2024年 · 第137卷第22期

Human immunodeficiency virus (HIV) is a highly adaptable and rapidly evolving virus, and the current population of people infected with HIV and diagnosed with acquired immune deficiency syndrome (AIDS) continues to grow. Although the lifespan of HIV-infected people (PWH) has been extended through control with antiretroviral therapy (ART), however, as the aging of PWH increases, this population is prone to new complications, including thromboembolic disease (TED). TED has been recognized as one of the most common cardiovascular diseases among PWH. Thrombosis often causes vascular obstruction, blood stasis, and ischemic organ damage, leading to life-threatening illness or permanent disability, which can further affect the selection and use of ART drugs in PWH. Thrombosis has become a growing problem for HIV-infected individuals, and the burden on society will continue to increase as more and more people become infected. Therefore, we conclude the latest progress about causative factors and therapeutic interventions of HIV/TED to provide new ideas for in-depth clinical research and further optimize appropriate treatment options.

Transplant oncology refers to the implementation of transplant surgery in cancer treatment, with the core understanding of replacing diseased organs with healthy ones to solve cancer fundamentally. Early in 2004, dermatologic surgeons presented "transplant oncology", originally referring tode novomalignancies (DNMs) of skin after organ transplantation.^[1]The precise conceptualization of transplant oncology was initially established by Hibiet al^[2]in 2014, encompassing the triple distresses (oncological, immunological, and technical) and highlighting organ bioengineering and regenerative medicine as the ultimate solution to these challenges. Sapisochinet al^[3]outlined the recent progresses and summarized evolution, elucidation, exploration, and extension as "the four E" pillars of transplant oncology. Currently, over 250,000 literatures have been published regarding transplant oncology, with the research scope extending beyond surgery and encompassing oncology, immunology, and other associated disciplines. Notably, owing to superior clinical outcomes of liver transplantations (LTs) for hepatobiliary malignancies, the evolving field of transplant oncology predominantly concentrates on the liver transplant oncology. However, balancing potential clinical benefits and donor liver scarcity remains the primary concern. Therefore, the current clinical challenges in liver transplant oncology can be summarized and categorized into the following five facets: optimal candidate selection criteria, pre-transplant oncological management, intra-transplant reasonable surgical procedures, individualized immunosuppressive regimen, and clinical strategies for tumor recurrences and DNMs.

The Acquired Immunodeficiency Syndrome Professional Group of the Society of Infectious Diseases of the Chinese Medical Association formulated the first edition of the Chinese Guidelines for the Diagnosis and Treatment of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (referred to as the Guidelines) in 2005. The 2024 edition of the Guidelines has been compiled by updating the 2021 fifth edition, incorporating the latest research advancements in antiviral therapy, comprehensive management, opportunistic infections, concurrent tumors, and the prevention and intervention of HIV infection. The new edition also introduces a new section on "Incomplete immune reconstitution", proposes the concept of "HIV vulnerable populations" for the first time with recommendations for their diagnosis and treatment. This edition of the Guidelines covers 14 sections: epidemiology, pathogenic characteristics, laboratory tests, pathogenesis, clinical presentation and staging, diagnostic criteria, common opportunistic infections, antiretroviral therapy, immune reconstitution inflammatory syndrome, incomplete immune reconstitution, AIDS-related neoplasms, prevention of mother-to-child transmission and conception in serodiscordant couples, pre- and post-exposure prophylaxis, and whole-course management of HIV infection. This edition of the Guidelines aims to assist clinical physicians in making informed decisions in the diagnosis, treatment, and management of HIV/AIDS and will be periodically revised and updated based on domestic and international research progress.

What are the recommendations for the timing, dosage, and usage of corticosteroids during cytokine release syndrome (CRS) caused by chimeric antigen receptor (CAR)-T cell therapy for hematologic malignancies?

Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) is an advanced neuromodulation technique that leverages the power of magnetic resonance imaging (MRI) for guidance and temperature monitoring and focused ultrasound waves to perform noninvasive brain modulation.^[1]This revolutionary method opens new avenues for treating various brain disorders, including essential tremor (ET), Parkinson’s disease (PD), and some psychiatric conditions, without requiring open surgery.^[2,3,4]However, there is a lack of consensus on standardized protocols, particularly those tailored to Asian demographics. To promote the standardized application of MRgFUS and to facilitate informed decision-making in clinical practice, specialists in the field collaborated to establish a comprehensive consensus following extensive discussions. The consensus centers on the ExAblate Neuro devices (InSightec, Tirat Carmel, Israel) because these devices are currently the only Food and Drug Administration (FDA)-approved focused ultrasound (FUS) system for brain thermoablation, and the majority of accumulated clinical expertise in the field largely stems from their utilization. This consensus comprehensively elucidates indications, contraindications, procedures, and clinical management. The recommendations inTable 1aim to enhance MRgFUS-centered patient care and clinical protocols. The full-length version of the consensus is shown in the Supplementary Materials, http://links.lww.com/CM9/C153.

Metabolic dysfunction-associated steatotic liver disease (MASLD), also called non-alcoholic fatty liver disease, is the most epidemic chronic liver disease worldwide. Metabolic dysfunction-associated steatohepatitis (MASH) is the critical stage of MASLD, and early diagnosis and treatment of MASH are crucial for reducing the incidence of intrahepatic and extrahepatic complications. So far, pharmacotherapeutics for the treatment of MASH are still a major challenge, because of the complexity of the pathogenesis and heterogeneity of MASH. Many agents under investigation have shown impressive therapeutic effects by targeting different key pathways, including the attenuation of steatohepatitis or fibrosis or both. It is notable that thyroid hormone receptor-β agonist, resmetirom has become the first officially approved drug for treating MASH with fibrosis. Other agents such as peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 analogs, and fibroblast growth factor 21 analogs are awaiting approval. This review focuses on the current status of drug therapy for MASH and summarizes the latest results of new medications that have completed phase 2 or 3 clinical trials, and presents the future directions and difficulties of new drug research for MASH.

Leukocyte immunoglobulin-like receptor (LILR) B4 (also known as ILT3/CD85k) is an immune checkpoint protein that is highly expressed in solid tumors and hematological malignancies and plays a significant role in the pathophysiology of cancer. LILRB4 is highly expressed in acute myeloid leukemia (AML), and this phenotype is associated with adverse patient outcomes. Its differential expression in tumors compared to normal tissues, its presence in tumor stem cells, and its multifaceted roles in tumorigenesis position it as a promising therapeutic target in AML. Currently, several immunotherapies targeting LILRB4 are undergoing clinical trials. This review summarizes advancements made in the study of LILRB4 in AML, focusing on its structure, ligands, expression, and significance in normal tissues and AML; its protumorigenic effects and mechanisms in AML; and the application of LILRB4-targeted therapies in AML. These insights highlight the potential advantages of LILRB4 as an immunotherapeutic target in the context of AML.

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.

We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.

At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively (P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence (P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880).

Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Rapid initiation of antiretroviral therapy (ART) is recommended by guidelines, however, real-world studies of same-day initiation of ART in China are limited, and an optimal treatment regimen has yet to be identified. The study aims to provide a realistic reference for rapid initiation of ART.

We retrospectively analyzed the clinical data of treatment-naïve people with human immunodeficiency virus (PWHs) who were diagnosed and prescribed same-day ART initiation from January 1, 2021 to December 31, 2022 at Chongqing Public Health Medical Center. PWHs voluntarily chose an ART regimen that divided them into two groups: National Free Antiretroviral Treatment Program (NFATP)-recommended regimens group (2 nucleoside reverse transcriptase inhibitors + non-nucleoside reverse transcriptase inhibitors/protease inhibitors) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) group. The primary endpoint was the virological outcome of the two groups for same-day ART initiation at 24 weeks and 48 weeks. The secondary endpoints included changes in CD4 counts, maintenance of the original ART regimen at 48 weeks, and lipid levels and renal function at 48 weeks.

A total of 255 PWHs were included in the study, including 131 (51.4%) in the NFATP group and 124 (48.6%) in the BIC/FTC/TAF group. The overall virological suppression rates at 24 weeks and 48 weeks were 78.2% (165/211) and 95.4% (207/217), respectively. At 24 weeks, the virologic suppression rate in the NFATP group was lower than that in the BIC/FTC/TAF group (65.3% [66/101] vs. 90.0% [99/110], P <0.001). The median increase in the CD4 count was 198.0 (126.0-300.0) cells/µL at 24 weeks, with 182.0 (108.0-245.0) cells/µL in the NFATP group and 219 (132.0-316.0) cells/µL in the BIC/FTC/TAF group (P = 0.035). At 48 weeks, there was no significant difference in the virological suppression rate or CD4 count between the groups. The 48-week initial ART regimen retention rates and treatment retention rates were significantly higher in the BIC/FTC/TAF group than in the NFATP group (91.1% (113/124) vs. 71.8% (94/131), 99.2% (118/119) vs. 93.0% (120/129), respectively). In terms of safety, there were no significant changes from baseline in levels of creatinine, estimated glomerular filtration rate (eGFR), or lipids in either group at 48 weeks.

ART initiation on the day of diagnosis is effective, safe, and feasible, with satisfactory rates of virologic suppression, 48-week initial ART regimen retention rates, and treatment retention rates in treatment-naïve PWHs. In our study, the early virologic suppression rate, CD4 cell counts, and treatment retention of the BIC/FTC/TAF regimens were significantly better than those of the NFATP regimens.

Substantial progress in air pollution control has brought considerable health benefits in China, but little is known about the spatio-temporal trends of economic burden from air pollution. This study aimed to explore their spatio-temporal features of disease burden from air pollution in China to provide policy recommendations for efficiently reducing the air pollution and related disease burden in an era of a growing economy.

Using the Global Burden of Disease method and willingness to pay method, we estimated fine particulate matter (PM_2.5) and/or ozone (O₃) related premature mortality and its economic burden across China, and explored their spatio-temporal trends between 2005 and 2017.

In 2017, we estimated that the premature mortality and economic burden related to the two pollutants were RMB 0.94 million (68.49 per 100,000) and 1170.31 billion yuan (1.41% of the national gross domestic product [GDP]), respectively. From 2005 to 2017, the total premature mortality was decreasing with the air quality improvement, but the economic burden was increasing along with the economic growth. And the economic growth has contributed more to the growth of economic costs than the economic burden decrease brought by the air quality improvement. The premature mortality and economic burden from O₃ in the total loss from the two pollutants was substantially lower than that of PM_2.5, but it was rapidly growing. The O₃-contribution was highest in the Yangtze River Delta region, the Fen-Wei Plain region, and some western regions. The proportion of economic burden from PM_2.5 and O₃ to GDP significantly declined from 2005 to 2017 and showed a decreasing trend pattern from northeast to southwest.

The disease burden from O₃ is lower than that of PM_2.5, the O₃-contribution has a significantly increasing trend with the growth of economy and O₃ concentration.

T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.

Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.

The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4⁺ T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8⁺ T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8⁺ T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F.

Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Scleroderma is characterized by inflammation and fibrosis, predominantly occurring in the skin and extending to various parts of the body. The pathophysiology of scleroderma is multifaceted, with the current understanding including endothelial damage, inflammatory cell infiltration, and fibroblast activation in its progression. Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma’s pathogenesis.

In this study, we administered bleomycin intradermally to the dorsal skin of four individual murine models. Subsequently, skin tissues were harvested at predetermined intervals for comprehensive spatial transcriptomic analysis to determine the spatial dynamics influencing scleroderma pathogenesis. To validate the possible results from bioinformatic analysis, further in vitro and in vivo experiments were conducted.

Analysis of the spatial transcriptome revealed significant alterations in cell clusters during the progression of scleroderma. Gene Ontology analysis identified disruptions in lipid metabolism as the disease advanced. Pseudotime analysis provided evidence for a phenotypic transition from adipocytes to fibroblasts. In vitro studies demonstrated increased expression of Col1a1 and α-SMA as the disease progressed. These fibroblasts have been identified as key contributors to the increasing inflammation. Co-culturing TGF-β induced adipocytes with RAW264.7 cells resulted in overexpression of pro-inflammatory cytokines in the RAW264.7 cells. Both in vitro and in vivo experiments confirmed adipocyte loss and fibroblast formation, with transformed fibroblasts showing pronounced pro-inflammatory characteristics, highlighting their crucial role in the disease mechanism.

Our study showed the spatial distribution and dynamic alterations of various cell types during scleroderma progression. Crucially, we identified the transformation of adipocytes into fibroblasts as a key factor promoting disease advancement. These emergent fibroblasts intensify inflammation, indicating that research on these cell clusters could reveal key scleroderma mechanisms and guide future therapies.

To the Editor:China provides free antiretroviral therapy (ART) for people with human immunodeficiency virus (HIV), typically using two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI). This regimen has significantly reduced mortality and slowed HIV spread over the past 20 years.^[1,2]However, it has a low barrier to resistance, making drug resistance mutations (DRMs) a significant challenge. Following virological failure with a regimen of tenofovir (TFV), lamivudine or emtricitabine (3TC or FTC), and an NNRTI (efavirenz or nevirapine), DRMs to 3TC/FTC or TFV are common.^[3]Despite this, 3TC/FTC and TFV are still included in many single-tablet regimens (STRs), raising concerns about their effectiveness following first-line ART failure. Bictegravir, a second-generation integrase strand transfer inhibitors (INSTIs) co-formulated with FTC and TFV alafenamide (B/F/TAF), offers effective viral suppression, minimal drug interactions, high resistance barriers, and excellent tolerability.^[4]B/F/TAF is recommended as a preferred regimen for both initial treatment and switching in people with HIV (PWH).^[2,5]While data suggest B/F/TAF is effective in virologically suppressed patients with historical DRMs, the available data are limited and retrospective.^[6,7,8]

To the Editor: Tuberculosis (TB) is the leading cause of death in people living with HIV (PLWH) globally. Given the increased risk of TB infection, TB preventive therapy (TPT) is recommended for PLWH to prevent TB activation and to reduce relevant mortality. However, the implementation of TPT remains weak with only 21% of eligible PLWH initiated on TPT globally in 2021,^[1]primarily due to the implementation challenges in developing countries. The low completion rate of TPT may be attributed to various reasons, including socio-economic factors, individual behaviors (medication adherence, lack of knowledge, etc.), unstable supply chain of anti-TB drugs, and insufficient understanding of TB treatment guidelines. China has always been regarded as a region with high TB burden. Therefore, conditional TB prophylaxis has been recommended in national guidelines for HIV-infected patients since 2006, with emphasis on those with CD4⁺T count <200 cells/µL, or those with positive tests of latent TB screening, preferred using interferon γ release assay (IGRA). Since 2021, universal TB prophylaxis strategy has been recommended following the World Health Organization (WHO) guidelines. However, in real practice, HIV-infected individuals seldomly receive universal TPT when initiating antiretroviral therapy (ART) in most centers. Nevertheless, there is little report on the incidence of active TB development following ART initiation of HIV-infected individuals in China. In addition, whether a universal prophylaxis strategy would benefit the population also depends on the population-based prevalence of TB activation, as well as therapeutic cost and drug-related adverse events. Therefore, we here aim to compile the prevalence of active TB of PLWH in the first five years of initiating ART in one comprehensive referring center in Beijing China, providing real-world data for a more individualized TPT in HIV-infected individuals.

To the Editor: Carotid artery stenting (CAS) is a key treatment of extracranial internal carotid artery (EICA) stenosis for secondary stroke prevention. Hypotension is a common perioperative event concerning balloon dilation of the carotid sinus and can lead to serious adverse events, such as ischemic stroke, myocardial infarction, and prolonged length of stay (LOS).^[1]The previous study^[2]reviewed several factors related to post-CAS hypotension, such as older age,coronary artery disease,left atrial volume, and plaque location but these are not readily modifiable. Catecholamine plays an important role in maintaining blood pressure (BP) after CAS or carotid endarterectomy (CEA); a previous study showed that after CEA, catecholamine increased with increasing BP while after CAS, a decrease in BP followed by non-significant changes in catecholamine levels.^[3]As studies have shown renin-angiotensin-aldosterone system inhibitor (RASI) drugs block the release of catecholamine, they may be effective in preventing post-CAS hypotension. We aimed to determine the relationship between RASI use and persistent post-CAS hypotension and their relation to changes in catecholamine levels.

To the Editor: Renal cell carcinoma is the most common cancer of the genitourinary tract and leads to over 170,000 deaths annually worldwide. For localized tumors, robot-assisted partial nephrectomy (RAPN) has emerged as a popular option due to its numerous benefits, including better ergonomics, better functional outcomes, similar oncological outcomes, and minimal invasiveness. The KangDuo surgical robot (KD-SR), a novel robotic surgical platform, was developed by SuZhou KangDuo Robot Co., Ltd. (Suzhou, China). Recently, we reported that the KD-SR achieved noninferior outcomes compared to the da Vinci Si Surgical System (DV-SS-Si) in terms of surgical success for T1a tumors.^[1]However, the oncological outcomes of the KD-SR and the DV-SS-Si are yet to be compared. In this prospective randomized cohort trial, we aimed to compare the patient-reported health-related quality of life (HRQoL) and medium-term oncological outcomes of the KD-SRvs. the DV-SS-Si for RAPN.

To the Editor: Posterior fossa group A (PFA) ependymoma is one of the most common and aggressive pediatric tumors, which currently lacks effective chemotherapies.^[1,2]Previously, we revealed CXorf67, which is specially unregulated in PFA ependymoma, as a negative regulator of DNA homologous recombination (HR) repair, rendered PFA tumors highly sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors combined with radiotherapy through a mechanism of synthetic lethality.^[3]However, PFA ependymoma mostly occurs in infants and young children, to whom ionizing radiation may pose great risks. Therefore, there is still an urgent need in the treatment of PFA ependymoma patients who could not or are reluctant to receive radiotherapy. Given that platinum-based drugs (cisplatin and carboplatin), as DNA damaging agents, are widely used as anticancer drugs. This study aimed to investigate whether the combination of PARP inhibitors and DNA-damaging chemotherapy could efficiently kill CXorf67-expressing tumor cells.

The authors declare that in the article published in vol. 137, issue 18 of the Chinese Medical Journal,^[1]an error was identified in the Introduction section "These cancers accounted for nearly 3.6 million new cases and 1.2 million deaths globally." should be corrected to "These cancers accounted for nearly 3.77 million new cases and 1.35 million deaths globally." The error does not affect the results and conclusions of the article. The authors deeply apologize for any inconvenience caused.