2024年 · 第137卷第12期

新辅助治疗可在有适应症的早期乳腺癌中产生临床益处。对新辅助治疗的适应证、治疗方案、疗效进行了研究，贡献了有价值的临床证据。^[1,2]中国乳腺外科学会召集乳腺疾病专家小组对乳腺癌新辅助治疗文献进行回顾和讨论，并参考推荐、评估、开发和评价分级（GRADE）系统对相关证据进行评估。学会和与会专家结合中国的具体情况，制定了早期乳腺癌新辅助治疗临床实践指南（2022版）为我国乳腺外科医生提供参考。

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.

致编辑：表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）在敏感的晚期非小细胞肺癌（NSCLC）患者中显示出显著的疗效EGFR突变，并显著延长这些患者的生存期。然而，大多数患者会出现耐药性。先前的研究表明细胞周期蛋白依赖性激酶4/6（CDK4/6）基因扩增是EGFR-TKI奥希替尼的耐药机制之一，削弱了其疗效。治疗方案EGFR-突变型非小细胞肺癌患者CDK4扩增仅限于添加CDK4抑制剂。

致编辑：随着下一代测序（NGS）的广泛应用，许多EML4-ALK融合伙伴或共存（非）-EML4-ALK和非-EML4-ALK已在非小细胞肺癌(NSCLC)中检测到。尽管针对转移性非小细胞肺癌和可操作突变患者的靶向治疗极大地改变了这些患者的治疗方式，但研究表明，基于不同的治疗方法，患者的无进展生存期(PFS)存在差异ALK融合伙伴。^[1]

致编辑：结直肠癌（CRC）是中国癌症死亡的第四大常见原因，被视为公共健康威胁，每年约占所有癌症死亡人数的10%。^[1]从息肉发展到完全结直肠癌通常需要几十年的时间，^[2]其允许用于检测癌前病变并采取早期步骤进行预防和治疗的时间窗。

致编辑：在妊娠期诊断的妇科恶性肿瘤中，妊娠期恶性卵巢肿瘤（MOTP）仅次于宫颈癌排名第二，当今大多数妇女希望维持妊娠和保留生育能力，这使肿瘤治疗复杂化，因为应仔细考虑母亲和胎儿的所有潜在并发症和预后。建议由妇科肿瘤学家、产科医生和病理学家组成的多学科团队采取协调方法，应根据几个重要因素对每位患者进行单独管理，包括初始诊断时的孕周（GW）、组织学类型、国际妇产科联合会（FIGO）分期以及患者是否终止妊娠的偏好。在维持妊娠的情况下，应谨慎进行手术干预和化疗。对肿瘤的治疗效果和对胎儿的潜在有害事件应适当平衡。尽管先前的研究表明此类恶性肿瘤的预后与非妊娠状态相似，但应谨慎解释结果，因为这些研究中的样本量不足以控制所有预后因素。^[1]在此，我们评估了当前MOTP的管理策略，重点是母亲和胎儿健康以及肿瘤和产科结局之间的平衡。

致编辑：盆腔器官脱垂（POP）是老年妇女常见的盆底疾病，是健康相关生活质量显著下降的原因。随着女性寿命的延长，持久性有机污染物正成为一个主要的健康问题。^[1]腹腔镜骶阴道固定术（LSC）是治疗严重脱垂的常见网片手术方法，治愈率高，并发症少。^[2]据我们所知，LSC术后的长期持久性、并发症和盆底症状尚未得到充分详细评估。少数研究评估了LSC后的5年结局，但这些报告受到其回顾性设计、不均匀的随访时间或不一致的结局评估的限制。

致编辑：慢性荨麻疹在全球流行，在中国呈上升趋势，主要影响中青年女性，影响她们的生活质量（QoL）。^[1]标准治疗涉及第二代H1抗组胺药，比拉斯汀因其选择性作用和最小的副作用而显示出前景。然而，直接的比较研究很少，尤其是在中国人群中。我们旨在评价比拉斯汀与左西替利嗪在中国患者中的疗效和安全性。

致编辑：阿尔茨海默病（AD）是一种不可逆的慢性神经退行性疾病。AD最初影响短期记忆、思维和行为。然后严重扰乱患者及其家人的正常生活，最终可能导致死亡。轻度认知障碍（MCI）被认为是AD的早期阶段。一些研究表明，近20%的MCI患者在未来四年内有发展为AD的风险。^[1]虽然没有令人印象深刻的方法来阻止MCI的进一步发展，但只有一系列的程序可以减缓它。因此，及时和准确的干预对于有效减缓疾病进展至关重要。

致编辑：最近的研究将耐药性癫痫（DRE）描述为本质上是一种神经网络疾病。^[1]检测和断开这种病理性癫痫连接体或网络可以极大地改善癫痫发作结果。我们的团队还提议发展癫痫网络神经外科（ENN）的新兴分支。反应性神经刺激（RNS）是一种面向ENN的新兴治疗选择，无需切除癫痫发作区或癫痫病灶，旨在通过以自我反应的方式调节或破坏网络的关键节点（癫痫中枢）来控制癫痫发作或其他癫痫表现。2013年，NeuroPace-RNS系统获得美国食品药品监督管理局批准，用于患有医学难治性局灶性癫痫发作的成年患者。然而，NeuroPace系统主要在美国和欧洲国家使用，目前在中国尚不可用。在这里，我们采用了完全由中国团队开发的新型RNS系统，并进行了首次人体（FIM）研究。本研究的目的是证明对于DRE患者来说，这是一种安全有效的RNS系统。本研究在中国临床试验注册中心注册（www.chictr.org.cn；ChiCTR2200055247），并在每个参与中心获得机构审查委员会的批准，并获得书面知情同意。

致编辑：用于移植的已故供体(DD)肾脏的短缺仍然是一个持续关注的问题。尽管急性肾损伤（AKI）病变具有潜在的可逆性，但来自患有AKI的儿科供体的肾脏通常未得到充分利用，尤其是在儿科移植的背景下。通过实施从儿科供体到儿科受体（PTP）的单肾移植（SKT），我们可以优化可用肾脏的利用，增加儿科受体的数量。

致编辑：中国终末期肾病（ESKD）的首要病因是慢性肾小球肾炎（GN），占ESKD患者的45%。^[1]中国目前尚无全国性的关于慢性GN患者肾移植远期预后的大型研究。然而，在过去十年中，很少有针对欧洲人群的里程碑式研究^[2,3]和美国^[4]为本期提供了重要的参考数据。因此，我们建议开展一项全国性的多中心回顾性研究，由南京大学医学院金陵医院国家肾脏疾病临床医学研究中心于2017-2020年发起，回顾性分析和收集中国不同慢性GN患者肾移植术后的临床预后特征，为描述疾病结局、探讨相关危险因素、指导临床决策、改善中国肾移植患者的长期预后奠定基础。本研究项目经南京大学医学院金陵医院机构研究伦理委员会审查批准（编号：2017NZKYKS-002-01），按照赫尔辛基宣言获得所有参与者的书面知情同意书。