2023年 · 第136卷第22期

Over the past few years, the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health. Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases. This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status. By surveying the latest literature, we present a detailed overview of virome alterations observed in various immunodeficiency conditions. We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals. Furthermore, this review explores the clinical relevance of virome studies in the context of immunodeficiency, highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.

Although antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited. In recent years, with the technological progress and great success of chimeric antigen receptor (CAR) therapy in the treatment of hematological malignancies, CAR therapy has gradually shown its advantages in the field of HIV infection. Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells. Therefore, CAR therapy may be beneficial for enhancing HIV immunity, achieving HIV control, and eliminating HIV reservoirs, gradually becoming a promising strategy for achieving a functional HIV cure. In this review, we provide an overview of the design of anti-HIV CAR proteins, the cell types of anti-HIV CAR (including CAR T cells, CAR natural killer cells, and CAR-encoding hematopoietic stem/progenitor cells), the clinical application of CAR therapy in HIV infection, and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.

Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with a range of symptoms, including palpitations, cognitive impairment, systemic embolism, and increased mortality. It places a significant burden on healthcare systems worldwide. Despite decades of research, the precise mechanisms underlying AF remain elusive. Current understanding suggests that factors like stretch-induced fibrosis, epicardial adipose tissue (EAT), chronic inflammation, autonomic nervous system (ANS) imbalances, and genetic mutations all play significant roles in its development. In recent years, the advent of wearable devices has revolutionized AF diagnosis, enabling timely detection and monitoring. However, balancing early diagnosis with efficient resource utilization presents new challenges for healthcare providers. AF management primarily focuses on stroke prevention and symptom alleviation. Patients at high risk of thromboembolism require anticoagulation therapy, and emerging pipeline drugs, particularly factor XI inhibitors, hold promise for achieving effective anticoagulation with reduced bleeding risks. The scope of indications for catheter ablation in AF has expanded significantly. Pulsed field ablation, as a novel energy source, shows potential for improving success rates while ensuring safety. This review integrates existing knowledge and ongoing research on AF pathophysiology and clinical management, with emphasis on diagnostic devices, next-generation anticoagulants, drugs targeting underlying mechanisms, and interventional therapies. It offers a comprehensive mosaic of AF, providing insights into its complexities.

Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China.

This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs. ≥100,000 copies/mL) and CD4⁺ cell count (<200 vs. ≥200 cell/µL). Median time to TND VL was assessed by Kaplan–Meier method. We also measured changes from baseline in CD4⁺ cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs).

We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND (P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) (P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) (P <0.001). No differences were seen in CD4⁺ cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) (P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain.

In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4⁺ cell count. CD4⁺ recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.

Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China.

Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People’s Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan–Meier and multivariate Cox regression analyses.

A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4⁺ T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48–5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53–5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46–9.59) were independent predictors for HBsAg seroclearance (all P <0.01).

Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness. This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness.

A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders (IRs) (CD4⁺ T-cell count >500) and immunological non-responders (INRs) (CD4⁺ T-cell count <300) was conducted. The transcriptomic profiles were used to identify distinct cell subpopulations, marker genes, and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness.

Among the cellular subpopulations analyzed, the ratios of monocytes, CD16⁺ monocytes, and exhausted B cells demonstrated the most substantial differences between INRs and IRs, with fold changes of 39.79, 11.08, and 2.71, respectively. In contrast, the CD4⁺ T cell ratio was significantly decreased (0.39-fold change) in INRs compared with that in IRs. Similarly, the ratios of natural killer cells and terminal effector CD8⁺ T cells were also lower (0.37-fold and 0.27-fold, respectively) in the INRs group. In addition to several well-characterized immune cell-specific markers, we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus (HIV) replication. Notably, ISG15, IFITM3, PLSCR1, HLA-DQB1, CCL3L1, and DDX5, which have been demonstrated to influence HIV replication through their interaction with viral proteins, emerged as significant monocyte marker genes. Furthermore, the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication.

We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs. Host genes associated with HIV replication were identified as markers of, and were found to be differentially expressed in, different types of immune cells.

Distinguishing between primary clear cell carcinoma of the liver (PCCCL) and common hepatocellular carcinoma (CHCC) through traditional inspection methods before the operation is difficult. This study aimed to establish a Faster region-based convolutional neural network (RCNN) model for the accurate differential diagnosis of PCCCL and CHCC.

In this study, we collected the data of 62 patients with PCCCL and 1079 patients with CHCC in Beijing YouAn Hospital from June 2012 to May 2020. A total of 109 patients with CHCC and 42 patients with PCCCL were randomly divided into the training validation set and the test set in a ratio of 4:1. The Faster RCNN was used for deep learning of patients’ data in the training validation set, and established a convolutional neural network model to distinguish PCCCL and CHCC. The accuracy, average precision, and the recall of the model for diagnosing PCCCL and CHCC were used to evaluate the detection performance of the Faster RCNN algorithm.

A total of 4392 images of 121 patients (1032 images of 33 patients with PCCCL and 3360 images of 88 patients with CHCC) were uesd in test set for deep learning and establishing the model, and 1072 images of 30 patients (320 images of nine patients with PCCCL and 752 images of 21 patients with CHCC) were used to test the model. The accuracy of the model for accurately diagnosing PCCCL and CHCC was 0.962 (95% confidence interval [CI]: 0.931–0.992). The average precision of the model for diagnosing PCCCL was 0.908 (95% CI: 0.823–0.993) and that for diagnosing CHCC was 0.907 (95% CI: 0.823–0.993). The recall of the model for diagnosing PCCCL was 0.951 (95% CI: 0.916–0.985) and that for diagnosing CHCC was 0.960 (95% CI: 0.854–0.962). The time to make a diagnosis using the model took an average of 4 s for each patient.

The Faster RCNN model can accurately distinguish PCCCL and CHCC. This model could be important for clinicians to make appropriate treatment plans for patients with PCCCL or CHCC.

Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.

We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs.

The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1, while those in TNENs were in MEN1, MLL2, APC, RB1, and TSC2. Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling.

We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.

Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC).

We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed Apc^Min/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays.

The abundance of fecal Veillonella parvula (V. parvula) decreased significantly after BBR administration (P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect.

BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula, thereby blocking the development of colorectal tumors.

ClinicalTrials.gov, No. NCT02226185.

With the development of combination antiretroviral therapy (cART), human immunodeficiency virus (HIV) infection has transitioned from a generally fatal disease to a manageable chronic condition over the past two decades.^[1]cART provides rapid control of HIV and partial restoration of immune function, thus preventing various HIV-related complications. However, this does not mean that people living with HIV (PLWH) completely return healthy after receiving cART. HIV-infected individuals receiving long-term cART remain at higher risk for major cardiovascular disease (CVD) than uninfected individuals.^[2]Atherosclerotic cardiovascular disease (ASCVD), which involves myocardial infarction (MI), stroke, and sudden cardiac death, is currently one of the leading causes of mortality in PLWH. Dyslipidemia is a major risk factor for CVD in PLWH, accounting for approximately 50% of the overall CVD risk.^[3]Not only there is an increased cardiovascular risk, but dyslipidemia in PLWH may also be associated with an increased risk of non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus. In addition, dyslipidemia in PLWH differs from the general population because treatment for HIV may not only induce dyslipidemia but also interact with lipid-lowering agents. Therefore, the management of dyslipidemia and CVD risk among PLWH is challenging and requires the cooperation of multidisciplinary professional teams working together to deliver appropriate care.

Human immunodeficiency virus (HIV) infection is a significant and pressing concern for public health worldwide.^[1]Midway through the 1990s, the widespread use of antiretroviral therapy (ART) has resulted in a significant paradigm shift in the management of HIV infection, thereby altering its prognosis from a life-threatening disease to a chronic and managed health condition. According to previous studies, people who are living with HIV (PLWH) that are on current ART have shown a decrease in both the morbidity and mortality associated with HIV infection, along with a decreased risk of transmitting the virus to others.^[2,3,4,5]Integrase strand transfer inhibitors (INSTIs) are the most recent category of ART medications, exhibiting strong potency, high barrier to resistance, minimal drug interactions, and excellent tolerability.^[6,7]In 2009, the Chinese Food and Drug Administration (CFDA) authorized raltegravir (RAL) for the first INSTI for the treatment of HIV/acquired immune deficiency syndrome (AIDS), followed by the approval of dolutegravir (DTG), elvitegravir (EVG), bictegravir (BIC), and cabotegravir (CAB) in 2015, 2018, 2019, and 2023, respectively. Since 2018, INSTI-based regimens have been suggested as the preferred first-line ART following the Chinese National Guidelines for HIV/AIDS Diagnosis and Treatment.^[8]However, the use of INSTIs is restricted in most regions of the Chinese mainland owing to their high cost. Therefore, >80% of PLWH in China receive free tenofovir/zidovudine + lamivudine + efavirenz under the National Free Antiretroviral Treatment Program (NFATP).^[8,9]Since the year 2020, the cost of INSTIs such as EVG, DTG, and BIC has progressively decreased and is currently covered by Chinese medical insurance. Local health insurance in major cities could cover 50-90% of the cost, providing a substantial reimbursement policy; consequently, an increasing proportion of PLWH selected INSTI-based regimens. By the end of 2022, nearly half of the PLWH in Tianjin were on INSTI-containment regimens. There has been a notable rise in the use of INSTIs, leading to the steady emergence of INSTI-related resistance mutations. Limited investigations in China indicated a relatively low level of INSTI resistance among antiretroviral-naïve PLWH in large cities, such as Beijing and Shenzhen.^[10,11]However, the prevalence of INSTI resistance among treatment-naïve individuals in Tianjin remains unknown. This study evaluated the prevalence of INSTI-associated drug resistance among ART-naïve individuals infected with HIV-1 in Tianjin, China.

To the Editor: Human immunodeficiency virus (HIV) epidemic poses a significant challenge to global public health. As of 2022, approximately 39.0 million people worldwide were living with HIV.^[1]With the ongoing evolution of combined antiretroviral therapy (cART), HIV infection has transformed into a manageable chronic disease requiring long-term treatment. Among the various classes of antiretroviral (ARV) drugs, integrase strand transfer inhibitor (INSTI)-based regimens, known for potency and tolerability, have emerged as the predominant treatment modality worldwide. The next-generation of INSTI, bictegravir (BIC), received the Food and Drug Administration (FDA) approval in 2018 as a single-tablet regimen (STR) containing BIC (50 mg)/emtricitabine (FTC, 200 mg)/tenofovir alafenamide (TAF, 25 mg) for once daily. It has been endorsed as the preferred choice for treatment-naive patients by major guidelines, including the 2021 edition of the China Acquired Immune Deficiency Syndrome (AIDS) Diagnosis and Treatment Guidelines.^[2]In China, people living with HIV (PLWH) are provided with flexible cART options, including the National Reimbursement Drug List (NRDL), self-pay drugs, and free drugs. Since being included in NRDL in 2021, BIC/FTC/TAF have gained popularity among an increasing number of patients.

To the Editor: Human immunodeficiency virus (HIV) patients have an increased risk of non-Hodgkin’s lymphoma (NHL), even in the era of antiretroviral therapy (ART).^[1]The specific mechanisms of HIV-related NHL (HIV-NHL) remain unclear. It is currently thought that HIV causes lymphoma primarily through chronic immune activation and an increased risk of infection with oncoviruses. In addition, HIV may have some other mechanisms that directly contribute to the occurrence of lymphoma.^[2]

To the Editor:Drug resistance mutations (DRMs) involving human deficiency virus type 1 (HIV-1) diminish the efficacy of current antiretroviral therapy (ART) regimens, resulting in treatment failure. A better understanding of the prevalence of local DRMs that lead to ART failure can provide valuable data for clinical- and government-level decision-making. The DRM status of people living with HIV (PLWH) refractory to ART (viral load >200 copies/mL) was assessed based on analysis of plasma samples derived from PLWH in the Sixth People’s Hospital of Zhengzhou from June 2018 to April 2022. Further, the partial polymerase (pol) and complete integrase gene-coding sequences were amplified, sequenced, and analyzed to identify DRMs. This study was approved by the Institutional Ethics Committee of the Sixth People’s Hospital of Zhengzhou (No. 2019-04). All participants signed written informed consent before sample collection.

To the Editor: Previous studies have demonstrated the efficacy of bictegravir (B), emtricitabine (F), and tenofovir alafenamide (TAF) in achieving virological suppression in human immunodeficiency virus (HIV)-infected patients. Virological suppression can be influenced by various factors, with baseline HIV-1 RNA being a critical consideration. Guidelines often use a baseline HIV RNA level of >500,000 copies/mL as the primary reference indicator for drug selection.^[1]However, previous studies on the effectiveness of B/F/TAF have not specifically analyzed patients with baseline HIV RNA >500,000 copies/mL. In Chongqing, China, where the prevalence of advanced HIV among hospitalized patients living with HIV exceeds 70%,^[2]up to 25% of patients have baseline HIV-1 RNA >500,000 copies/mL in our study, and many patients have opportunistic infections. In such a complex medical setting, the virological suppression rates of patients using B/F/TAF remain uncertain.

To the Editor:People living with the human immunodeficiency virus (PLWH) are more likely to develop cancers, have a more severe clinical course of cancers, and have a higher mortality than healthy population. Standard treatments and immunotherapy like immune-checkpoint inhibitors (ICIs) used for cancer are being employed increasingly to treat non-acquired immune deficiency syndrome-defining cancers in PLWH because of an improvement in combined antiretroviral therapy (cART) efficacy and life expectancy.^[1]Malignant tumor cells provoke suppression of immune checkpoints and promote immunosuppressive states, which favors evasion of the immune system and tumor growth. ICIs act by blocking inhibitory pathways through invigorating T cells and other innate cells and adaptive cells, thereby resulting in productive antitumor immune responses. The ICIs approved by the US Food and Drug Administration for human use include programmed cell death receptor 1 (PD-1) and programmed cell death receptor 1 ligand (PD-L1).^[2]

To the Editor: Coronavirus disease 2019 (COVID-19), instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has manifested as a formidable global pandemic, precipitating significant economic implications and leading to extensive mortalities. Simultaneously, the acquired immune deficiency syndrome (AIDS) epidemic caused by the human immunodeficiency virus (HIV) persists as a salient global health exigency. Cumulatively by the termination of 2022, AIDS-related pathologies accounted for approximately 40.4 million fatalities, with an extant global HIV population of roughly 39 million people living with HIV (PLWH), as a potentially immunocompromised population, have received limited attention in the realm of COVID-19 research. The majority of existing studies have compared HIV-treated subjects with their HIV-negative counterparts. Of the global tally of HIV cases, an estimated 9.2 million PLWH who have not received antiretroviral therapy (ART) might be at a more pronounced immunodeficiency risk than those on ART.^[1]The discrepancy in COVID-19 severity and clinical presentation between ART-experienced and ART-naïve PLWH has yet to be comprehensively understood. In light of this, our study endeavors to illuminate the distinctions in COVID-19 severity between ART-experienced and ART-naïve PLWH through a retrospective case–control analysis.

To the Editor: High-frequency resistance (typically ≥15–25% viral quasispecies) detected by conventional resistance assays has long been associated with failure of antiretroviral therapy (ART) to suppress viral replication,^[1]but the impact of pre-existing low-frequency resistance on virological response is controversial. Previous studies have shown an increased likelihood of virological response failure in patients with pre-existing low-frequency resistance mutations after initiation of antiviral therapy, especially primary ART regimens containing non-nucleoside reverse transcriptase inhibitors (NNRTIs).^[2]However, some studies have concluded differently, suggesting that pre-existing low-frequency resistance mutations do not correlate with viral response failure.^[3]This may be related to the method of detection of pre-existing low-frequency resistance mutations.

To the Editor: The epidemic of diabetes mellitus poses a major public health threat worldwide. In the United States, the prevalence of type 2 diabetes (T2D) affected 13.9% of adults and would continually increase.^[1]Diet is one of the major lifestyle risk factors for T2D, in which dietary iron has generated substantial interest over the past 20 years.^[2,3]It is to be noted that dietary vitamins A, B₂, B₆, E, C, and folic acid were reported to affect the absorption or oxidation of iron in body.^[4]However, whether these dietary vitamins play a role in iron-related T2D remains unclear. Further research revealing the holistic role of these dietary vitamins in the association between iron and T2D is needed, which would provide important guidance for decreasing the risk of iron-related T2D. The present study aimed to examine the association between dietary iron and T2D in the National Health and Nutrition Examination Survey (NHANES) and evaluate whether holistic dietary vitamins affect this relationship.

To the Editor: The incidence of diabetes complications increases with the increase in diabetes incidence. Diabetic peripheral neuropathy (DPN) is one of the most common complications in diabetes patients. DPN is very harmful and is an important cause of diabetic foot and amputation. The amputation rate of DPN patients is 10–20 times higher than that of nondiabetic patients. Every 30 s, somewhere in the world, a patient’s lower limb or part of a lower limb will be surgically amputated due to DPN.^[1]DPN seriously interferes with the physical and mental health of patients. At the same time, the high cost of treatment and rehabilitation care also causes huge economic pressure on patients. Therefore, it is particularly important to identify, diagnose, and prevent DPN in the early or ultra-early stage.

To the Editor:Hypertension is an important risk factor for the incidence and prognosis of diabetes and ischemic stroke. Both diabetes and ischemic stroke are common disorders that often occur together, and up to approximately 34% of acute ischemic stroke patients also experience diabetes.^[1]Previous studies have shown that stroke patients with hyperglycemia or diabetes exhibited increased risks of recurrent stroke, poor neurological outcomes, and mortality. However, few studies have explored the relationship between systolic blood pressure (SBP) levels or SBP trajectories and clinical outcomes in patients with both ischemic stroke and diabetes.

The authors declare that in the article "Treatments for resectable esophageal cancer: from traditional systemic therapy to immunotherapy"^[1]which was published in vol. 135, issue 18, page 2143–2156 of theChinese Medical Journal, the affiliation of the first author Yan Yan should be corrected as "Department of Thoracic Surgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China". The authors deeply apologize for any inconvenience caused.