Volume 138 · Issue 08 · 2025

Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), leading to a high incidence of surgical interventions and significant disability. Despite its clinical relevance, no targeted pharmacological therapies are currently available. This review aims to explore the underlying mechanisms driving intestinal fibrosis and address unresolved scientific questions, offering insights into potential future therapeutic strategies. We conducted a literature review using data from PubMed up to October 2024, focusing on studies related to IBD and fibrosis. Intestinal fibrosis results from a complex network involving stromal cells, immune cells, epithelial cells, and the gut microbiota. Chronic inflammation, driven by factors such as dysbiosis, epithelial injury, and immune activation, leads to the production of cytokines like interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β. These mediators activate various stromal cell populations, including fibroblasts, pericytes, and smooth muscle cells. The activated stromal cells secrete excessive extracellular matrix components, thereby promoting fibrosis. Additionally, stromal cells influence the immune microenvironment through cytokine production. Future research would focus on elucidating the temporal and spatial relationships between immune cell-driven inflammation and stromal cell-mediated fibrosis. Additionally, investigations are needed to clarify the differentiation origins of excessive extracellular matrix-producing cells, particularly fibroblast activation protein (FAP)⁺ fibroblasts, in the context of intestinal fibrosis. In conclusion, aberrant stromal cell activation, triggered by upstream immune signals, is a key mechanism underlying intestinal fibrosis. Further investigations into immune–stromal cell interactions and stromal cell activation are essential for the development of therapeutic strategies to prevent, alleviate, and potentially reverse fibrosis.

Organ transplantation, particularly pediatric liver transplantation (LT), has transformed medical practice over the past six decades, providing life-saving interventions for children with end-stage liver disease. This review demonstrated the historical milestones of pediatric organ transplantation, emphasizing Japan’s contributions, mainly through the National Center for Child Health and Development. While early transplantation efforts in the 1950s and 1960s faced significant challenges, breakthroughs in preservation methods, immunosuppressive therapies, surgical techniques, and innovations such as living donor LT in Asia have greatly improved success rates. Japan’s pediatric LT landscape is distinct, primarily due to its reliance on living donor LT, shaped by cultural and religious influences that have traditionally restricted deceased donor organ donation. This review manuscript discusses Japan’s pioneering role in expanding the indications for pediatric LT to include rare conditions such as inherited metabolic disorders and hepatoblastoma. It highlights recent innovations such as hyper-reduced lateral segment grafts, machine perfusion, and minimally invasive surgery that have further improved outcomes. International collaboration has facilitated the sharing of expertise, advancing pediatric liver transplantation practice worldwide. Despite these achievements, challenges remain, particularly in light of Japan’s declining birth rate, which threatens the sustainability of pediatric transplant services. This review emphasizes the need for centralized transplant facilities, greater awareness of brain-dead organ donation, and continued medical advances to ensure that pediatric LT remains a viable, life-saving option for future generations.

Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell–cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.

Acute kidney injury (AKI) is a common clinically critical syndrome in hospitalized patients with high morbidity and mortality. At present, the mechanism of AKI has not been fully elucidated, and no therapeutic drugs exist. As known, glycolytic product lactate is a key metabolite in physiological and pathological processes. The kidney is an important gluconeogenic organ, where lactate is the primary substrate of renal gluconeogenesis in physiological conditions. During AKI, altered glycolysis and gluconeogenesis in kidneys significantly disturb the lactate metabolic balance, which exert impacts on the severity and prognosis of AKI. Additionally, lactate-derived posttranslational modification, namely lactylation, is novel to AKI as it could regulate gene transcription of metabolic enzymes involved in glycolysis or Warburg effect. Protein lactylation widely exists in human tissues and may severely affect non-histone functions. Moreover, the strategies of intervening lactate metabolic pathways are expected to bring a new dawn for the treatment of AKI. This review focused on renal lactate metabolism, especially in proximal renal tubules after AKI, and updated recent advances of lactylation modification, which may help to explore potential therapeutic targets against AKI.

Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated.

PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI).

We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (–8.05 mL/m², 95% CI: –14.88 to –1.23 mL/m²) and ACEI + BB + SGLT-2i (–18.94 mL/m², 95% CI: –36.97 to –0.61 mL/m²) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (–3254.21 pg/mL, 95% CI: –6242.19 to –560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP.

Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF.

PROSPERO; No. CRD42022354792.

器官是人体内的基本解剖实体，每个器官执行不同的生理功能并充当各种病理状况的部位。目前的医学研究和治疗主要集中在作为一个整体的个体或细胞和遗传水平上。然而，由于缺乏成熟的体外器官培养技术和模型，器官介观水平的研究明显落后于微观和宏观研究。这种滞后限制了研究成果的有效转化，并限制了区域研究和患病器官精确治疗的潜力。尽管鼠模型和细胞系有助于理解器官生物学和相关疾病，但它们未能复制人类器官复杂性和代谢功能的关键方面。值得注意的是，临床试验的失败通常归因于不准确的建模，特别是在动物模型中。

Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China.

Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan–Meier survival analysis was used to compare the cumulative incidence rate.

Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P <0.05).

This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics.

ClinicalTrials.gov, NCT03484806.

The correlation between the morphological structure of the patellofemoral joint (PFJ) and the severity of knee joint osteoarthritis (KOA) remains uncertain. This study aims to investigate the correlation between the severity of knee joint osteoarthritis and the alignment of patellofemoral and patellar height on radiographs.

This multi-center, retrospective study analyzed the magnetic resonance imaging (MRI) scans and anteroposterior radiographs of 534 adult outpatients with KOA. To evaluate the radiographic severity of KOA, anteroposterior radiographs of the knee and the Kellgren-Lawrence (K-L) grade were used. Knee MRI scans were used to measure the patellar length ratio (PLR), sulcus angle (SA), lateral patellar tilt angle (LPTA), and the distance between tibial tuberosity and trochlear groove (TT-TG). We examined the association between the configuration of the PFJ, arrangement, and harshness of the KOA. Information on participants’ demographics, such as age, sex, side, height, and weight, was collected. A chi-squared test was used for the correlation of radiographic severity of KOA with sex and the affected side. Spearman correlation was used for patellofemoral alignment or morphology and the radiographic severity of lateral KOA. Multiple linear regression models were used for the association between LPTA, SA, TT-TG, and severity of KOA after accounting for demographic variables.

The study comprised of 534 patients; of these, 339 (63%) were female. A total of 586 knees were evaluated in this study. Age showed a strong positive correlation with KOA severity (r = 0.516, P <0.01), whereas LPTA showed a strong negative correlation (r = –0.662, P <0.01). Additionally, SA (r = 0.616, P <0.05), and TT-TG showed a strong positive correlation (r = 0.770, P <0.01) with tibiofemoral osteoarthritis (TFOA) severity. Multiple linear regression analysis indicated that knee osteoarthritis severity (β = –2.946, P <0.001) and side (β = –0.839, P = 0.001) was associated with LPTA; knee osteoarthritis severity (β = 5.032, P <0.001) and age (β = –0.095, P <0.001) was associated with SA; knee osteoarthritis severity (β = 2.445, P <0.001), sex (β = –0.326, P = 0.041), body mass index (β = –0.061, P = 0.017) and age (β = –0.025, P <0.001) was associated with TT-TG.

Radiographic severity of KOA was positively associated with age, SA, and TT-TG but negatively associated with LPTA.

Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited.

This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed.

Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]–3rd quartile [Q3]: 11–44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset (P = 0.021) and transitioning to plaque psoriasis (P = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1–Q3: 2–41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1–Q3: 13.0–23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP.

The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.

Most studies have evaluated disability-adjusted life years (DALYs) of colorectal cancer (CRC) patients based on a set of generic disability weights (DWs). This study aimed to apply local CRC-stage-specific DWs to estimate the burden of DALYs for CRC (CRC-DALYs) in populations in China and consider the influence of local screening coverage of CRC.

A prevalence-based model was constructed using data from various sources. Years lived with disability (YLDs) were estimated mainly via cumulative prevalence data (based on CRC incidence rates, population numbers, and survival rates), stage-specific proportions of CRC, and DWs of the local population. Years of life lost (YLLs) were calculated based on the CRC mortality rates and standard life expectancies. CRC incidence and mortality rates for the years 2020, 2025, and 2030 were estimated by joinpoint regression, and the corresponding DALYs were predicted. The main assumption was made for CRC screening coverage. Sensitivity analyses were used to assess the impact of population, DWs, and coverage.

In 2017, among the Chinese population, the estimated number of CRC-DALYs was 4,303,314 (11.9% for YLDs). If CRC screening coverage rate in China (2.3%) remains unchanged, the overall DALYs in 2030 are predicted to increase by 37.2% (45.1% of those aged ≥65 years). More optimistically, the DALYs would then decrease by 0.7% in 2030 (from 5,902,454 to 5,860,200) if the coverage could be increased to 25.0%. A sensitivity analysis revealed that using local DWs would change the base-case values by 5.7%.

The estimated CRC-DALYs in China using population-specific DWs were considerably lower (with a higher percentage of YLDs) than the global burden of disease (GBD) estimates (5,865,004, of 4.6% for YLDs), suggesting the impact extent of applying local parameters. Sustainable scale-up CRC screening needs to be in place to moderate the growth trend of CRC-DALYs in China.

Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot.

Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness.

In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 µm vs. 412.00 ± 181.60 µm).

S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.

肝移植（LT）仍然是不可逆肝衰竭的主要治疗方法。然而，器官保存方面的挑战，特别是缺血再灌注损伤和供体肝脏脆弱性，导致移植后结果不佳。^[1,2]活性氧(ROS)的积累加剧了这些问题，导致炎症、组织损伤和移植物功能受损。^[3]二氧化铈纳米颗粒因其抗氧化、抗菌和抗纤维化特性而受到关注，并表现出多种酶活性，包括超氧化物歧化酶和过氧化氢酶的活性。^[4]我们开发了一种使用葡聚糖包被的二氧化铈纳米颗粒保存器官的创新系统₂NPs）纳入威斯康星大学（UW）解决方案，旨在通过减少氧化应激和炎症以及调节巨噬细胞极化来增强肝脏保存。

致编辑：慢性血栓栓塞性肺动脉高压（CTEPH）是一种罕见但严重的疾病，其特征是由于血栓栓塞事件和随后的血管重塑导致肺动脉阻塞，从而导致肺动脉高压（PH）。欧洲心脏病学会和欧洲呼吸学会在2022年PH指南中被归类为第4组，CTEPH会带来重大风险，包括进行性PH、右心室功能障碍和如果不治疗会导致死亡。尽管有既定的诊断和治疗指南，但由于缺乏有组织的登记，CTEPH的确切全国患病率在很大程度上仍然未知，估计为每百万人3至30例。尽管CTEPH通常被认为是继急性肺栓塞（PE）之后，但流行病学数据揭示了差异；研究表明，仅0.1%至3.8%的PE患者可能发生CTEPH。^[1,2]最近的报告表明，65.6%的CTEPH患者有急性PE病史，尽管这一比例因地区而异。^[3]治疗方案包括肺动脉内膜切除术（PEA）、riociguat和球囊肺血管成形术（BPA）。CTEPH显著影响患者的生活质量，导致呼吸急促和疲劳等症状，从而导致医疗利用和经济负担增加。在中国，有限的认识和延迟的诊断使CTEPH的管理进一步复杂化，强调了解决该疾病负担和提高医疗保健提供者认可度的研究的必要性。因此，本系统综述旨在利用PE患者的数据估计CTEPH的患病率，并调查中国人群中CTEPH的特征和管理模式。

致编辑：2型炎症是儿童中重度哮喘的主要驱动因素，可能导致下游嗜酸性粒细胞活化、免疫球蛋白E（IgE）产生、呼出一氧化氮分数（FeNO）增加和气道粘液产生。^[1]尽管中高剂量吸入性皮质类固醇联合长效β 2-受体激动剂（ICS-LABA）对儿童中重度哮喘进行了充分治疗，但症状持续存在或频繁恶化。^[2]研究表明，大约70-89%的中重度哮喘儿童有2型炎症，一种主要的内型是2型哮喘，其特征是存在升高的2型生物标志物，包括血或痰嗜酸性粒细胞、伴有过敏致敏的总IgE和FeNO。^[3]

致编辑：间隔子宫是最常见的先天性子宫畸形，与流产、早产和胎儿畸形的风险增加以及临床妊娠率降低有关。欧洲分类将隔膜子宫定义为具有超过子宫壁厚度50%的内部宫底压痕和小于子宫壁厚度50%的外部压痕。^[1]

致编辑：常见的呼吸道疾病如慢性阻塞性肺病（COPD）和哮喘在世界范围内引起显著的健康负担。^[1,2]气道/肺部微生物组和微生物代谢物已被证明与多种呼吸道疾病密切相关。^[3]然而，很少有相关研究显示呼吸道疾病优势菌代谢产物的特征和横向比较。此外，大多数结果基于微生物组序列（尤其是肠道微生物组的序列）和非靶向代谢组学的关联分析，没有证据表明代谢物是由某些细菌直接产生和分泌的。^[4]在此背景下，我们的研究旨在分析和比较呼吸道疾病病常见细菌的关键代谢物和代谢途径。

致编辑：肥胖是一个突出的全球健康问题，对心脏代谢疾病（CMDs，包括心血管疾病[CVDs]和糖尿病）造成相当大的负担。除了对单一CMD的关注之外，人们越来越重视它们的共病，称为心脏代谢多病（CMM）。CMM患病率的上升给个人和医疗保健系统带来了巨大的风险。值得注意的是，1999年至2018年间，美国CMM的患病率从9%增加到14%，而在中国，2010年至2016年间，CMM的患病率几乎增加了两倍，从2%增加到6%。^[1,2]

致编辑：特应性皮炎(AD)是一种慢性炎症性皮肤病，以复发性湿疹性病变和剧烈瘙痒为特征，影响全球约15-20%的儿童和高达10%的成人。^[1]AD的存在显著损害患者的生活质量，并给社会带来巨大的经济负担。近年来，AD和淋巴瘤之间的潜在联系引起了研究人员和临床医生的极大关注。淋巴瘤是淋巴系统的恶性肿瘤，由于其高死亡率潜力而造成重大健康风险。^[2]然而，调查AD和淋巴瘤之间潜在相关性的观察性研究产生了不一致的结果。因此，AD和淋巴瘤之间的联系仍有争议，值得进一步研究。

致编辑：生物制剂已成功用于治疗银屑病；然而，一些患者出现反常反应，特别是银屑病样和湿疹样反应。湿疹样反常反应(EPR)发生在1%-6%的肿瘤坏死因子(TNF)-α抑制剂、2.4%的白细胞介素(IL)-12/23抑制剂、3.5%的IL-17抑制剂和0.01%的IL-23抑制剂治疗的病例中。^[1]在实践中，IL-17A抑制剂诱导的EPRs的发生率差异很大^[2,3,4]在一些严重的情况下，生物制剂可能不得不停用。^[5]

包括十二指肠和空肠的近端小肠被广泛认为是人类营养消化和吸收的主要部位。^[1]值得注意的是，其管腔环境表现出不同的组织学和生理学特征，包括纵向pH梯度、氧压变化和不同浓度的抗菌肽。^[2]此外，小肠是由重复的隐窝-绒毛单位组成的高度组织化的结构。在小鼠中，已鉴定上皮细胞、免疫细胞和间充质细胞在沿隐窝-绒毛轴的基因表达模式中表现出显著的空间变异性。然而，人类小肠的空间表达异质性在很大程度上仍未被探索。