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Background: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma, but prognosis is still unsatisfactory. Recently, hepatic arterial infusion chemotherapy (HAIC), and immune checkpoint inhibitors showed promising results for advanced hepatocellular carcinoma. Considering different anti-malignancy mechanisms, combining these three treatments may improve outcomes. This study aimed to compare the efficacy and safety of lenvatinib, toripalimab, plus HAIC versus lenvatinib for advanced hepatocellular carcinoma. Methods: This was a retrospective study including patients treated with lenvatinib [8 mg (⩽60 kg) or 12 mg (>60 kg) once daily] or lenvatinib, toripalimab plus HAIC [LeToHAIC group, lenvatinib 0–1 week prior to initial HAIC, 240 mg toripalimab 0–1 day prior to every HAIC cycle, and HAIC with FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 h, every 3 weeks)]. Progression-free survival, overall survival, objective response rate, and treatment-related adverse events were compared. Results: From February 2019 to August 2019, 157 patients were included in this study: 71 in the LeToHAIC group and 86 in the lenvatinib group. The LeToHAIC group showed longer progression-free survival (11.1 versus 5.1 months, p < 0.001), longer overall survival (not reached versus 11 months, p < 0.001), and a higher objective response rate (RECIST: 59.2% versus 9.3%, p < 0.001; modified RECIST: 67.6% versus 16.3%, p < 0.001) than the lenvatinib group. In addition, 14.1% and 21.1% of patients in the LeToHAIC group achieved complete response of all lesions and complete response of the intrahepatic target lesions per modified RECIST criteria, respectively. Grade 3/4 treatment-related adverse events that were more frequent in the LeToHAIC group than in the lenvatinib group included neutropenia (8.5% versus 1.2%), thrombocytopenia (5.6% versus 0), and nausea (5.6% versus 0). Conclusions: Lenvatinib, toripalimab, plus HAIC had acceptable toxic effects and might improve survival compared with lenvatinib alone in advanced hepatocellular carcinoma.

With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, an important group of complementary and alternative medicine (CAM) therapy. With a long history of herbal usage for the clinical management of a variety of diseases in indigenous cultures, the success rate of developing a new drug from herbal medicinal preparations should, in theory, be higher than that from chemical synthesis. While the endeavor for drug discovery from herbal medicines is “experience driven,” the search for a therapeutically useful synthetic drug, like “looking for a needle in a haystack,” is a daunting task. In this paper, we first illustrated various approaches of drug discovery from herbal medicines. Typical examples of successful drug discovery from botanical sources were given. In addition, problems in drug discovery from herbal medicines were described and possible solutions were proposed. The prospect of drug discovery from herbal medicines in the postgenomic era was made with the provision of future directions in this area of drug development.

This two-sample Mendelian randomization (MR) study was conducted to investigate the causal associations between type 2 diabetes mellitus (T2DM) and the risk of pancreatic cancer (PaCa), as this causal relationship remains inconclusive in existing MR studies. The selection of instrumental variables for T2DM was based on two genome-wide association study (GWAS) meta-analyses from European cohorts. Summary-level data for PaCa were extracted from the FinnGen and UK Biobank databases. Inverse variance weighted (IVW) and four other robust methods were employed in our MR analysis. Various sensitivity analyses and multivariable MR approaches were also performed to enhance the robustness of our findings. In the IVW and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analyses, the odds ratios (ORs) for each 1-unit increase in genetically predicted log odds of T2DM were approximately 1.13 for PaCa. The sensitivity tests and multivariable MR supported the causal link between T2DM and PaCa without pleiotropic effects. Therefore, our analyses suggest a causal relationship between T2DM and PaCa, shedding light on the potential pathophysiological mechanisms of T2DM’s impact on PaCa. This finding underscores the importance of T2DM prevention as a strategy to reduce the risk of PaCa.

Background Patients with a 5‐year recurrence‐free survival post liver resection for colorectal cancer liver metastases (CRLM) are considered to be potentially cured. However, there is a deficit of data on long‐term follow‐up and the recurrence status among these patients in the Chinese population. We analyzed real‐world follow‐up data of patients with CRLM who underwent hepatectomy, explored the recurrence patterns, and established a prediction model for a potential cure scenario. Methods Patients who underwent radical hepatic resection for CRLM during 2000–2016, with actual follow‐up data for at least 5 years, were enrolled. The observed survival rate was calculated and compared among the groups with different recurrence patterns. The predictive factors for 5‐year non‐recurrence were determined using logistic regression analysis; a recurrence‐free survival model was developed to predict long‐term survival. Results A total of 433 patients were included, of whom 113 patients were found non‐recurrence after 5 years follow‐up, with a potential cure rate of 26.1%. Patients with late recurrence (>5 months) and lung relapse showed significantly superior survival. Repeated localized treatment significantly improved the long‐term survival of patients with intrahepatic or extrahepatic recurrences. Multivariate analysis showed that RAS wild‐type CRC, preoperative CEA <10 ng/ml, and liver metastases ≤3 were independent factors for a 5‐year disease‐free recurrence. A cure model was developed based on the above factors, achieving good performance in predicting long‐term survival. Conclusions About one quarter patients with CRLM could achieve potential cure with non‐recurrence at 5‐year after surgery. The recurrence‐free cure model could well distinguish the long‐term survival, which would aid clinicians in determining the treatment strategy. With the advances in treatment for colorectal liver metastases (CRLM), accurately predicting recurrence‐free survival post hepatectomy has become increasingly important. This study retrospectively analyzed patients with CRLM who underwent surgery with actual follow‐up over 5 years; we found that approximately one quarter of patients got a potential cure chance without recurrence. Patients with RAS wild‐type, preoperative CEA <10 ng/mL, and liver metastases ≤3 were shown to have a higher chance of cure rate after hepatic resection for CRLM.

In the urbanization process, phenomena such as the urban heat island effect exacerbate climatic deteriorations, leading to environmental issues in cities. Campus areas, as significant ecological components within the urban environment, play a crucial role in environmental regulation. This paper investigates the impact of outdoor physical environments in campuses on users’ thermal comfort from the perspective of thermal comfort. Using surveys, meteorological measurements, and behavioral analysis, this study examines four distinctive spaces within a campus in Xi’an, establishing a thermal comfort baseline for the population in Xi’an’s campus spaces. The research results indicate: (1) Globe temperature (T g ), air velocity (V a ), air temperature (T a ), and ground temperature (G) are the primary factors affecting students’ thermal sensations in campus open spaces. Respondents tended to improve their thermal sensations through changes in humidity and solar radiation. (2) In the campus open spaces of Xi’an, the overall NPET of the subjects was 13.9 °C, with the NPETR ranging from 9.4 to 18.4 °C. (3) The preferred warmth temperature for university students in Xi’an is 15.15 °C, which is 1.25 °C higher than the NPET (13.9 °C).

In recent years, increasing numbers of people have been choosing herbal medicines or products to improve their health conditions, either alone or in combination with others. Herbs are staging a comeback and herbal “renaissance” occurs all over the world. According to the World Health Organization, 75% of the world’s populations are using herbs for basic healthcare needs. Since the dawn of mankind, in fact, the use of herbs/plants has offered an effective medicine for the treatment of illnesses. Moreover, many conventional/pharmaceutical drugs are derived directly from both nature and traditional remedies distributed around the world. Up to now, the practice of herbal medicine entails the use of more than 53,000 species, and a number of these are facing the threat of extinction due to overexploitation. This paper aims to provide a review of the history and status quo of Chinese, Indian, and Arabic herbal medicines in terms of their significant contribution to the health promotion in present-day over-populated and aging societies. Attention will be focused on the depletion of plant resources on earth in meeting the increasing demand for herbs.

The concept of initiators for continuous activator regeneration (ICAR) in atom transfer radical polymerization (ATRP) is introduced, whereby a constant source of organic free radicals works to regenerate the$Cu^{I}$activator, which is otherwise consumed in termination reactions when used at very low concentrations. With this technique, controlled synthesis of polystyrene and poly(methyl methacrylate) ($M_{w}/M_{n} \\textless 1.2$) can be implemented with catalyst concentrations between 10 and 50 ppm, where its removal or recycling would be unwarranted for many applications. Additionally, various organic reducing agents (derivatives of hydrazine and phenol) are used to continuously regenerate the$Cu^{I}$activator in activators regenerated by electron transfer (ARGET) ATRP. Controlled polymer synthesis of acrylates ($M_{w}/M_{n}$< 1.2) is realized with catalyst concentrations as low as 50 ppm. The rational selection of suitable Cu complexing ligands {tris[2-(dimethylamino)ethyl]amine (Me₆TREN) and tris[(2-pyridyl)methyl]amine (TPMA)) is discussed in regards to specific side reactions in each technique (i.e., complex dissociation, acid evolution, and reducing agent complexation). Additionally, mechanistic studies and kinetic modeling are used to optimize each system. The performance of the selected catalysts/reducing agents in homo and block (co)polymerizations is evaluated.

Objective This study aims to conduct a systematic review to summarize the rare retinal toxicity associated with intravitreal ganciclovir injections. Methods A retrospective analysis was performed on patients who received intravitreal ganciclovir injections at our institution (Jan 2021–Dec 2024). Following the PRISMA guidelines, databases such as PubMed, Cochrane Library, and Scopus were systematically searched to identify reported cases of retinal toxicity in the literature. Results A total of 16 cases (17 eyes) were included, comprising 5 cases (5 eyes) from our institution and 11 cases (12 eyes) from 11 published articles. The average age was 52 years (range, 26–79), with 13 patients (81.3%) being male. Thirteen cases were diagnosed with cytomegalovirus (CMV) retinitis, and 3 with acute retinal necrosis (ARN). Based on multimodal imaging, retinal toxicity was classified into three categories: crystalline retinopathy (6 eyes, 35.3%), toxic pigmentary retinopathy (7 eyes, 41.2%), and macular toxicity (8 eyes, 47.1%). Notably, crystalline retinopathy and toxic pigmentary retinopathy often coexisted with macular toxicity. All cases received ≥ 2 mg intravitreal ganciclovir, except one silicone oil-filled eye that received 1 mg. Approximately two-thirds of injections exceeded 4 mg per administration. Conclusion This study provides an in-depth examination of the clinical features of retinal toxicity induced by intravitreal ganciclovir, systematically detailing its multimodal imaging characteristics and key points for early detection. The findings highlight that while intravitreal ganciclovir is effective in controlling primary disease progression, its potential for retinal toxicity requires careful consideration.

Near-isothermal electrically assisted tensile tests were performed on Ti–6Al–4V alloy sheet by programmed current–time loading curve and real-time monitoring via infrared thermal imaging. Comparing the results of thermal-assisted tension (TAT) and electrically assisted tension (EAT) at equivalent tensile temperatures, it is found that the flow stress and elongation under EAT are generally lower than the ones under TAT. Moreover, significant flow softening of 14–88 MPa which increases with current density and strain is found in EAT, indicating the existence of electroplasticity. From microstructure observations, dislocation annihilation, formation of dislocation walls, sub-grains, and dynamic recrystallization were found under the EAT process at a temperature lower than the conventional recrystallization temperature range. In addition, electric pulse is provided to accelerate the α→β phase transformation by promoting local diffusion, resulting in the increased volume fraction of β phase from 23.02 to 31.42% and the formation of many acicular α phase during the rapid cooling process after EAT at 20 A/mm 2 . The enhanced flow softening in EAT is explained as the comprehensive influences of electrically induced α→β phase transformation, dynamic recovery, dynamic recrystallization, and related enhanced local Joule heating at newly born grain boundaries. Graphical abstract

The infiltration of tumor-associated macrophages (TAMs) is associated with tumor progression and poor prognosis in endometrial cancer (EC). Collagen triple helix repeat containing 1 (CTHRC1), a secreted ECM protein, has been reported to have important roles in promoting cancer invasion and metastasis, but the functional role of CTHRC1 and its association with TAMs in EC remain unclear. Here we report that, in EC patients, CTHRC1 expression was up-regulated in endometrial cancer tissues compared with normal endometrium (P < 0.0001), and is positively correlated with tumor grade and depth of myometrial invasion (P = 0.024 and P = 0.0002, respectively). Meanwhile, CTHRC1 expression was positively correlated with an increased number of infiltrating TAMs, especially M2-like TAMs (P = 0.003, P = 0.001). In the tumor microenvironment of EC, CTHRC1 not only promoted myometrial invasion by interacting with Integrin β3-Akt signaling pathway, but also promoted infiltration of M2-like TAMs by upregulating Fractalkine chemokine receptor (CX3CR1) expression in macrophages. Changing levels of recombinant CTHRC1 protein (rCTHRC1) promoted tumor migration and invasion via enhancing macrophage recruitment in vitro. In summary, our findings eventually provided a novel role for CTHRC1 in remodeling the tumor immune microenvironment to promote tumor metastasis in EC patients.