2024年 · 第137卷第16期

Radiotherapy has been part of standard preoperative treatment for locally advanced (stage II-III) rectal cancer for over 30 years. Although preoperative radiotherapy has been proven to reduce local recurrence, it seriously affects quality of life and fails to improve long-term survival. With the introduction of total mesorectal excision (TME), local recurrence has dramatically decreased, and it is debatable whether the old wine still fits the new bottle. In this paper, we discuss this viewpoint in the context of literature and over 10 years of clinical studies in our center.

Fatty acid synthase (FASN) is an essential molecule in lipid metabolic pathways, which are crucial for cancer-related studies. Recent studies have focused on a comprehensive understanding of the novel and important regulatory effects of FASN on malignant biological behavior and immune-cell infiltration, which are closely related to tumor occurrence and development, immune escape, and immune response. FASN-targeting antitumor treatment strategies are being developed. Therefore, in this review, we focused on the effects of FASN on tumor and immune-cell infiltration and reviewed the progress of related antitumor therapy development.

The usage of electronic cigarettes (e-cigarettes) sparked an outbreak of unidentified vaping-related lung disease in the US during late 2019. With e-cigarettes becoming more and more popular, smokers have more options other than conventional cigarettes. Under these circumstances, a comprehensive evaluation of the general safety of new tobacco and tobacco-related products, represented by e-cigarettes, to human health is necessary. In this review, we summarize the current research on potential negative impacts of e-cigarette exposure on human health. In particular, studies detailing the relationship between e-cigarettes and the digestive system are summarized, with mechanisms mainly including hepatic metabolic dysfunction, impaired gut barrier, and worsened outcomes of inflammatory bowel disease (IBD). Although believed to be safer than traditional cigarettes, e-cigarettes exert adverse effects on systemic health and induce the development of multiple diseases including asthma, cardiovascular disease, and IBD. Moreover, nicotine-containing e-cigarettes have a negative impact on the childhood development and increase the risk of arterial stiffness compared to the non-nicotine e-cigarettes. However, non-nicotine e-cigarette components have detrimental effects including promoting liver damage and metabolic disorders.

Biomolecular aggregation within cellular environments via liquid–liquid phase separation (LLPS) spontaneously forms droplet-like structures, which play pivotal roles in diverse biological processes. These structures are closely associated with a range of diseases, including neurodegenerative disorders, cancer and infectious diseases, highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis, and exploring potential therapeutic interventions. In this review, we delineate recent advancements in LLPS research, emphasizing its pathological relevance, therapeutic considerations, and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations. Additionally, we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability. By providing comprehensive insights into current LLPS-related bioinformatics resources, this review highlights its implications for human health and disease.

In East Asia, Helicobacter pylori (H. pylori) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance in H. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance in H. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations.

We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance in H. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance, H. pylori, and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies.

We identified 15 observational studies involving 4831 H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance in H. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40–62%) for metronidazole; 37% (95% CI: 20–53%) for clarithromycin; 19% (95% CI: 11–28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21–36%) and 10% (95% CI: 7–14%), highlighting the potential for diverse resistance patterns.

H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem.

PROSPERO, No. CRD42023402510.

In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable.

We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.

These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes.

Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Interpreting genes of interest is essential for identifying molecular mechanisms, but acquiring such information typically involves tedious manual retrieval. To streamline this process, the fanyi package offers tools to retrieve gene information from sources like National Center for Biotechnology Information (NCBI), significantly enhancing accessibility. Additionally, understanding the latest research advancements and sharing achievements are crucial for junior researchers. However, language barriers often restrict knowledge absorption and career development. To address these challenges, we developed the fanyi package, which leverages artificial intelligence (AI)-driven online translation services to accurately translate among multiple languages. This dual functionality allows researchers to quickly capture and comprehend information, promotes a multilingual environment, and fosters innovation in academic community. Meanwhile, the translation functions are versatile and applicable beyond biomedicine research to other domains as well. The fanyi package is freely available at https://github.com/YuLab-SMU/fanyi.

Digestive system cancers constitute a significant number of cancer cases, but their burden is not uniform. As Global Cancer Observatory (GLOBOCAN) 2022 has recently updated its estimates of cancer burden, we aimed to investigate the burden of six major digestive system cancers both worldwide and in China, along with geographical and temporal variations in cancer-specific incidence and mortality.

We extracted data on primary cancers of the esophagus, stomach, colorectum, liver, pancreas, and gallbladder from the GLOBOCAN database for 2022. Age-standardized incidence and mortality rates were calculated and stratified by sex, country, region, and human development index (HDI). We used the 2022 revision of the World Population Prospects (United Nations) to obtain demographic data for various age groups in China from 1988 to 2012 and used the joinpoint model and the average annual percentage change (AAPC) to analyze cancer incidence trends in China.

In 2022, the estimated global incidence of digestive system cancers reached 4,905,882, with an estimated 3,324,774 cancer-related deaths. Colorectal cancer was most prevalent in terms of incidence and mortality. There was a significant correlation between the burden of gastrointestinal cancers and country HDI. From 1988 to 2012, the incidence of esophageal, gastric, and liver cancers declined in China, whereas colorectal and pancreatic cancer incidences continued to increase. By 2050, colorectal and liver cancers are projected to remain the leading cancer types in China in terms of incidence and mortality, respectively.

Digestive system cancers remain a significant public health challenge globally and in China. Although progress has been made in the prevention and control of some cancers, the burden of digestive system cancers persists. The implementation of tertiary prevention strategies must be intensified to reduce the incidence and mortality of digestive system cancers, mitigating their impact on public health.

The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.

In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.

The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI.

CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

As a radical treatment for hepatocellular carcinoma (HCC), liver transplantation (LT) has become an ideal treatment option for certain HCC patients. For patients beyond the Milan criteria, high HCC recurrence risk is a vital factor affecting the prognosis. Sirolimus, a first-generation mammalian target of rapamycin (mTOR) inhibitor, decreased recurrence rates and prolonged overall survival (OS) compared with calcineurin inhibitors (CNI)-based mTOR inhibitor-free immunosuppression.^[1]However, some patients taking sirolimus after LT regularly do still have HCC recurrence in clinical practice. Thus, predicting the efficacy of sirolimus from the perspective of molecular pathology is expected to break through this bottleneck.

Spinal muscular atrophy (SMA), a neurodegenerative disorder caused by mutations in survival motor neuron 1 (SMN1) resulting in reduced expression of the survival motor neuron (SMN) protein, is inherited in an autosomal recessive manner. SMA type 1 is the most frequent subtype of SMA characterized by onset before 6 months of life, inability to achieve independent sitting, and rapidly progressive respiratory and bulbar deterioration, causing a mortality of >90% before 2 years of age.^[1]Currently, there have been two lifelong splice-modifying therapies (nusinersen and risdiplam), and a single-dose gene replacement therapy via intravenous onasemnogene abeparvovec for SMA type 1 patients, approved by the US Food and Drug Administration (FDA).^[2]

To the Editor: Endometrial cancer (EC) is the sixth most common cancer diagnosed in women, and its prevalence is reportedly increasing worldwide. Endometrial clear cell carcinoma (ECCC) accounts for 2–5% of all EC, and is a rare but ominous subtype of high-risk EC that has a poorer prognosis and exhibits greater chemoresistance. Owing to the rarity of ECCC, few clinical trials have included patients with this disease exclusively, and limited data are available regarding its pathogenesis and clinical progression compared with other more common subtypes of EC.

To the Editor:Delirium is a common postoperative complication associated with multiple adverse clinical outcomes in older patients.^[1]According to the time of onset, delirium in the postoperative stage can be divided into emergence delirium (ED) and postoperative delirium (POD). ED occurs during or immediately after awakening from general anesthesia, whereas POD is usually found during postoperative days 1–7. Assessing patients for ED provides the first clue of a possible postoperative neurocognitive disorder.^[2]Dexmedetomidine (DEX) is a highly selective α-2 receptor agonist that is increasingly used in the perioperative period to induce sedation, analgesia, anxiolysis, and sympathetic tone suppression. Previous studies suggested that DEX may be an effective intraoperative adjuvant drug, which can reduce agitation and improve recovery after orthopedic surgery in older patients.^[3,4]However, few studies focused on the relationships between DEX and ED. This randomized controlled trial (RCT) aims to explore the relationships between intraoperative DEX administration and the incidence of ED in older patients undergoing lower limb orthopedic surgery, and examine the effects of DEX on the electroencephalogram (EEG) trajectories of older patients during the emergence period and its correlation with ED occurrence.

To the Editor:Breast cancer (BC) is the most common cancer in women, which affects 2.26 million people annually, with 680,000 fatalities. Around 70% of cases involve estrogen-activated estrogen receptors (ER), which promote tumor growth through gene regulation and cellular signaling. ER reactivation without ligands contributes to therapy resistance. Endocrine resistance in estrogen receptor-positive (ER+) breast tumors can result from mutations in ER, altered interactions with coactivators/corepressors, or crosstalk with growth factor receptors and oncogenic pathways.^[1]Additionally, long non-coding RNAs (lncRNAs) are diverse molecules with distinct expression patterns in different cancer types, playing critical roles in tumorigenesis.^[2]Notably, actin gamma 1 pseudogene (AGPG) is emerging as a noteworthy lncRNA that holds promise as a new therapeutic target intended for the effective management of endocrine-resistant BC.

To the Editor: Core decompression (CD), the predominant hip-preserving procedure for pre-collapse osteonecrosis of the femoral head (ONFH), is renowned for its improved short-term outcomes and relatively low postoperative complication rates; however, the reported medium-to-long-term survival rates in the literature vary and are a subject of controversy. Consequently, we conducted a large, prospective cohort study to assess the frequency and timing of conversion from CD to total hip arthroplasty (THA) and the factors associated with it.

To the Editor: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a relapsing-remitting disease course that warrants flexible dosing.^[1,2]In China, abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is approved at a 100 mg starting dose for adults with refractory moderate-to-severe AD who did not inadequately respond to other systemic therapies (i.e., corticosteroids or biologics), or for whom these treatments are not advisable. If the response achieved with abrocitinib 100 mg is inadequate, 200 mg dosing can be considered, which could be administered as a short-term treatment (≤12 weeks).^[3]The phase 3 JADE REGIMEN trial (Clinicaltrials.gov, NCT03627767) evaluated maintenance of response with continuous-dose abrocitinib (200 mg), reduced-dose abrocitinib (100 mg), or drug withdrawal (placebo) in patients with moderate-to-severe AD who responded to abrocitinib induction therapy.^[4]Here, we aimed to characterize the efficacy and safety of abrocitinib in the Chinese mainland subgroup within JADE REGIMEN.

To the Editor:Despite dramatic improvements in the prognosis of pediatric liver transplantation (LT), postoperative complications are still a leading cause of death in grafts and patients. Child recipients were shown to have a higher risk of thrombotic complications than in adult recipients, due to differences in etiology, narrowed hepatic vessels due to hypoplasia, more meticulous surgical techniques, and other factors.^[1]Thrombotic complications include hepatic artery thrombosis (HAT), portal vein thrombosis (PVT), and venous outflow tract obstruction (VOTO) including inferior vena cava obstruction and hepatic venous outflow obstruction. Currently, there is still a 3–10% incidence of PVT and a 5–15% incidence of HAT, and VOTO varies between 1% and 13%.^[2]Clinicians tend to overemphasize antithrombotic therapy to reduce the risk of thrombosis after pediatric LT, which leads to a higher risk of bleeding and warrants better antithrombotic management. Regarding the difficult problem of balancing thrombotic events and bleeding events, clinicians urgently need to perceive the risk of postoperative thrombosis to assist in optimizing antithrombotic regimens and there is no available quantitative risk assessment tool to intuitively identify high-risk children conveniently in clinical practice.

To the Editor: Psoriasis is a common, chronic inflammatory skin disease occurring worldwide and presenting at any age.^[1]Biologics are the most important therapeutic advances in psoriasis treatment.^[2]With the development of 16S rRNA sequencing technology, the association between psoriasis and intestinal flora has been gradually revealed. Some bacteria secrete short-chain fatty acids (SCFAs) with anti-inflammatory properties, serving as active microbial metabolites that regulate the function of immune cells in the intestine and other tissues.^[3]However, the impact of biological treatment on gut microbiota and related functional changes in psoriasis patients remains unclear. Our study aimed to explore the effects of biological treatments on the intestinal microbiota of psoriasis patients.

To the Editor:Glaucoma is a leading cause of irreversible blindness worldwide.^[1]Trabeculectomy with mitomycin C (MMC) has been the standard surgical intervention for reducing intraocular pressure (IOP) and slow down the progression of glaucoma.^[2]However, some serious complications with devastating consequences can occur after trabeculectomy, such as bleb-related infections, suprachoroidal hemorrhage, vitreous hemorrhage, and malignant glaucoma. Over the last decade, many novel ophthalmic surgical devices have been used in glaucoma. The XEN45 microstent (Allergan, Dublin, CA, USA) is a hydrophilic cross-linked porcine gelatin stent. It is implanted ab-interno, draining the aqueous humor into the subconjunctival space without the need to form a conjunctival flap, scleral flap, or iridectomy. Penetrating canaloplasty (PCP), first proposed by Lianget al^[3], is a relatively new Schlemm’s canal-based surgery. The procedure integrates the trabeculectomy procedures into canaloplasty, creating a direct communication between the anterior chamber and the ostia of Schlemm’s canal to restore the internal drainage of aqueous humor. PCP restores the aqueous humor outflow in a bleb-independent manner and does not require MMC. The purpose of this study is to compare the surgical success and postoperative complications among XEN45 implantation, trabeculectomy with MMC, and PCP in Chinese patients with open-angle glaucoma over a 12-month period.

To the Editor:Insomnia affects 30%–50% of adults globally, leading to diminished quality of life and increased risks of developing physically and mentally demanding disorders.^[1]Previous research, primarily in Western populations, reported the association between insomnia and poor diet quality, characterized by higher energy intake, lower vegetable consumption, and a preference for fatty foods, risk factors contributing to major chronic conditions.^[2]This association, however, remains under-explored in Asian populations, where dietary patterns significantly differ. Additionally, research indicated that poor sleep quality was often associated with nocturnal behaviors like late-night eating and breakfast skipping.^[3,4]Consuming breakfast is generally associated with better diet quality, while night-eating tends to be related to poorer diet quality. Further, the specific impact of insomnia on such eating behaviors, and their role in potentially mediating the relationship between insomnia and diet quality, has not been thoroughly explored, particularly in community-based populations. We thus conducted a large-scale community-based study in China to evaluate whether participants with insomnia were more likely to have lower diet quality and unhealthy behaviors (i.e., frequently engaging in night-eating and breakfast-skipping). We further investigated whether these eating behaviors mediated the potential association between insomnia and diet quality.

To the Editor: Polycystic ovary syndrome (PCOS), characterized by oligo-anovulation, hyperandrogenism, and polycystic ovaries, is the most common endocrinopathy affecting 5–15% of women of reproductive age.^[1,2]It can result in a wide range of endocrine and metabolic disorders, including anovulatory infertility, insulin resistance, impaired glucose tolerance, diabetes, obesity, dyslipidemia, and cardiovascular disease, which can occur in different combinations and with different intensities.^[2]Thyroid dysfunction is another common endocrine disorder associated with ovarian dysfunction, menstrual irregularities, subfertility, and infertility in women of reproductive age. The most prevalent cause of thyroid dysfunction is autoimmune thyroid disease (AITD), which is very frequent in infertile women and associated with adverse assisted reproduction technology (ART) outcomes.^[3]Considering the high prevalence of AITD and PCOS in reproductive-age women, the common etiology and pathogenesis have been elucidated, including the polymorphisms of susceptibility genes, thymus disorders, vitamin D deficiency, and sex hormone dysregulation.^[4]Several studies have elucidated the negative association between thyroid function and autoimmunity indicators andin vitrofertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and pregnancy outcomes.^[3]However, there is still a lack of evidence on the associations between thyroid function and autoimmunity indicators and IVF/ICSI outcomes among PCOS women. We aimed to investigate the potential effects of thyroid function and autoimmunity indicators on IVF/ICSI early development and pregnancy outcomes among euthyroid PCOS women.