2024年 · 第137卷第12期

Neoadjuvant therapy can yield clinical benefits in early-stage breast cancer with indications. The indications, treatment regimens, and efficacy of neoadjuvant therapy have been investigated, which have contributed valuable clinical evidence.^[1,2]The Chinese Society of Breast Surgery convened a panel of breast disease experts to review and discuss the literature on neoadjuvant therapy for breast cancer and evaluate relevant evidence by referring to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Taking into account China’s specific circumstances, the society and participating experts developed theClinical Practice Guidelines for Neoadjuvant Therapy for Early-stage Breast Cancer (Version 2022)to serve as a reference for breast surgeons in China.

Cancer is a major global health issue. Effective therapeutic strategies can prolong patients’ survival and reduce the costs of treatment. Drug repurposing, which identifies new therapeutic uses for approved drugs, is a promising approach with the advantages of reducing research costs, shortening development time, and increasing efficiency and safety. Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug used to treat chronic alcoholism, has a great potential as an anticancer drug by targeting diverse human malignancies. Several studies show the antitumor effects of DSF, particularly the combination of DSF and copper (DSF/Cu), on a wide range of cancers such as glioblastoma (GBM), breast cancer, liver cancer, pancreatic cancer, and melanoma. In this review, we summarize the antitumor mechanisms of DSF/Cu, including induction of intracellular reactive oxygen species (ROS) and various cell death signaling pathways, and inhibition of proteasome activity, as well as inhibition of nuclear factor-kappa B (NF-κB) signaling. Furthermore, we highlight the ability of DSF/Cu to target cancer stem cells (CSCs), which provides a new approach to prevent tumor recurrence and metastasis. Strikingly, DSF/Cu inhibits several molecular targets associated with drug resistance, and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant patients. Studies of DSF/Cu may shed light on its improved application to clinical tumor treatment.

Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal–fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal–fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal–fetal tolerance based on maternal–fetal crosstalk. Insights into maternal–fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.

Given the recent updates in cancer burden estimates by GLOBOCAN 2022, this study was undertaken to provide pertinent perspectives within the context of the Human Development Index (HDI) and major world economies.

Datasets sourced from GLOBOCAN encompassed cancer cases and deaths across all cancer types in 2022, alongside projections up to 2050. Cancer incidences and deaths of the top 10 cancers within China and four distinct HDI-classified regions were compared using descriptive analyses. Age-standardized incidence rates (ASIRs) and mortality rates (ASMRs) worldwide for the most prevalent cancers in 2022 across ten largest economies and four-tier HDIs were examined. The top five cancer types concerning both incidence and mortality in China were delineated by sex and age group.

In males, prostate cancer predominated in countries with low, high (except China), and very high HDI. Prostate and liver cancers were prominent causes of death in countries with low HDI. In females, breast and cervical cancers predominated in countries with low-to-medium HDI. Lung and colorectal cancer incidence and deaths increased with high HDI for both sexes. ASIRs and ASMRs for breast, prostate, lung, and colorectal cancers in the top 10 economies were higher than the global average. However, liver, stomach, and cervical cancers in most Western countries exhibited lower rates. In China, hematologic malignancies (43%) were prevalent among children aged 0–14 years, whereas thyroid cancer led among adolescents and young adults aged 15–39 years. Regarding incidence and mortality, lung cancer predominated for individuals over 40 years, except for females aged 40–59 years, in whom breast cancer predominated. Projected trends indicated substantial increases in new cancer cases (76.6%) and deaths (89.7%) over the next three decades.

Infection- and poverty-related cancer burdens are offset by increased prostate, breast, colorectal, and lung cancer incidence associated with rapid societal and economic transitions. Cancer incidence and mortality patterns in China feature characteristics of developed and developing countries, necessitating tailored, evidence-based, and comprehensive strategies for effective cancer prevention and control.

Hepatitis B virus (HBV) infection is the primary cause of hepatocellular carcinoma (HCC) in China. The target population for HCC screening comprises individuals who test positive for hepatitis B surface antigen (HBsAg). However, current data on the prevalence of HBV infection among individuals who are eligible for HCC screening in China are lacking. We aimed to assess the seroepidemiology of HBV infection among Chinese individuals eligible for HCC screening to provide the latest evidence for appropriate HCC screening strategies in China.

Questionnaires including information of sex, age, ethnicity, marital status, educational level, source of drinking water, as well as smoking and alcohol consumption history and serum samples were collected from females aged 45–64 years and males aged 35–64 years in 21 counties from 4 provinces in eastern and central China between 2015 and 2023. Enzyme-linked immunosorbent assay methods were used to detect the serum HBV marker HBsAg.

A total of 603,082 individuals were enrolled, and serum samples were collected for analysis from January 1, 2015 to December 31, 2023. The prevalence of HBsAg positive in the study population was 5.23% (31,528/603,082). The prevalence of HBsAg positive was greater in males than in females (5.60% [17,660/315,183] vs 4.82% [13,868/287,899], χ² = 187.52, P <0.0001). The elderly participants exhibited a greater prevalence of HBV infection than younger participants (χ² = 41.73, P <0.0001). Birth cohort analysis revealed an overall downward trend in HBV prevalence for both males and females. Individuals born in more recent cohorts exhibited a lower prevalence of HBV infection as compared to those born earlier.

The current prevalence of HBV infection remains above 5% in populations eligible for HCC screening in China.

Further efforts should be made to increase the accessibility of HCC screening among individuals with HBV infection.

Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging).

This prospective trial included patients with initial pre-NAC cT1–3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated.

A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30).

In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%.

chictr.org.cn, ChiCTR2100049093

Intrauterine valvuloplasty is an innovative therapy, which promotes ventricular growth and function in some congenital heart diseases (CHDs). The technique remains challenging and can only be performed in a few centers. This study aimed to assess the feasibility and mid-term outcomes of fetal cardiac intervention (FCI) in fetuses with critical CHD in an experienced tertiary center.

Five fetal aortic valvuloplasty (FAV) or fetal pulmonary valvuloplasty (FPV) procedures were performed in our fetal heart center between August 2018 and May 2022. Technical success was defined as crossing the aortic or pulmonary valve and balloon inflation, followed by evidence of increased blood flow across the valve and/or new regurgitation. Follow-up clinical records and echocardiography were obtained during the prenatal and postnatal periods.

Five fetuses received FAV or FPV, including critical aortic stenosis (n = 2) and pulmonary atresia with intact ventricular septum (n = 3). The mean maternal age was 33.0 ± 2.6 years. The median gestational age (GA) at diagnosis was 24 weeks (range, 22-26 weeks). The median GA at intervention was 29 weeks (range, 28-32 weeks). All five cases underwent successful or partially successful procedures. One patient had pulmonary valve perforation without balloon dilation. No procedure-related deaths or significant complications occurred. However, one neonatal death occurred due to heart and renal failure. The median follow-up period was 29.5 months (range, 8.0-48.0 months). The four surviving patients had achieved biventricular circulation, exhibited improved valve, and ventricular development at the last follow-up visit.

Intrauterine FCI could be performed safely with good prognosis in critical CHD.

Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.

This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle.

The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ² = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ² = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ² = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models.

Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.

ClinicalTrials.gov, No. NCT03075280.

Antiretroviral therapy (ART) was often associated with dyslipidemia among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) or lamivudine, efavirenz, and tenofovir disoproxil fumarate (3TC+EFV+TDF), monitoring at weeks 4, 12, 24, and 48.

A case-control retrospective study was conducted. The newly diagnosed HIV-infected individuals attending the sexual transmission disease (STD)/AIDS clinic of Beijing Youan Hospital, Capital Medical University, from January to December 2021. The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at different time points over 48 weeks between two groups were compared. A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C.

A total of 870 participants, with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group. There were no statistically significant differences in median age, baseline CD4/CD8 ratio, median body mass index (BMI) between the two groups. In both two groups, levels of TG, TC, and LDL-C were higher at 4 weeks, 12 weeks, and 24 weeks of treatment (all P <0.05), and there were no statistically significant differences at 48 weeks compared to those at baseline (all P >0.05). In addition, the differences in average changes of the level of TG, TC, HDL-C, and LDL-C from weeks 4, 12, 24, and 48 to baseline between two groups were not statistically significant (all P >0.05). Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA ≥10⁵ copies/mL (compared with <10⁵ copies/mL) was associated with an increased risk of elevated LDL-C (hazard ratio = 1.26, 95% confidence interval: 1.07-1.48, P = 0.005).

Transient elevations in blood lipid levels (TC, TG, HDL-C, and LDL-C) were observed in treatment-naïve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks, 12 weeks, and 24 weeks of treatment. However, these levels did not differ significantly from baseline after 48 weeks of treatment, regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.

Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.

Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation.

HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days (P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4⁺ and CD8⁺ T cells in the spleen (P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes (CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes (CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4⁺ Foxp3⁺ cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs.

HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

To the Editor:Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show significant efficacy in patients with advanced-stage non-small cell lung cancer (NSCLC) with sensitiveEGFRmutations and significantly prolong the survival of these patients. However, drug resistance emerges in most patients. Previous studies indicated that cyclin-dependent kinase 4/6 (CDK4/6) gene amplification was one of the resistance mechanisms of the EGFR-TKI osimertinib, weakening its efficacy. Treatment options forEGFR-mutant NSCLC patients withCDK4amplification are limited to add CDK4 inhibitors.

To the Editor:With the wide application of next-generation sequencing (NGS), a number ofEML4-ALKfusion partners or coexisting (non)-EML4-ALKand non-EML4-ALKhave been detected in non-small cell lung cancer (NSCLC). Although targeted therapies for patients with metastatic NSCLC and actionable mutations dramatically change how these patients are treated, studies have demonstrated differences in progression-free survival (PFS) among patients based on differentALKfusion partners.^[1]

To the Editor: The colorectal cancer (CRC) is the fourthmost common cause of cancer deaths in China that was treated as a public health threat, accounting for approximately 10% of all the cancer-caused mortalities each year.^[1]It usually takes decades to develop from a polyp to full CRC,^[2]which allows a time window for detecting precancerous lesions and taking early steps for preventions and treatments.

To the Editor:Malignant ovarian tumors during pregnancy (MOTP) rank second after cervical cancer among gynecological malignancies diagnosed during pregnancy, and most women today hope to maintain pregnancy and preserve fertility, which complicates oncologic treatment, as all potential complications and prognoses should be carefully considered for both the mother and fetus. A coordinated approach from a multidisciplinary team involving gynecological oncologists, obstetricians, and pathologists is recommended, and each patient should be managed individually based on several important factors, including gestational week (GW) at initial diagnosis, histologic type, International Federation of Gynecology and Obstetrics (FIGO) stage, and patient preference whether to terminate pregnancy or not. Surgical intervention and chemotherapy administration should be carefully performed in cases where pregnancy is maintained. The therapeutic effects on the tumor and the potential harmful events to the fetus should be appropriately balanced. Although prior studies have shown that the prognosis of such malignancies is similar to that in the non-pregnant state, the result should be interpreted cautiously, as the sample size in these studies was not large enough to control for all prognostic factors.^[1]Herein, we evaluated the current management strategies for MOTP with emphasis on the balance between mother and fetal health and oncologic and obstetric outcomes.

To the Editor: Pelvic organ prolapse (POP) is a common pelvic floor disorder in older women and is responsible for a significant decrease in health-related quality of life. With the increased longevity of women, POP is becoming a major health concern.^[1]Laparoscopic sacrocolpopexy (LSC) is a common mesh-based surgical approach for severe prolapse, and a high cure rate and few complications have been reported.^[2]To our knowledge, the long-term durability, complications, and pelvic floor symptoms after LSC have not been fully evaluated in detail. A few studies assessed the 5-year outcome after LSC, but these reports were limited by their retrospective design, uneven follow-up time, or inconsistent outcome assessment.

To the Editor: Chronic urticaria, prevalent globally and increasing in China, predominantly affects young and middle-aged women, impacting their quality of life (QoL).^[1]Standard treatment involves second-generation H1 antihistamines, with bilastine showing promise due to its selective action and minimal side effects. However, direct comparative studies are scarce, particularly in the Chinese population. We aimed to evaluate the efficacy and safety of bilastine compared to levocetirizine in Chinese patients.

To the Editor:Alzheimer’s disease (AD) is an irreversible chronic neurodegenerative disease. AD initially affects short-term memory, thinking, and behavior. It then severely disrupts the normal lives of patients and their families and may eventually lead to death. Mild cognitive impairment (MCI) is considered an early stage of AD. Some studies have shown that nearly 20% of patients with MCI are at a risk of developing AD within the next four years.^[1]Although there is no impressive way to stop the further development of MCI, only a series of procedures can slow it. Thus, timely and accurate intervention is essential to effectively slow the disease progression.

To the Editor:Recent studies have characterized drug-resistant epilepsy (DRE) as essentially a neural network disease.^[1]Detection and disconnection of this pathological epileptic connectome or network can greatly improve seizure outcomes. Our team also proposes the development of the newly emerging branch of epileptic networks neurosurgery (ENN). Responsive neurostimulation (RNS) is an ENN-oriented emerging treatment option without the resection of the seizure-onset zone or epileptic focus and aims to control the seizure or other epileptic manifestations by modulating or disrupting the network’s key nodes (epileptic hubs) in a self-responsive way. In 2013, the NeuroPace-RNS System received US Food and Drug Administration approval for adult patients with medically refractory focal onset seizures. However, the NeuroPace system is mainly utilized in the US and European countries and is currently unavailable in China. Here, we adopted the novel RNS system that was completely developed by a Chinese team and have performed the first-in-man (FIM) study. The purpose of this study was to demonstrate that it is a safe and effective RNS system for DRE patients. The study was registered with the Chinese Clinical Trial Registry (www.chictr.org.cn; ChiCTR2200055247), and was approved by the institutional review board at each participating center with written informed consent.

To the Editor: The shortage of deceased donor (DD) kidneys for transplantation remains a persistent concern. Despite the potential reversibility of acute kidney injury (AKI) lesions, kidneys from pediatric donors with AKI are often underutilized, especially in the context of pediatric transplantation. By implementing single kidney transplantation (SKT) from pediatric donors to pediatric recipients (PTP), we can optimize the utilization of available kidneys and increase the number of pediatric recipients.

To the Editor: The primary cause of end-stage kidney disease (ESKD) in China is chronic glomerulonephritis (GN), which accounts for 45% of ESKD patients.^[1]There is currently no nationwide large-scale study on the long-term prognosis of kidney transplantation in patients with chronic GN in China. Over the past decade, however, few landmark studies from populations in Europe^[2,3]and the United States^[4]have provided important reference data for this issue. Therefore, we propose to conduct a nationwide multicenter retrospective study, which was launched by the National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, from 2017 to 2020, to retrospectively analyze and collect the clinical prognosis characteristics of different chronic GN patients in China after kidney transplantation, laying the foundation for describing disease outcomes, exploring relevant risk factors, guiding clinical decision-making, and improving the long-term prognosis of kidney transplant patients in China. This research project was reviewed and approved by the Institutional Research Ethics Committee of Jinling Hospital, Nanjing University School of Medicine (No. 2017NZKYKS-002-01) and was conducted according to the principles of theDeclaration of Helsinki. Written informed consent was obtained from all participants.