The study also evaluated the associations between the small airway IgA levels and the severity of disease by the extent of emphysema versus airflow limitation.

Thirty patients (20 with COPD and ten healthy smokers) undergoing lung resection surgery for a solitary peripheral nodule were included. The study was conducted from January 2015 to December 2018 in the Shanxi Dayi Hospital. The presence of small airway IgA expression was determined in the lung by immunohistochemistry. In vivo, Wistar rats were exposed to silica by intratracheal instillation. Rats were sacrificed at 15 and 30 days after exposure of silica (n = 10 for each group). We also evaluated airway IgA from rats.

Small airway secretory IgA (sIgA), dimeric IgA (dIgA), and dIgA/sIgA of Global Initiative for Chronic Obstructive Lung Disease grade 1-2 COPD patients showed no difference compared with smoking control subjects (5.15±1.53 vs. 6.03±0.85; 1.94±0.66 vs. 1.67±0.04; 41.69±21.02 vs. 28.44±9.45, all P > 0.05). dIgA/sIgA level in the lung of COPD patients with emphysema showed higher levels than that of COPD patients without emphysema (51.89±24.81 vs. 31.49±9.28, P=0.03). The percentage of low-attenuation area below 950 Hounsfield units was positively correlated with dIgA/sIgA levels (r=0.45, P=0.047), but not associated with the severity of disease by spirometric measurements (forced expiratory volume in the first second %pred, P>0.05). Likewise, in the rat study, significant differences in sIgA, dIgA, dIgA/sIgA, mean linear intercept, mean alveoli number, and mean airway thickness of bronchioles (VV airway, all P < 0.01) were only observed between control rats and those exposed for 30 days. However, in the group exposed for 15 days, although the VV airway was higher than that in normal rats (27.61±2.26 vs. 20.39±1.99, P<0.01), there were no significant differences in IgA and emphysema parameters between the two groups (all P>0.05).

Airway IgA concentrations in mild and moderate COPD patients are directly associated with the severity of COPD with "emphysema phenotype" preceding severe airway limitation. This finding suggests that small airway IgA might play an important role in the pathophysiology of COPD, especially emphysema phenotype.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. It has been demonstrated that microRNA-145 (miR-145) is correlated with the progression of various cancers by regulating the expression of multiple target genes, especially a number of genes that regulate angiogenesis and proliferation. However, the underlying mechanisms of miR-145 in tumor angiogenesis of UM are still not well illustrated. Thus, we aimed to explore the potential target genes or pathways regulated by miR-145 in UM and the effect of miR-145 on invasion and angiogenesis.

Totally, 24 choroid samples were collected in our study, including 12 UM samples and 12 normal uveal tissues. The expression of neuroblastoma RAS viral oncogene homolog (N-RAS), phosphorylated protein kinase B (p-AKT), and vascular endothelial growth factor (VEGF) in UM tissues and normal uveal tissues was analyzed using Western blotting analysis. Lentivirus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145. Transwell and endothelial cell tube formation assay were used to measure the effects of miR-145 on the invasion and angiogenesis of UM in vitro. The downstream target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase assay. BALB/c nude mice models were established to investigate the mechanisms of miR-145 on tumor growth and angiogenesis in vivo. Group data comparisons were performed using analysis of Student’s t test. A two-tailed P < 0.05 was considered as statistically significant.

The results of Western blotting analysis indicated that the expressions of N-RAS (1.10 ± 0.35 vs. 0.41 ± 0.36, t = 3.997, P = 0.012), p-AKT (1.16 ± 0.22 vs. 0.57 ± 0.03, t = 7.05, P = 0.001), and VEGF (0.97 ± 0.32 vs. 0.45 ± 0.21, t = 3.314, P = 0.008) in UM tumor tissues were significantly higher than those in normal uveal tissue. Luciferase assay demonstrated N-RAS and VEGF as downstream targets of miR-145. Moreover, tube formation assay revealed that miR-145-transfected human microvascular endothelial cell line formed shorter tube length (36.10 ± 1.51 mm vs. 42.91 ± 0.94 mm, t = 6.603, P = 0.003) and less branch points (350.00 ± 19.97 vs. 406.67 ± 17.62, t = 3.685, P = 0.021) as compared with controls. In addition, the numbers of invaded MUM-2B and OCM-1 cells with miR-145 overexpression were significantly lower than the controls (35.7 ± 3.3 vs. 279.1 ± 4.9, t = 273.75, P < 0.001 and 69.5 ± 4.4 vs. 95.6 ± 4.7, t = 21.27, P < 0.001, respectively). In vivo, xenografts expressing miR-145 had smaller sizes (miR-145 vs. miR-scr, 717.41 ± 502.62 mm³vs. 1694.80 ± 904.33 mm³, t = 2.314, P = 0.045) and lower weights (miR-145 vs. miR-scr, 0.74 ± 0.46 g vs. 1.65 ± 0.85 g, t = 2.295, P = 0.045).

Our results indicated that miR-145 is an important tumor suppressor and the inhibitory strategies against N-RAS/VEGF signaling pathway might be potential therapeutic applications for UM in the future.

Pulmonary deportation of hydatidiform mole is an exceedingly rare entity. The underlying mechanisms and proper management strategies remain unclear based on sporadic case reports over the past six decades. This study aimed to investigate the clinical features and rational treatment of patients with benign molar pregnancies with pulmonary deportation based on our experience.

Medical records of 20 cases of hydatidiform mole with pulmonary deportation were retrospectively reviewed at Peking Union Medical College Hospital from November 2006 to May 2019. The detailed information of all patients was recorded and analyzed. Patients were divided into different groups according to their characteristics and Mann-Whitney U test was used to compare the duration to achieve a normal β-human chorionic gonadotrophin (β-hCG) level after the first evacuation among groups.

Initial pulmonary computed tomography scans showed suspected bilateral, left and right chest deportation of hydatidiform mole in 12, four, and four patients, respectively, with the maximum nodular diameter ranging from 0.6 to 1.2 cm. Ten patients achieved lesion resolution while the remaining ten patients achieved decreases in the size of their pulmonary lesions. The median duration to achieve a normal β-hCG level after the first evacuation was 15.5 (13.0, 21.9) weeks. There was no significant difference in the duration to achieve a normal β-hCG level after the first evacuation between two groups based on age (≥40 years vs. < 40 years: 15.8 [12.2, 21.5] weeks vs. 15.5 [12.9, 23.0] weeks, Z = 0.094, P = 0.925), type of antecedent mole (partial mole vs. complete mole: 15.2 [12.5, 27.4] weeks vs. 15.9 [12.9, 21.5] weeks, Z = 0.165, P = 0.869), distribution of pulmonary nodules (bilateral lungs vs. unilateral lung: 15.2 [12.8, 22.5] weeks vs. 15.9 [13.2, 22.2] weeks, Z = 0.386, P = 0.700), maximum size of pulmonary nodules (>0.5 cm vs. ≤0.5 cm: 13.0 [11.3, 17.2] weeks vs. 16.0 [14.5, 23.8] weeks, Z = 1.815, P = 0.070), and number of uterine evacuations (once vs. twice or three times: 15.0 [13.0, 16.3] weeks vs. 16.0 [12.8, 23.9] weeks, Z = 0.832, P = 0.405). The post-molar cohort was followed up for 17 to 139 months, and no gestational trophoblastic neoplasia was observed.

No surgeries other than uterine evacuation and no chemotherapy regimens are recommended for such patients if they achieve satisfactory decreases in the level of hCG and gradual decrease or disappearance of pulmonary deportation nodules. Patients should be informed about the necessity of long-term follow-up. More collaborative international studies on this exceedingly rare condition may guide decisions regarding optimal management strategies.

The casein kinase 2-interacting protein-1 (CKIP-1) is important in the development of osteoblasts and cardiomyocytes. However, the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells (MSCs) remain unclear. This study aimed to determine whether CKIP-1 affects osteogenic differentiation in MSCs and explore the relationship of CKIP-1 and inflammation.

Bone marrow MSCs of CKIP-1 wild type (WT) and knockout (KO) mice were cultivated in vitro. Cell phenotype was analyzed by flow cytometry, colony formation was detected to study the proliferative ability. Osteogenic and adipogenic induction were performed. The osteogenic ability was explored by alizarin red staining, alkaline phosphatase (ALP) staining and ALP activity detection. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to determine the mRNA expression levels of osteoblast marker genes. The adipogenic ability was detected by oil red O staining. Content of the bone was analyzed to observe the differences of bone imaging parameters including trabecular bone volume/tissue volume (BV/TV), bone surface area fraction/trabecular BV, trabecular number (Tb.N), and trabecular spacing (Tb.sp). Interleukin (IL)-1β was injected on WT mice of 2 months old and 18 months old, respectively. Difference in CKIP-1 expression was detected by RT-PCR and western blot. The relationship between CKIP-1 and inflammation was explored by RT-PCR and western blot.

ALP assays, alizarin red staining, and qRT-PCR showed that MSCs derived from CKIP-1 KO mice exhibited a stronger capability for osteogenesis. Micro-computed tomography detection showed that among 18-month-old mice, CKIP-1 KO mice presented significantly higher bone mass compared with WT mice (P = 0.02). No significant difference was observed in 2-month-old mice. In vivo data showed that expression of CKIP-1 was higher in the bone marrow of aging mice than in young mice (4.3-fold increase at the mRNA level, P = 0.04). Finally, the expression levels of CKIP-1 in bone marrow (3.2-fold increase at the mRNA level, P = 0.03) and cultured MSCs were up-regulated on chronic inflammatory stimulation by IL-1β.

CKIP-1 is responsible for negative regulation of MSC osteogenesis with age-dependent effects. Increasing levels of inflammation with aging may be the primary factor responsible for higher expression levels of CKIP-1 but may not necessarily affect MSC aging.

Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice.

Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student’s t test.

Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152).

These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.

Electrical stimulation has been recommended as an effective therapy to prevent muscle atrophy after nerve injury. However, the effect of electrical stimulation on the proliferation of satellite cells in denervated muscles has not yet been fully elucidated. This study was aimed to evaluate the changes in satellite cell proliferation after electrical stimulation in nerve injury and to determine whether these changes are related to the restoration of myofiber cross-section area (CSA).

Sciatic nerve crush injury was performed in 48 male Sprague-Dawley rats. In half (24/48) of the rats, the gastrocnemius was electrically stimulated transcutaneously on a daily basis after injury, while the other half were not stimulated. Another group of 24 male Sprague-Dawley rats were used as sham operation controls without injury or stimulation. The rats were euthanized 2, 4, and 6 weeks later. After 5-bromo-2’-deoxyuridine (BrdU) labeling, the gastrocnemia were harvested for the detection of paired box protein 7 (Pax7), BrdU, myofiber CSA, and myonuclei number per fiber. All data were analyzed using two-way analysis of variance and Bonferroni post-hoc test.

The percentages of Pax7-positive nuclei (10.81 ± 0.56%) and BrdU-positive nuclei (34.29 ± 3.87%) in stimulated muscles were significantly higher compared to those in non-stimulated muscles (2.58 ± 0.33% and 1.30 ± 0.09%, respectively, Bonferroni t = 15.91 and 18.14, P < 0.05). The numbers of myonuclei per fiber (2.19 ± 0.24) and myofiber CSA (1906.86 ± 116.51 μm²) were also increased in the stimulated muscles (Bonferroni t = 3.57 and 2.73, P < 0.05), and both were positively correlated with the Pax7-positive satellite cell content (R² = 0.52 and 0.60, P < 0.01). There was no significant difference in the ratio of myofiber CSA/myonuclei number per fiber among the three groups.

Our results indicate that satellite cell proliferation is promoted by electrical stimulation after nerve injury, which may be correlated with an increase in myonuclei number and myofiber CSA.

Now, a novel coronavirus epidemic has posed a major threat to human health. Medical staff face a high risk of occupational exposure at very early stages of an epidemic. Once the medical staff are infected, it will greatly affect the "fighting capacity" of medical institutions, and help the virus spread within hospitals. These issues strongly suggest the critical role of hospital management, prevention, and control systems in the fight against infectious diseases.

Magnetic surgery is defined as surgical treatment by utilization of magnetic technology, including magnetic devices and carriers. Magnetic techniques include compression, navigation, levitation, anchoring, and delivery.^[1]Interest in magnetic surgery has increased over the past decade due to its potential to facilitate minimally invasive procedures. Thus guidelines for the use of magnetic technology in surgery need to be established.

In December 2019, highly infectious 2019 novel coronavirus disease (COVID-19) broke out in Wuhan, China. The pathogen was identified as 2019 novel coronavirus (2019-nCoV).^[1]The 2019-nCoV had the capacity to cause systematic injury including renal injuries besides pneumonia.^[2]Angiotensin-converting enzyme 2 (ACE2) acts as a cell entry receptor for 2019-nCoV.^[1]ACE2 expression was dominant in proximal tubules within the kidney. In this study, the clinical data from hospitalized patients were retrospectively analyzed at their admission to identify if there is any evidence of proximal tubule injury.

Coronavirus disease 2019 (COVID-19), caused by a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which can lead to pneumonia and severe acute respiratory syndrome, continues to spread across the globe.^[1]Due to strict precautionary measures, the epidemic situation of COVID-19 has been initially controlled in China. However, the numbers of confirmed positive cases of COVID-19 and deaths are increasing in other countries. In fact, the SARS-CoV-2 is more contagious than severe acute respiratory syndrome coronavirus (SARS-CoV)^[2]and Middle East respiratory syndrome coronavirus (MERS-CoV).^[3]Therefore, the rapid and accurate identification of pathogenic viruses plays a vital role in controlling epidemics. Computed tomography imaging and some hematologic parameters are the initial markers for COVID-19 infection,^[4,5]while viral nucleic acid detection by reverse transcription-polymerase chain reaction is used as a gold standard for the clinical diagnosis of suspected cases.^[1]However, nucleic acid detection is time consuming and requires certified laboratories and trained technicians, and the results are easily affected by the quality of the specimens. Detection of serum-specific antibodies using colloidal gold immunochromatography assay (GICA) is another key approach for the rapid and highly sensitive diagnosis of viral infection. More importantly, this method does not require special equipment and reagents and is ideal for point-of-care testing.

Anticoagulants are routinely prescribed in the first several weeks after atrial fibrillation (AF) catheter ablation. Non-vitamin K antagonist oral anticoagulants (NOACs) have been recommended over warfarin for their superiority. Unlike warfarin need regular clinical visit to perform blood test, NOACs are more patient friendly. But the lack of routine medical contact may lead to poor adherence. Strict adherence to anticoagulant treatment is essential for both efficacy and safety. Considering NOACs are increasingly commonly used in China, it is therefore necessary to evaluate the adherence of NOACs after AF catheter ablation. The purpose of this research was to investigate the treatment adherence and identify factors that could improve the quality of anticoagulation.

Pelvic organ prolapse (POP) is a disease that is usually not life-threatening but can seriously affect the life quality of patients. It is currently believed that there is a significant correlation between POP and cervical elongation.^[1]In POP surgery, cervical length has a critical impact on the choice of surgical approach and decision making of uterine conservation. It remains unclear how to evaluate the length of the cervix before surgery. In particular, there is a lack of cervical length data in Chinese women with POP.

SalmonellaAberdeen is a ubiquitous pathogen that can cause severe gastroenteritis and plays an important role in food-borne illness and international food-trade dispute.^[1]However, the molecular biological characteristics of this organism have been rarely studied. This study was conducted in accordance with the Declaration of Helsinki and aimed to assess the epidemiological and clinical characteristics of a food-borne outbreak caused bySalmonellaAberdeen. Furthermore, the molecular biological characteristics of the outbreak isolates were detected and analyzed. From June 10 to 12, 2018, an enteritis outbreak affected 75 employees in the Fushan district of Yantai, Shandong province, China, including 33 males and 42 females. The mean age of the patients was 34.2 ± 5.3 years. An epidemiological investigation revealed that all infected employees had eaten the lunch provided by a catering company on June 9, 2018. In total, 22 samples, including four feces samples, five surplus food samples, eight cooking utensils used by the catering company, and five samples of chicken and eggs from the market where the food raw materials were purchased, were collected.^[2]Of the 22 samples, six (27.2%) were tested positive forSalmonellaAberdeen (O11:Hi;1,2), including three isolates from feces (3/4, 75%) and three from surplus foods (3/5, 60%). Pulsed-field gel electrophoresis (PFGE) results showed the highly close correlation among the isolates, which were digested using the restriction enzyme nucleases XbaI (96.8%) and BlnI (100%) (Takara, Dalian, Liaoning, China) according to the PulseNet standardized PFGE protocol.^[3]The PFGE patterns were analyzed using BioNumerics, Version 6.0 (Applied Maths, Kortrijk, Belgium).

To the Editor:With the development of clinical research and the application of cord blood, the clinical value of umbilical cord blood (UCB) has drawn more and more attention. UCB has been increasingly applied to treatments of hematological diseases, autoimmune diseases, and malignant tumors in children and adults^[1]and has achieved high overall survival.^[1,2,3]UCB contains substantial amounts of various stem cells, including hematopoietic stem cells (HSC), mesenchymal stem cells, endothelial progenitor cells, and so on^[4]; among them, HSC are most widely used in study and clinical application. Transplantation, where UCB HSC are implanted into patients, requires ruining the immune system and hematopoietic system before the procedure. Another therapeutic method is UCB infusion, where UCB is regarded as a nutrient, to improve the outcome of peripheral blood HSC transplantation^[5]or symptoms via paracrine pathway of UCB stem cells.^[6]In addition to the application of allogeneic UCB, autologous UCB has also been used in clinical treatment research. Autologous UCB is not limited to treating hemopathy, but also used to treat non-genetic metabolic disease, immune disease, and nervous system injury.^[6]

To the Editor:A first infection of varicella-zoster virus (VZV) during pregnancy can cause serious systemic disease to both mother and the fetus. Despite this maternal herpes zoster (HZ) does not increase fetal mortality, and the transmission of varicella-zoster virus to the fetus rarely occurs. Although HZ infection has a minimal effect on the fetus, maternal HZ can cause significant complications for the mother.^[1]

To the Editor:This study reported that a case of Philadelphia chromosome-positive B-acute lymphoblastic leukemia (Ph⁺B-ALL) underwent a lineage switch to acute myeloid leukemia (AML) following CD19 chimeric antigen receptor (CAR)-modified T (CAR-T) cells therapy. The study was reviewed and approved by the ethics committee of the first affiliated hospital of Nanjing Medical Universit (No. 2020-QT-06). A 46-year-old woman with a 1-month history of chest pain was admitted to our hospital on January 24, 2014. The results of her laboratory examinations were as follows: (i) White blood cell count 12.01 × 10⁹/L; hemoglobin 92 g/L; platelet count 47 × 10⁹/L; (ii) Bone marrow (BM) smears showed a massive infiltrate (95.2%) of blast cells; (iii) Immunophenotypic analysis by flow cytometry (FCM) revealed that blast cells accounted for 66.3%, which were positive for CD34, CD10, CD19, CD20, CD22, CD38, and human leukocyte antigen DR; (iv) Karyotype analysis showed no mitotic phase; (v) Fluorescencein situhybridization demonstrated a positive Philadelphia chromosome (BCR-ABLfusion gene); (vi) BM quantitative real-time polymerase chain reaction (qRT-PCR) detected a positiveBCR-ABLp190 transcript (BCR-ABL, 184.1%). She was thus diagnosed with Ph⁺B-ALL.

To the Editor:In September of 2016, a 26-year-old farmer from Yunnan Province with no medical or drug history exhibited painless cutaneous nodules on his chest. Later the nodules gradually appeared on his limbs, face, and trunk. After half a month, he had moderate to high-grade fever (39.5°C) and numbness of limbs. He reported no coughing, diarrhea, arthralgia, and myalgia. There was no similar illness in his family. Laboratory tests in a local hospital showed elevated white blood cell and neutrophil count. Serology tests for infection were negative. Anti-neutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase ANCA (MPO-ANCA) were positive. The computed tomography of chest was normal. Based on the clinical and laboratory manifestations, he was diagnosed as ANCA-associated vasculitis (AAV) and was initially treated with intravenous methylprednisolone 80 mg/day and cyclophosphamide (0.4 g/2 weeks) for four times in the local hospital. In the course of the treatment, fever and skin nodules were temporarily relieved, but reoccurred when prednisone tapered to 20 to 30 mg/day. The recurrent fever, skin nodules, and numbness of limbs had lasted for 2 years, and thus, he was referred to the Sichuan University West China Hospital.

To the Editor:A 59-year-old Chinese woman was admitted for fatigue and fever for 1 month. She was diagnosed with chronic active Epstein-Barr virus (CAEBV) infection 3 years ago due to intermittent fever and documented Epstein-Barr virus positive serology. On physical examination, her spleen, liver, and superficial lymph nodes were not palpable. There was no sign of pulmonary infection. Initial laboratory tests were as follows: white blood cell count 0.92 × 10⁹/L, hemoglobin 66 g/L, platelet count 15 × 10⁹/L. Serum biochemistry: alanine aminotransferase 44 U/L, aspartate transaminoferase 142 U/L, albumin 26.7 g/L, triglyceride 3.02 mmol/L, and lactate dehydrogenase 1166 U/L. Coagulation indexes were as follows: prothrombin time 14.3 s, activated prothromboplastin time 65.9 s, thrombin time 32.2 s, D-dimer 18.35 mg/L, and fibrinogen 0.81 g/L. Serum ferritin level was significantly elevated to as high as 8500 ng/mL and serum soluble interleukin-2 receptor (sIL-2R) was 13,200 U/mL. On admission, her serum EBV-DNA load was 1.99 × 10³copies/mL. Computed tomography did not find any enlarged lymph nodes and the spleen and liver had a normal size. The bone marrow morphology and pathology revealed no sign of lymphoma but slight hemophagocytosis. Flow cytometry of the bone marrow aspirate found no clonal lymphoproliferation. Thus the patient was diagnosed EBV-associated hemophagocytic lymphohistiocytosis (HLH) due to fever, pancytopenia, elevated triglyceride, liver dysfunction, coagulopathy, and obviously elevated serum ferritin and sIL-2R. We initiated HLH-2004 protocol to control her HLH immediately upon diagnosis. In addition to dexamethasone, etoposide, and cyclosporin A, subcutaneous recombinant human interferon (IFN)-α2b of 300 million units was given every other day. Her temperature returned to normal soon and her laboratory indexes improved rapidly within 2 weeks. Her complete blood count, serum biochemistry, and coagulation test were fully normalized in 4 weeks, even though her serum EBV-DNA load remained at a low level of 1.02 × 10²copies/mL. We tapered off the chemotherapy gradually and her etoposide, dexamethasone, and cyclosporin A were fully stopped six weeks later. IFN-α2b was continuously given as the only maintenance therapy and it was gradually reduced to once weekly 6 months later. This patient was followed for 3 years. She remained complete remission, even if her serum EBV-DNA could always be detected between 10 and 100 copies/mL.

To the Editor:A 15-year-old girl from Chengdu (Sichuan province, China) came to our hospital in December 2019. Her mother stated that the girl’s body was thin since she was 3 years old, but no other abnormalities were noted. She visited the hospital because of developing tinnitus and hearing loss over the last 5 months. On admission, it was found that she had low subcutaneous fat and particular facial features, including small jaw, thin lips, mandibular dysplasia, and crowded teeth [Figure 1]. Her height was 1.50 m, and the body mass index (BMI) was 13.3 kg/m². Dual energy X-ray absorptiometry (DXA) scan showed a total fat mass of 6.65 kg. The calculated fat mass index (FMI) was 2.96 kg/m², indicating a fat deficit. Triglycerides level was 1.40 mmol/L, the cholesterol level was 3.08 mmol/L, and the uric acid level was 476 μmol/L. Abdominal ultrasound showed a fatty liver. The level of human growth hormone was 0.1 μg/L, and estradiol was 64 pg/mL. An oral glucose tolerance test showed that fasting serum glucose, serum glucose at 1 h after meal and serum glucose at 2 h after meal were 4.64 mmol/L, 7.75 mmol/L, and 7.12 mmol/L, respectively. Fasting serum insulin, serum insulin at 1 h after meal and serum insulin at 2 h after meal were 25.7 μU/mL, 253.6 μU/mL, and 257.4 μU/mL, respectively. Fasting serum C-peptide, serum C-peptide at 1 h after meal and serum C-peptide at 2 h after meal were 25.7 nmol/L, 253.6 nmol/L, and 257.4 nmol/L, respectively. These results indicated normal glucose tolerance with increased insulin resistance. A plain magnetic resonance imaging (MRI) scan of the internal auditory canal showed no obvious abnormalities bilaterally. Further otolaryngologic examination demonstrated sensorineural hearing loss. Craniocerebral MRI plain scan did not detect clear abnormalities, and bone density examination revealed osteoporosis. Given the special clinical manifestations of the patient, an underlying genetic disease was considered. Therefore, a trio whole-exome sequencing was performed for the patient and her parents. The results showed no abnormalities in both parents, but ade novovariation in the DNA polymerase δ1 catalytic subunit (POLD1) gene [NM_002691.3: c.1812_1814del, p. (Ser605del)] in the patient. The girl was diagnosed with the mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome based on the combination of clinical manifestations and the genetic test.

To the Editor:Hyperuricemia, the second most common metabolic disease after diabetes mellitus in China, is characterized by the elevated serum uric concentration which is due to the overactive uric acid production or underexcretion.^[1]Recent study supported the notion that hyperuricemia is implicated in renal tubular injury, subsequent tubulointerstitial fibrosis, and finally gouty nephropathy.^[2]However, the lack of a suitable and stable mouse model to study hyperuricemia and gout nephropathy delays and limits the development of mechanism research and new drugs. Further understanding of the pathogenesis of hyperuricemia and gouty nephropathy has been largely hampered by a lack of preclinical animal models that reliably capture the characteristic phenotypes of hyperuricemia and gouty nephropathy. In this study, we aimed to develop a novel mouse model for hyperuricemia and gouty nephropathy.

To the Editor:We appreciate the attentive and interesting article "Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in cornu ammonis 3 (CA3) sub-field and dentate gyrus of the hippocampus in different aged rats" written by Liet al.^[1]The authors had shown stress had age-dependent effects on behavioral responses and hippocampal brain-derived neurotrophic factor (BDNF) expression in rats. In addition, stress and age were the main factors affecting the expression of BDNF. The aged stress rats showed lower BDNF expression compared to the young stress rats at every testing time point.

In the article, "In vitroFlow Perfusion Maintaining Long-term Viability of the Rat Groin Fat Flap: A Novel Model for Research on Large-scale Engineered Tissues" , which appeared on the pages 212-7, issue 2, vol. 131 ofChinese Medical Journal,^[1]the author list, correspondence, and funding are changed to "Yang An^1,2, Kerstin Reimers¹, Christina Allmeling¹, Jie-Li Liu¹, Andrea Lazaridis¹, Strauss Sarah¹, Fang-Fei Nie², Ze-Lian Qin², Peter M. Vogt¹