2024年 · 第137卷第06期

When patients having major surgery reach the post-anaesthesia care unit, families naturally assume that they have survived the most dangerous part of the perioperative experience. Their assumption is wrong. Mortality in the 30 days after surgery is 140 times higher than intraoperative mortality.^[1,2]In fact, if the month after surgery were considered a disease, it would be the world’s third leading cause of death.^[3]

Colonic transendoscopic enteral tubing (TET) is an interventional intestine therapeutic procedure. The colonic TET technique represents a novel drug delivery route, interventional diagnosis and therapy, and paradigm for concept validation, showing broad prospects in research and practice. Since its first meeting at the China Gut Conference in 2023, our panel of experts has held a series of discussions on TET’s concept, breakthroughs, and future. We strive to lay the groundwork for further establishing the TET Study Group for designing multicenter studies and developing relevant consensus or guidelines.

Except a few tissues such as the cornea and cartilage that are avascular, blood vessels constitute a significant proportion of tissue masses in virtually all organs. Under physiological conditions, the adult vasculature remains quiescent to retain tissue and organ homeostatic functions. Too few or too many blood vessels are associated with the onset and progression of many diseases. In response to injuries, most tissues undergo repair by switching on angiogenesis, a key process of new blood vessel formation.^[1]Similarly, angiogenesis is often active in pathological tissues, including tumors and ischemic tissues to aggravate disease progression. To induce neovascularization, angiogenic tissues produce various growth factors and cytokines that primarily target endothelial cells and perivascular cells.^[2]Targeting these angiogenic factors provides an attractive approach for treatment of a number of malignant and non-malignant diseases such as cancer and ophthalmologic diseases. In fact, antiangiogenic drugs are routinely used in the clinic for the treatment of various cancers and ocular diseases.^[2]Conversely, stimulation of angiogenesis by delivery of proangiogenic factors also provides an exciting opportunity for the treatment of ischemic diseases such as ischemic myocardium after cardiac infarction and wound healing.^[3]In a series of review articles, we describe the updated knowledge of angiogenesis research and discuss clinical implications, challenging issues, and possible solutions. We provide a few examples of pro- and anti-angiogenic therapies for treatment of various diseases, including cancer, ophthalmological disease, cardiovascular disease, and metabolic disease [Figure 1]. Because the topic of angiogenesis in regulating lipid metabolism and metabolic diseases was recently discussed in another issue of the Chinese Medical Journal,^[4]we exclude this topic in this issue. This special issue is also dedicated to honor and celebrate Dr. Judah Folkman for his initial hypothesis that has led to half a century of groundbreaking achievements in angiogenesis research and clinical success.

Anti-cancer therapies usually focus on tumor cells, but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression, which may be the prognostic factors and potential therapeutic targets. Cancer-associated fibroblasts (CAFs) are the essential component in the tumor environment, exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis, immune systems, and metabolism. Single-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity, and many subtypes have been defined. However, the precise functions of these subtypes need to be studied and validated. Studies of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic targets. Some clinical trials, including phase III trials targeting CAFs, have been performed recently. However, few of these trials have generated promising results, which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown, and in-depth investigations of CAFs should be performed. This review summarizes the research on CAFs, focusing on the heterogeneity of their phenotypes and functions, specific signaling pathways, and the therapeutic strategies involving CAFs. Additionally, we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

Cochlear spiral ganglion neurons (SGNs) are bipolar ganglion cells and are the first neurons in the auditory transduction pathway. They transmit complex acoustic information from hair cells to second-order sensory neurons in the cochlear nucleus for sound processing. Injury to SGNs causes largely irreversible hearing impairment because these neurons are highly differentiated cells and cannot regenerate, making treatment of sensorineural hearing loss (SNHL) arising from SGN injury difficult. When exposed to ototoxic drugs or damaging levels of noise or when there is loss of neurotrophic factors (NTFs), aging, and presence of other factors, SGNs can be irreversibly damaged, resulting in SNHL. It has been found that NTFs and stem cells can induce regeneration among dead spiral ganglion cells. In this paper, we summarized the present knowledge regarding injury, protection, and regeneration of SGNs.

Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.

Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation.

Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI (P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models (P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species (P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD).

YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.

In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.

In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%).

COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

Acute pulmonary embolism (APE) is a fatal cardiovascular disease, yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs. A simple, objective technique will help clinicians make a quick and precise diagnosis. In population studies, machine learning (ML) plays a critical role in characterizing cardiovascular risks, predicting outcomes, and identifying biomarkers. This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.

This is a single-center retrospective study. Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets. A total of 8 ML models, including random forest (RF), Naïve Bayes, decision tree, K-nearest neighbors, logistic regression, multi-layer perceptron, support vector machine, and gradient boosting decision tree were developed based on the training set to diagnose APE. Thereafter, the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies, including the Wells score, revised Geneva score, and Years algorithm. Eventually, the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic (ROC) analysis.

The ML models were constructed using eight clinical features, including D-dimer, cardiac troponin T (cTNT), arterial oxygen saturation, heart rate, chest pain, lower limb pain, hemoptysis, and chronic heart failure. Among eight ML models, the RF model achieved the best performance with the highest area under the curve (AUC) (AUC = 0.774). Compared to the current clinical assessment strategies, the RF model outperformed the Wells score (P = 0.030) and was not inferior to any other clinical probability assessment strategy. The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726.

Based on RF algorithm, a novel prediction model was finally constructed for APE diagnosis. When compared to the current clinical assessment strategies, the RF model achieved better diagnostic efficacy and accuracy. Therefore, the ML algorithm can be a useful tool in assisting with the diagnosis of APE.

Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.

We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).

Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence.

Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate. Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome, who subjected to preimplantation genetic testing for aneuploidy (PGT-A) treatment. However, it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.

From February 2020 to May 2021, we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos, the clinical information of couples, and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment. Initially, we developed a novel deep learning model called the Attentive Multi-Focus Selection Network (AMSNet) to analyze time-lapse videos in real time and predict blastocyst formation. Building upon AMSNet, we integrated additional clinically predictive variables and created a second deep learning model, the Attentive Multi-Focus Video and Clinical Information Fusion Network (AMCFNet), to assess the euploidy status of embryos. The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements. The receiver operating characteristic curve (ROC) was used to evaluate the superiority of the model.

A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task, and 1422 qualified blastocysts received PGT-A (n = 589) or PGT for chromosomal structural rearrangement (PGT-SR, n = 833) were enrolled for the euploidy assessment task in this study. The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy. The real-time accuracy for AMSNet to predict blastocyst formation reached above 70% on the day 2 of embryo culture, and then increased to 80% on the day 4 of embryo culture. Combing with 4 clinical features of couples, the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement.

Integrating seven focal raw time-lapse images of embryos and parental clinical information, AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.

Spinal injuries are an urgent public health priority; nevertheless, no China-wide studies of these injuries exist. This study measured the incidence, prevalence, causes, regional distribution, and annual trends of spinal injuries in China from 1990 to 2019.

We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 to estimate the incidence and prevalence of spinal injuries in China. The data of 33 provincial-level administrative regions (excluding Taiwan, China) provided by the National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention (CDC) were use to systematically analyze the provincial etiology, geographical distribution, and annual trends of spinal injuries. The Bayesian meta-regression tool DisMod-MR 2.1 was used to ensure the consistency among incidence, prevalence, and mortality rates in each case.

From 1990 to 2019, the number of living patients with spinal injuries in China increased by 138.32%, from 2.14 million to 5.10 million, while the corresponding age-standardized prevalence increased from 0.20% (95% uncertainty interval [UI]: 0.18-0.21%) to 0.27% (95% UI: 0.26-0.29%). The incidence of spinal injuries in China increased by 89.91% (95% UI: 72.39-107.66%), and the prevalence increased by 98.20% (95% UI: 89.56-106.82%), both the most significant increases among the G20 countries; 71.00% of the increase could be explained by age-specific prevalence. In 2019, the incidence was 16.47 (95% UI: 12.08-22.00, per 100,000 population), and the prevalence was 358.30 (95% UI: 333.96-386.62, per 100,000 population). Based on the data of 33 provincial-level administrative regions provided by CDC, age-standardized incidence and prevalence were both highest in developed provinces in Eastern China. The primary causes were falls and road injuries; however, the prevalence and specific causes differed across provinces.

In China, the overall disease burden of spinal injuries increased significantly during the past three decades but varied considerably according to geographical location. The primary causes were falls and road injuries; however, the prevalence and specific causes differed across provinces.

Mild traumatic brain injury (mTBI) is a common neurological trauma that can lead to cognitive impairment. The sirtuin-1 (SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) pathway has been reported to have neuroprotective effects in rats with craniocerebral injury. We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI, focusing on the SIRT-1/PGC-1α/mitochondrial pathway.

We included forty 6-week-old male Sprague-Dawley rats in this study. Rats were randomly divided into four groups: controlled cortical impactor (CCI, n = 10), sham operation (sham, n = 10), electroacupuncture-treated CCI (CCI+EA, n = 10), and electroacupuncture-treated sham (sham+EA, n = 10) group. Randomization was performed by assigning a random number to each rat and using a random number table. The mTBI rat model was established using a controllable cortical impactor. Electroacupuncture therapy was performed on the back of rats, by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment. We evaluated spatial learning and memory functions with the Morris water maze test. We performed quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, adenosine triphosphate (ATP) determination, and mitochondrial respiratory chain complex I (MRCC I) determination on rat hippocampal tissue. We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays, and compared differences between groups using bilateral Student’s t-tests.

Compared with the sham group, SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group (P <0.01). Although this expression was upregulated following electroacupuncture, it did not reach the levels observed in the sham group (P <0.05). Compared with the sham group, MRCC I and ATP levels in the CCI group were significantly reduced, and increased after electroacupuncture (P <0.01). In the Morris water maze, electroacupuncture reduced the incubation period of rats and increased average speed and number of crossing platforms (P <0.05).

Electroacupuncture may improve cognitive function in the mTBI rat model by regulating the SIRT-1/PGC-1α/mitochondrial pathway.

The incidence of well-differentiated gastric neuroendocrine tumors (G-NET) is increasing annually, and while they have a good prognosis and low mortality rate, their high recurrence rate makes treatment options controversial. This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET.

We performed a multicenter, retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union Medical College Hospital, Yantai Yuhuangding Hospital, and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023. Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis.

After a median follow-up of 49 months, the overall recurrence rate among the 94 G-NET patients was 14% (13/94). The recurrence rates of endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), somatostatin analog (SSA) therapy, and surgery were 43% (6/14), 10% (5/49), 5% (1/22), and 11% (1/9), respectively. Post-treatment recurrence rates were significantly different (P = 0.014) among four treatments (EMR, ESD, SSA, and surgery), and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group. From the second month onward, SSA therapy considerably reduced the gastrin levels from 1081.0 (571.5, 2472.8) pg/mL to 461.5 (255.3, 795.0) pg/mL (Z = -3.521, P <0.001). Both chi-squared test and multifactorial logistic regression analysis suggested that among the clinicopathological parameters studied, only the pre-treatment gastrin level (P = 0.018 and 0.005) and the type of treatment (P = 0.014 and 0.017) were significantly associated with G-NET recurrence.

Individualized treatment strategies may reduce the risk of relapse after G-NET treatment. Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions, and it substantially decreases the incidence of post-treatment recurrence.

Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.

The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4⁺) T-cell counts, CD8⁺ T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed.

The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log₁₀-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log₁₀-unit range. Total HIV DNA in CD4⁺ T cells was positively associated with integrated HIV DNA (r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4⁺ T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8⁺ T-cell counts.

This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.

Osteonecrosis of the femoral head (ONFH) is mainly caused by a decrease in the vascular supply to the subchondral bone of the femoral head, leading to the death of bone cells, degeneration and necrosis of the subchondral bone, and eventually collapse of the femoral head.^[1]Early and accurate diagnosis is the key to successful hip-preserving therapy, and the size/location of necrosis is the main determinant for ONFH treatment. Previous studies have shown that many hip-preserving therapies achieved satisfactory results in ONFH patients with Association Research Circulation Osseous (ARCO) I-II. When ONFH progresses to ARCO IV with clinical manifestations of osteoarthrosis, total hip arthroplasty (THA) may be the only option. However, the optimal therapy for osteonecrosis of the collapsed femoral head (ARCO III) remains unknown.^[2]For these patients with osteonecrosis and collapse of the femoral head, especially middle-aged patients, the majority of scholars believe that surgical intervention should be performed as soon as possible to restore structural stability of the femoral head, relieve pain, and stop or delay progression.

To the Editor:Atopic dermatitis (AD) is a chronic, relapsing inflammatory dermatosis with impairment of skin barrier function and immune dysfunction that affects both children and adults. It is characterized by eczematous lesions, pruritus, sleep disturbance, and diminished quality of life. Management of mild AD relies on emollients, topical corticosteroids, topical calcineurin inhibitors, and phototherapy, while systemic corticosteroids, immunosuppressive agents, and biologics are used for severe refractory cases.^[1]Systemic corticosteroids and immunosuppressants have many undesirable side effects. Patients with moderate-to-severe AD who do not respond adequately to topical therapies have few effective treatment options.

To the Editor: Coronavirus disease 2019 (COVID-19) has evolved into a global pandemic, with over 700 million confirmed cases worldwide and still mounting.^[1]The clinical impact of this pandemic is immense, given the wide spectrum of disease manifestation, ranging from mild respiratory symptoms to severe pulmonary infections. Identifying high-risk individuals, especially during their initial encounters in clinics and hospital emergency services, is crucial to provide timely effective treatment. Therefore, the timely risk stratification of COVID-19 patients in the emergency room can greatly benefit both infected individuals and healthcare professionals.^[2]This study aims to identify features of serious COVID-19 infection at presentation that may lead to mortality of the patients.

To the Editor:Current guidelines recommend that for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT), preferably involving powerful P2Y₁₂receptor inhibitors, including ticagrelor or prasugrel, should be used for at least 12 months.^[1,2,3]However, there is a lack of relevant evidence regarding the feasibility of de-escalation treatment and specific DAPT treatment regimens for ACS patient populations with high ischemic risk.

To the Editor: Pathological cardiac hypertrophy is commonly stimulated by stress or induced by cardiovascular diseases, such as hypertension and myocardial infarction. A sustained pathological hypertrophic response can lead to declines in diastolic and systolic functions and eventually develop heart failure. Angiotensin II (Ang II) can mediate cardiac hypertrophy through the angiotensin II type 1 receptor (AT1R).^[1]Angiotensin receptor-like 1 (APJ), a member of the seven-transmembrane G protein-coupled receptor (GPCR) family, has high homology with AT1R in amino acid sequence (identity: 27.56%, similarity: 74.28%) [Supplementary Figure 1A, http://links.lww.com/CM9/B887]. Apelin is the endogenous ligand of APJ. Published studies report that the Apelin/APJ system participates in various physiological processes of myocardial cells. In the previous study, we demonstrated that the Apelin-13/APJ system promotes the development of cardiac hypertrophy.^[2]Therefore, both Ang II/AT1R and Apelin/APJ may contribute to the development of cardiac hypertrophy.

To the Editor: In 1996, Parodiet al^[1]introduced the technique of fenestrated endovascular aneurysm repair (f-EVAR) for treatment of pararenal abdominal aortic aneurysms. They use physician modified stent grafts (PMSGs) for fenestration, which allows for stent grafts to gain sufficient proximal sealing zones and maintain the blood perfusion of visceral arteries.^[2]Stent grafts used in the f-EVAR technique developed from PMSGs to Company Modified Devices (CMDs) and off-the-shelf devices.^[3]To improve the precision of PMSGs and shorten the time of stent graft modification, various techniques that assist in the process of fenestration have been researched and developed, including 3-dimensional (3D) printing technique, the Mixed Reality (MR) technique, and the 3D parametric surface planar topological guide plate. This article describes the current status and future development of these techniques.

To the Editor: A 62-year-old woman presented to the dermatology department with a 5-month history of multiple painless cutaneous abscesses and ulcers [Figure 1A], occurring 1 month after a transvaginal hysterectomy due to uterine prolapse. Her general condition was good before and after the surgery, with no abnormal physical signs apart from metroptosis. She reported no fever, night sweat, cough, or abdominal pain, but 10 kg weight-loss. She has no history of diabetes, autoimmune diseases, or chronic infectious diseases. There was no similar illness in her family. Physical examination showed multiple subcutaneous nodules with fluctuation measuring 3.0-5.0 cm on the trunk and upper arms, as well as multiple cutaneous ulcers with yellow pus. No enlarged lymph node was palpated. Laboratory tests showed anemia, elevated leukocyte count, and increased C-reactive protein (CRP). Fungal and bacterial cultures of pus drained from a nonulcerative lesion were negative, whileMycobacterium aviumwas detected by real-time quantitative polymerase chain reaction. Purified protein derivative (PPD) test was negative and chest X-ray showed increased lung markings. Abdominal and pelvic computed tomography scan showed a mass at the vaginal stump, upper ureteral dilation, and bilateral hydronephrosis, whereas urine volume and serum creatinine were normal. Skin biopsy demonstrated granuloma with lymphocytes and neutrophils infiltration. Both acid-fast staining and periodic acid-Schiff staining of tissue for microorganisms were negative. The tentative diagnosis of disseminated nontuberculous mycobacteria (NTM) infection was made, although the evidence was not conclusive. The golden standard for diagnosing NTM is a positive culture of NTM but obtaining the result would take approximately three months and skins lesions of the patient were too severe to wait. She was empirically treated with clarithromycin, rifampicin, and ethambutol.