2023年 · 第136卷第09期

To date, conventional morphological indicators of embryos are still used as the primary rating parameters or criteria. However, standardized and easy-to-use morphological evaluation criteria for human cleavage-stage embryos and blastocysts remain lacking. According to theIstanbul Consensus,^[1]morphological scoring systems for cleavage-stage embryos, trophectoderm (TE) cells, and inner cell mass (ICM) include three ratings, namely good, fair, and poor. However, the criteria are straightforward and less detailed, which increases the subjectivity of the embryo evaluation procedure. In this consensus, we provide a scoring system for cleavage-stage embryos and blastocysts in which the evaluative indicators are explained using illustrative images. In addition, this consensus quantifies a variety of evaluative indicators, such as the number of cells in cleavage-stage embryos and the number of TE and ICM cells in blastocysts, thereby improving the operability in practice. Simultaneously, it refines the grade of embryo assessment, defines high-quality and usable embryos, and displays abnormal morphological characteristics of embryos, which facilitates the selection of embryos for transfer. This consensus was initiated by the Chinese Association of Reproductive Medicine and compiled jointly by European and Oceanian embryologists in an effort to further optimize the quality management systems of assisted reproduction laboratories and enhance the performance of assisted reproduction technology.

Developmental dysplasia of the hip (DDH) is one of the most common diseases causing hip pain in adults and is an important cause of osteoarthritis (OA). Borderline developmental dysplasia of the hip (BDDH) is a condition that falls between a normal hip and adult DDH. In BDDH, the lateral center-edge angle (LCEA) of the acetabulum is usually defined between 18° and 25° or 20° and 25°; however, this definition remains controversial.^[1]

Wearable technology, which can continuously and remotely monitor physiological and behavioral parameters by incorporated into clothing or worn as an accessory, introduces a new era for ubiquitous health care. With big data technology, wearable data can be analyzed to help long-term cardiovascular care. This review summarizes the recent developments of wearable technology related to cardiovascular care, highlighting the most common wearable devices and their accuracy. We also examined the application of these devices in cardiovascular healthcare, such as the early detection of arrhythmias, measuring blood pressure, and detecting prevalent diabetes. We provide an overview of the challenges that hinder the widespread application of wearable devices, such as inadequate device accuracy, data redundancy, concerns associated with data security, and lack of meaningful criteria, and offer potential solutions. Finally, the future research direction for cardiovascular care using wearable devices is discussed.

With the rapid aging of the global population posing a serious problem, frailty, a non-specific state that reflects physiological senescence rather than aging in time, has become more widely addressed by researchers in various medical fields. A high prevalence of frailty is found among kidney transplant (KT) candidates and recipients. Therefore, their frailty has become a research hotspot in the field of transplantation. However, current studies mainly focus on the cross-sectional survey of the incidence of frailty among KT candidates and recipients and the relationship between frailty and transplantation. Research on the pathogenesis and intervention is scattered, and relevant review literature is scarce. Exploring the pathogenesis of frailty in KT candidates and recipients and determining effective intervention measures may reduce waiting list mortality and improve the long-term quality of life of KT recipients. Therefore, this review explains the pathogenesis and intervention measures for frailty in KT candidates and recipients to provide a reference for the formulation of effective intervention strategies.

With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.

Screening using low-dose computed tomography (LDCT) is a more effective approach and has the potential to detect lung cancer more accurately. We aimed to conduct a meta-analysis to estimate the accuracy of population-based screening studies primarily assessing baseline LDCT screening for lung cancer.

MEDLINE, Excerpta Medica Database, and Web of Science were searched for articles published up to April 10, 2022. According to the inclusion and exclusion criteria, the data of true positives, false-positives, false negatives, and true negatives in the screening test were extracted. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the literature. A bivariate random effects model was used to estimate pooled sensitivity and specificity. The area under the curve (AUC) was calculated by using hierarchical summary receiver-operating characteristics analysis. Heterogeneity between studies was measured using the Higgins I² statistic, and publication bias was evaluated using a Deeks’ funnel plot and linear regression test.

A total of 49 studies with 157,762 individuals were identified for the final qualitative synthesis; most of them were from Europe and America (38 studies), ten were from Asia, and one was from Oceania. The recruitment period was 1992 to 2018, and most of the subjects were 40 to 75 years old. The analysis showed that the AUC of lung cancer screening by LDCT was 0.98 (95% CI: 0.96-0.99), and the overall sensitivity and specificity were 0.97 (95% CI: 0.94-0.98) and 0.87 (95% CI: 0.82-0.91), respectively. The funnel plot and test results showed that there was no significant publication bias among the included studies.

Baseline LDCT has high sensitivity and specificity as a screening technique for lung cancer. However, long-term follow-up of the whole study population (including those with a negative baseline screening result) should be performed to enhance the accuracy of LDCT screening.

The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies.

The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model.

The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website (https://chris-yu.shinyapps.io/hypertension_risk_prediction/) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population.

This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.

Studies have classified muscle-invasive bladder cancer (MIBC) into primary (initially muscle-invasive, PMIBC) and secondary subtypes (initially non-muscle-invasive but progresses, SMIBC), for which controversial survival outcomes were demonstrated. This study aimed to compare the survival outcomes between PMIBC and SMIBC patients in China.

Patients diagnosed with PMIBC or SMIBC at West China Hospital from January 2009 to June 2019 were retrospectively included. Kruskal-Wallis and Fisher tests were employed to compare clinicopathological characteristics. Kaplan-Meier curves and Cox competing proportional risk model were used to compare survival outcomes. Propensity score matching (PSM) was employed to reduce the bias and subgroup analysis was used to confirm the outcomes.

A total of 405 MIBC patients were enrolled, including 286 PMIBC and 119 SMIBC, with a mean follow-up of 27.54 and 53.30 months, respectively. The SMIBC group had a higher proportion of older patients (17.65% [21/119] vs. 9.09% [26/286]), chronic disease (32.77% [39/119] vs. 22.38% [64/286]), and neoadjuvant chemotherapy (19.33% [23/119] vs. 8.04% [23/286]). Before matching, SMIBC had a lower risk of overall mortality (OM) (hazard ratios [HR] 0.60, 95% confidence interval [CI] 0.41-0.85, P = 0.005) and cancer-specific mortality (CSM) (HR 0.64, 95% CI 0.44-0.94, P= 0.022) after the initial diagnosis. However, higher risks of OM (HR 1.47, 95% CI 1.02-2.10, P = 0.038) and CSM (HR 1.58, 95% CI 1.09-2.29, P = 0.016) were observed for SMIBC once it became muscle-invasive. After PSM, the baseline characteristics of 146 patients (73 for each group) were well matched, and SMIBC was confirmed to have an increased CSM risk (HR 1.83, 95% CI 1.09-3.06, P = 0.021) than PMIBC after muscle invasion.

Compared with PMIBC, SMIBC had worse survival outcomes once it became muscle-invasive. Specific attention should be paid to non-muscle-invasive bladder cancer with a high progression risk.

The results of studies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) reconstruction on the quality of life (QoL) are still inconsistent. The aim of this trial was to compare the long-term QoL of B-I with R-Y anastomosis after curative distal gastrectomy for gastric cancer.

A total of 140 patients undergoing curative distal gastrectomy with D2 lymphadenectomy in West China Hospital, Sichuan University from May 2011 to May 2014 were randomly assigned to the B-I group (N = 70) and R-Y group (N = 70). The follow-up time points were 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after the operation. The final follow-up time was May 2019. The clinicopathological features, operative safety, postoperative recovery, long-term survival as well as QoL were compared, among which QoL score was the primary outcome. An intention-to-treat analysis was applied.

The baseline characteristics were comparable between the two groups. There were no statistically significant differences in terms of postoperative morbidity and mortality rates, and postoperative recovery between the two groups. Less estimated blood loss and shorter surgical duration were found in the B-I group. There were no statistically significant differences in 5-year overall survival (79% [55/70] of the B-I group vs. 80% [56/70] of the R-Y group, P = 0.966) and recurrence-free survival rates (79% [55/70] of the B-I group vs. 78% [55/70] of the R-Y group, P = 0.979) between the two groups. The scores of the global health status of the R-Y group were higher than those of the B-I group with statistically significant differences (postoperative 1 year: 85.4 ± 13.1 vs. 88.8 ± 16.1, P= 0.033; postoperative 3 year: 87.3 ± 15.2 vs. 92.8 ± 11.3, P= 0.028; postoperative 5 year: 90.9 ± 13.7 vs. 96.4 ± 5.6, P = 0.010), and the reflux (postoperative 3 year: 8.8 ± 12.9 vs. 2.8 ± 5.3, P = 0.001; postoperative 5 year: 5.1 ± 9.8 vs. 1.8 ± 4.7, P= 0.033) and epigastric pain (postoperative 1 year: 11.8 ± 12.7 vs. 6.1 ± 8.8, P= 0.008; postoperative 3 year: 9.4 ± 10.6 vs. 4.6 ± 7.9, P = 0.006; postoperative 5 year: 6.0 ± 8.9 vs. 2.7 ± 4.6, P = 0.022) were milder in the R-Y group than those of the B-I group at the postoperative 1, 3, and 5-year time points.

Compared with B-I group, R-Y reconstruction was associated with better long-term QoL by reducing reflux and epigastric pain, without changing survival outcomes.

ChiCTR.org.cn, ChiCTR-TRC-10001434.

Microsatellite instability (MSI) is a key biomarker for cancer immunotherapy and prognosis. Integration of MSI testing into a next-generation-sequencing (NGS) panel could save tissue sample, reduce turn-around time and cost, and provide MSI status and comprehensive genomic profiling in single test. We aimed to develop an MSI calling model to detect MSI status along with the NGS panel-based profiling test using tumor-only samples.

From January 2019 to December 2020, a total of 174 colorectal cancer (CRC) patients were enrolled, including 31 MSI-high (MSI-H) and 143 microsatellite stability (MSS) cases. Among them, 56 paired tumor and normal samples (10 MSI-H and 46 MSS) were used for modeling, and another 118 tumor-only samples were used for validation. MSI polymerase chain reaction (MSI-PCR) was performed as the gold standard. A baseline was built for the selected microsatellite loci using the NGS data of 56 normal blood samples. An MSI detection model was constructed by analyzing the NGS data of tissue samples. The performance of the model was compared with the results of MSI-PCR.

We first intersected the target genomic regions of the NGS panels used in this study to select common microsatellite loci. A total of 42 loci including 23 mononucleotide repeat sites and 19 longer repeat sites were candidates for modeling. As mononucleotide repeat sites are more sensitive and specific for detecting MSI status than sites with longer length motif and the mononucleotide repeat sites performed even better than the total sites, a model containing 23 mononucleotide repeat sites was constructed and named Colorectal Cancer Microsatellite Instability test (CRC-MSI). The model achieved 100% sensitivity and 100% specificity when compared with MSI-PCR in both training and validation sets. Furthermore, the CRC-MSI model was robust with the tumor content as low as 6%. In addition, 8 out of 10 MSI-H samples showed alternations in the four mismatch repair genes (MLH1, MSH2, MSH6, and PMS2).

MSI status can be accurately determined along the targeted NGS panels using only tumor samples. The performance of mononucleotide repeat sites surpasses loci with longer repeat motif in MSI calling.

Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits.

First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo. Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate.

Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation.

hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT.

Ovarian cancer is one of the most widespread malignant diseases of the female reproductive system worldwide. The plurality of ovarian cancer is diagnosed with metastasis in the abdominal cavity. Epithelial-mesenchymal transition (EMT) exerts a vital role in tumor cell metastasis. However, it remains unclear whether long non-coding RNA (lncRNA) are implicated in EMT and influence ovarian cancer cell invasion and metastasis. This study was designed to investigate the impacts of lncRNA AC005224.4 on ovarian cancer.

LncRNA AC005224.4, miR-140-3p, and snail family transcriptional repressor 2 (SNAI2) expression levels in ovarian cancer and normal ovarian tissues were determined using real-time quantitative polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and Transwell (migration and invasion) assays were conducted to measure SKOV3 and CAOV-3 cell proliferation and metastasis. E-cadherin, N-cadherin, Snail, and Vimentin contents were detected using Western blot. Nude mouse xenograft assay was utilized to validate AC005224.4 effects in vivo. Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-140-3p and AC005224.4 or SNAI2.

AC005224.4 and SNAI2 upregulation and miR-140-3p downregulation were observed in ovarian cancer tissues and cells. Silencing of AC005224.4 observably moderated SKOV3 and CAOV-3 cell proliferation, migration, invasion, and EMT process in vitro and impaired the tumorigenesis in vivo. miR-140-3p was a target of AC005224.4 and its reduced expression level was mediated by AC005224.4. miR-140-3p mimics decreased the proliferation, migration, and invasion of ovarian cancer cells. SNAI2 was identified as a novel target of miR-140-3p and its expression level was promoted by either AC005224.4 overexpression or miR-140-3p knockdown. Overexpression of SNAI2 also facilitated ovarian cancer cell viability and metastasis.

AC005224.4 was confirmed as an oncogene via sponging miR-140-3p and promoted SNAI2 expression, contributing to better understanding of ovarian cancer pathogenesis and shedding light on exploiting the novel lncRNA-directed therapy against ovarian cancer.

To the Editor:Venous thromboembolism (VTE) is a collective term consisting of deep venous thrombosis (DVT) and pulmonary embolism (PE). It is a major worldwide health concern as it affects 5% to 15% of hospitalized patients. Various predisposing factors for VTE occurrence include cancer, surgery, prolonged immobilization, fracture, paralysis, oral contraceptive use, and hereditary coagulopathies. Since these risk factors and the occurrence of VTE in hospitalized patients depend on the cause of hospitalization, the American College of Chest Physicians (ACCP) guidelines (9th edition) recommend different scoring scales for VTE assessments. Despite the awareness of VTE prophylaxis becoming increasingly stronger, the burden of VTE is high, which suggests a prevalence of insufficient and substandard prophylaxes. The ACCP treatment guidelines recommend an appropriate anticoagulant-based treatment regimen for at least 3 months to reduce the risk of early recurrence and death. Furthermore, in recent years, the incidence of VTE has been increasing in China, suggesting that despite the ACCP guideline’s recommendation, prophylaxis is not aggressively followed in China. Hence, we designed the current study to identify the proportion of patients who received appropriate VTE prophylaxes (those fully compliant with the ACCP guidelines, 9th edition), to determine the risk factors in previously hospitalized patients diagnosed with VTE, and to analyze the treatment pattern concerning its clinical outcomes in Chinese patients with VTE.

To the Editor:The risk factors for the development of radiographic axial spondyloarthritis (SpA) are still uncertain. Previous studies found that a high concentration of serum uric acid (SUA) leads to deposition of monosodium urate (MSU) in different joints of other rheumatic arthritis diseases except gout. Furthermore, it has been reported that gout could mimic SpA. Thus, our study explored whether the development of radiographic axial SpA is related to high SUA concentration.

To the Editor:Lung cancer leads to the largest number of cancer-associated deaths in the world. As the main means of the spreading of lung cancer, lymph node metastasis is related to the strategy for its treatment and the prognosis of the patients.^[1]According to guidelines of the National Comprehensive Cancer Network, once mediastinal lymph nodes have been involved, patients are considered to have reached an advanced stage of lung cancer, and the treatment strategy should be different.^[2]Computed tomography (CT) is a common method for the preoperative prediction of lymph node metastasis among lung cancer patients. However, not all abnormal lymph nodes can be recognized preoperatively with CT. Thus, more accurate prediction of lymph node metastasis is important for lung cancer treatment.

To the Editor:Myelosuppression is one of the most common side effects of chemotherapy. Some patients would develop long-lasting aplastic anemia (AA) even after stopping chemotherapy for over three months, due to persistent destruction of the bone marrow. As a thrombopoietin-receptor agonist, eltrombopag (EPAG) has been widely used in patients with thrombocytopenia from various origins,^[1]including those with AA secondary to chemotherapy. However, both EPAG and cyclosporin A (CsA) have been reported to possibly induce the expansion of abnormal clones or controversially increase the risk of neoplasms.^[2]Thus, the challenge was to treat severe cytopenia while preventing cancer relapse. Our study reported the efficacy and safety of EPAG with or without CsA for patients with AA secondary to chemotherapy, in an attempt to find solutions to these difficulties.

To the Editor: Testosterone is a fundamental male sex hormone produced by the testicular Leydig cells. Testosterone levels are affected by age, peaking in the 20s and 30s and gradually declining thereafter.^[1]Low testosterone level may predispose men, especially older men, to a poor prognosis or death in coronavirus disease 2019 (COVID-19).^[2]Therefore, testosterone levels have a significant impact on the health status of older men. The identification of modifiable non-drug factors affecting testosterone levels in older men is important for improving their health.

To the Editor:Schizophrenia is a progressive, debilitating disease.^[1]Safe and effective treatment performed during the acute phase is the first step to improve prognosis, and it is critically important. Aripiprazole is known as a dopamine system stabilizer, and it exerts partial agonism with high affinity at dopamine D₂and serotonin-1A (5-HT1A) receptors as well as antagonism at serotonin-2A (5-HT2A) receptors.^[2]It has been shown to be efficacious in amelioration of both positive and negative symptoms of acute schizophrenia, and it shows better tolerance than most antipsychotics.^[3]We conducted a real-world study to further confirm the efficacy and safety of aripiprazole in patients with acute episodes of schizophrenia in China and tried to explore the clinical variables, including various drug regimens, which may be correlated with the efficacy of aripiprazole, and provide a basis for the optimization of aripiprazole treatment for patients with acute schizophrenia.

To the Editor:Globally, acute kidney injury (AKI) is a common life-threatening condition. AKI is more prevalent in elderly patients, with increasing mortality rates. Compared with younger patients, older patients with AKI have a higher risk of persistent injury and poorer prognoses.^[1]Older individuals often have comorbidities, increasing their susceptibility to AKI. Kidney Disease: Improving Global Outcomes (KDIGO) criteria define and stage AKI based on the higher stage of AKI defined by either serum creatinine (SCr) level or urine output (UO).^[2]However, the record of UO is difficult to access in clinic, the data on the value of UO combined with SCr for AKI diagnosis or prognosis in elderly patients are lacking. Therefore, the objectives of this study were to investigate whether UO would influence the classification of AKI and improve the accuracy of prediction of the clinical prognosis in elderly patients.

To the Editor: Duchenne muscular dystrophy (DMD) is a rare X-linked inherited disorder caused by dystrophin deficiency, which results in sarcolemmal fragility and degeneration of skeletal and cardiac myocytes.^[1]Cardiac involvement is manifested as DMD cardiomyopathy, which is the leading cause of disease-related morbidity and mortality among DMD patients.^[2]However, the signs and symptoms of cardiomyopathy frequently are subtle and often overlooked during the ambulatory and early non-ambulatory stages. Therefore, non-invasive imaging methods are recommended for the assessment of myocardial involvement of DMD patients in the updated diagnosis and management statement, and echocardiography (Echo) and cardiac magnetic resonance (CMR) are two of the most commonly used imaging methods.^[3]However, conventional Echo cannot evaluate the characteristics of myocardial tissue and plays a limited role in early diagnosis. CMR with multiple sequences and parameters allows detailed feature evaluation, and especially the evaluation of myocardial fibrosis by late gadolinium enhancement (LGE) is highly consistent with pathology. Previous studies have reported the assessment of myocardial fibrosis in DMD patients by LGE,^[4,5]but studies investigating the prevalence of myocardial fibrosis in DMD patients during the first decade of life is still lacking. Moreover, DMD is a multisystem disease, loss of dystrophy protein function could occur in skeletal muscle and cardiomyocytes. In practice, individuals with DMD start skeletal muscle management early but are not referred to a cardiac specialist until late in the disease. Therefore, it is important to clarify the association between skeletal muscle involvement and myocardial involvement in the early stages of disease, which may help clinicians start multidisciplinary management earlier and improve the quality of life of patients further. In the current study, the prevalence of LGE presence at the first decade life of DMD patients was described. Logistic regression analysis was used to determine the association factors of LGE presence.