For HCQ retinopathy with CME, acupuncture combined with periocular injection can be used to improve the CME and protect the central vision. Subsequent research endeavors involving a more extensive cohort and extended observation periods are warranted to evaluate the effectiveness and safety profile of the intervention.
Humans ; Macular Edema/drug therapy* ; Acupuncture Therapy/methods* ; Hydroxychloroquine/therapeutic use* ; Female ; Retinal Diseases/chemically induced* ; Middle Aged ; Combined Modality Therapy ; Male

OBJECTIVE: To evaluate the therapeutic effect of Yu Melody relaxation training (YMRT) combined with Jianpi Jieyu Decoction (JJD) in treating patients with insomnia disorders (ID). METHODS: In this randomized controlled study, 94 ID patients were included from Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2022 to January 2024. They were randomly assigned to the YMRT group (47 cases, YMRT plus JJD) and the control group (47 cases, oral JJD) using a random number table. Both treatment administrations lasted for 4 weeks, with a 2-week follow-up. The primary outcome was change in Insomnia Severity Index (ISI) scores from baseline to 4 weeks of intervention. Secondary outcomes included ISI response at week 4, as well as ISI, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder 7-item (GAD-7) scores at baseline and weeks 1, 2, 3, 4, and 6. Additionally, Pittsburgh Sleep Quality Index (PSQI) scores were evaluated at baseline and weeks 4 and 6. Adverse events (AEs) were recorded and compared between groups. RESULTS: Five patients in each group did not complete the protocol requirements. The overall dropout rate was 10.64%. The full analysis set included all 47 cases in each group. The ISI score decreased significantly at week 4 from baseline in the YMRT group compared with the control group, with a between-group difference of -3.2 points [95% confidence interval (CI): -5.08 to -1.34; P<0.05]. The ISI response at week 4 in the YMRT group was significantly higher than that in the control group (85.11% vs. 51.06%), with a between-group difference of 34.05% (95% CI: 13.77% to 50.97%; P<0.05). At week 6, the YMRT group demonstrated greater reductions from baseline than the control group, with between-group differences of -2.1 points (-95% CI: -3.49 to -0.64; P<0.05) for PHQ-9 scores, -3.5 points (95% CI: -5.21 to -1.85; P<0.05) for PSQI scores, and -1.9 points (95% CI: -3.47 to -0.28; P<0.05) for GAD-7 scores. Moreover, at weeks 4 and 6, the ISI and PSQI scores in the YMRT group were significantly lower than those in the control group (P<0.05); and at week 6, the PHQ-9 score in the YMRT group was significantly lower (P<0.05). There was no significant difference in the incidence rates of AEs between the two groups (8.51% vs. 4.26%, P>0.05). CONCLUSIONS YMRT combined with oral JJD could improve sleep quality and alleviate depressive and anxiety symptoms in patients with ID. This combined therapy was effective and safe, and its effect was superior to oral JJD alone. (Registration No. ChiCTR2200063884).
Humans ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Relaxation Therapy/methods* ; Middle Aged ; Adult ; Treatment Outcome ; Combined Modality Therapy

OBJECTIVES: Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and remains incurable. Patients with primary refractory multiple myeloma (PRMM) show poor response to initial induction therapy. This study aims to develop a machine learning-based model to predict treatment response in newly diagnosed multiple myeloma (NDMM) patients, in order to optimize therapeutic strategies. METHODS: NDMM and post-treatment MM patients hospitalized in the Department of Hematology, Third Xiangya Hospital, Central South University, between August 2022 and July 2023 were enrolled. Post-treatment MM patients were categorized into PRMM patients and treatment-responsive MM (TRMM) patients based on therapeutic efficacy. Serum metabolites were detected and analyzed via metabolomics. Based on the metabolomics analysis results and combined with transcriptomic sequencing data of NDMM patients from databases, differentially expressed amino acid metabolism-related genes (AAMGs) among post-treatment NDMM patients with varying therapeutic outcomes were screened. Using bioinformatics analyses and machine learning algorithms, a predictive model for treatment response in NDMM was constructed and used to identify patients at risk for PRMM. RESULTS: A total of 61 patients were included: 22 NDMM, 23 TRMM, and 16 PRMM patients. Significant differences in metabolite levels were observed among the 3 groups, with differential metabolites mainly enriched in amino acid metabolism pathways. Follow-up data were available for 16 of the 22 NDMM patients, including 12 treatment responders (ND_TR group) and 4 with PRMM (ND_PR group). A total of 23 differential metabolites were identified between these 2 groups: 6 metabolites (e.g., tryptophan) were upregulated and 17 (e.g., citric acid) were downregulated in the ND_TR group. Transcriptomic data from 108 TRMM and 77 PRMM patients were analyzed to identify differentially expressed AAMGs, which were then used to construct a prediction model. The area under the receiver operating characteristic curve (AUC) for the model exceeded 0.8, and AUC values in 3 external validation cohorts were all above 0.7. CONCLUSIONS This study delineated the metabolic alterations in MM patients with different treatment response, suggesting that dysregulated amino acid metabolism may be associated with poor treatment response in PRMM. By integrating metabolomics and transcriptomics, a machine learning-based predictive model was successfully established to forecast treatment response in NDMM patients.
Humans ; Multiple Myeloma/drug therapy* ; Machine Learning ; Male ; Female ; Metabolomics/methods* ; Middle Aged ; Aged ; Treatment Outcome ; Transcriptome ; Computational Biology ; Adult ; Multiomics

OBJECTIVES: Managing patients with refractory head and neck cancer pain is one of the more challenging issues in clinical practice, and traditional intrathecal drug delivery also fails to provide adequate analgesia. There are currently no comprehensive and effective treatment methods. This study aims to observe the efficacy and safety of treating intractable head and neck cancer pain with morphine pump via lumbar approach to the prepontine cistern. METHODS: A total of 18 patients with intractable head and neck cancer pain treated with prepontine cistern morphine pumps were selected from the Department of Pain Management, Second Xiangya Hospital, Central South University between September 2019 and July 2023. Statistical analysis was performed on patients' preoperative and postoperative (1 week, 1 month, and 2 months after surgery), Numerical Rating Scale (NRS) scores, Self-Rating Depression Scale (SDS) scores, daily oral morphine consumption, the number of daily breakthrough pain episodes, and postoperative daily intrathecal morphine dosage. RESULTS: The NRS scores, SDS scores, daily oral morphine consumption, and the number of daily breakthrough pain episodes of patients at each time point after surgery were significantly lower than before surgery (all P<0.05). With the gradual increase in the dosage of intrathecal morphine, the daily oral morphine consumption of patients at each postoperative time point was significantly reduced compared to preoperative levels (all P<0.05). The complications related to the operation were mild, including nausea in 5 cases (31.3%), headache in 2 cases (12.5%); hypotension, urine retention, hypersomnia and constipation in 1 case (6.3% each), and no serious adverse events occurred. All improved and were discharged after symptomatic treatment. CONCLUSIONS The implantation of prepontine cistern morphine pump effectively controls intractable head and neck cancer pain, demonstrating characteristics of minimal invasiveness, mild side effects, and low medication dosage under the premise of standardized procedures.
Humans ; Morphine/administration & dosage* ; Male ; Female ; Middle Aged ; Head and Neck Neoplasms/surgery* ; Analgesics, Opioid/administration & dosage* ; Cancer Pain/drug therapy* ; Pain, Intractable/etiology* ; Aged ; Adult ; Infusion Pumps, Implantable ; Pain Management/methods*

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Breast cancer is one of the most common and fatal malignancies among women worldwide, and its treatment efficacy is often limited by drug resistance and the presence of undruggable targets. Traditional small-molecule drugs have difficulty effectively modulating certain critical targets such as transcription factors and non-coding RNAs, necessitating new therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) function by recruiting pathogenic proteins to the cellular ubiquitin-proteasome system, thereby inducing their specific degradation. In contrast, ribonuclease-targeting chimeras (RIBOTACs) utilize small-molecule ligands but bind to RNA and direct endogenous RNases to selectively degrade pathogenic RNA molecules. By employing a "degradation rather than inhibition" mechanism, targeting chimera technology broadens the druggable landscape and offers a novel precision therapeutic strategy for breast cancer, particularly for refractory and drug-resistant cases. This approach not only overcomes the limitations of traditional drugs, such as the absence of suitable binding sites or poor selectivity, but also reduces required dosages and potential adverse effects. Recent studies have preliminarily demonstrated the therapeutic potential of PROTACs and RIBOTACs in breast cancer, encompassing target design, mechanistic investigation, and preclinical as well as early clinical applications. Research into these technologies reveals their ability to tackle previously undruggable targets, thereby providing theoretical support for the development of safer and more effective precision therapies for breast cancer. In the future, with advances in drug delivery systems and clinical trials, PROTACs and RIBOTACs are expected to be used synergistically with immunotherapy and chemotherapy, offering breast cancer patients more promising comprehensive treatment options and potentially driving oncology toward broader intervention of undruggable targets.
Humans ; Breast Neoplasms/drug therapy* ; Female ; Proteolysis ; Ribonucleases/metabolism* ; Molecular Targeted Therapy/methods* ; Antineoplastic Agents/therapeutic use*

Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade (ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified; some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration (FDA) for clinical treatment. However, limited responses and immune-related adverse events (irAEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoplasms/drug therapy* ; Immunotherapy/methods* ; Animals

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as certain forms of non-melanoma skin cancer (NMSC) or keratinocyte carcinoma, are the most common forms of malignant neoplasms worldwide (Sharp et al., 2024). BCC and cSCC have been identified as two major components of NMSC, comprising one-third of all malignancies (Burton et al., 2016). Generally speaking, patients with NMSC tend to have relatively favorable survival outcomes, while different histopathological subtypes of NMSC exhibit distinct biological behaviors (Stătescu et al., 2023). Keratinocyte carcinoma, although not considered as deadly as melanoma, tends to metastasize if left untreated (Civantos et al., 2023; Nanz et al., 2024). cSCC can evolve locally, then aggressively metastasize, invade, and even lead to fatal consequences in a subset of patients (Winge et al., 2023). A solid, pigmented, smooth plaque or a hyperkeratotic papule with or without central ulceration and hemorrhage appears to be characteristic of cSCC (Thompson et al., 2016; Zhou et al., 2023). Of note, a rare type of intraepidermal cSCC in situ often appears as a velvety, demarcated, slightly raised erythematous plaque on the genitalia of men (Yamaguchi et al., 2016). Accounting for approximately 16.0% of scalp tumors and with a rising incidence, cSCC is now the second most common NMSC in humans (Verdaguer-Faja et al., 2024). According to the latest statistics, up to 2%‒5% of cSCCs in situ may gradually progress into invasive cSCCs in the final step (Rentroia-Pacheco et al., 2023). Several risk factors for the carcinogenesis and development of cSCC have been identified, including age, accumulative exposure to ultraviolet light radiation A and B, human papillomavirus infection, arsenic ingestion, chronic scarring, xeroderma pigmentosa, a relevant history of ionizing radiation, androgenetic alopecia in males, and immunosuppression therapy (Martinez and Otley, 2001; Welsch et al., 2012; Mortaja and Demehri, 2023).
Humans ; Aminolevulinic Acid/therapeutic use* ; Skin Neoplasms/pathology* ; Photochemotherapy/methods* ; Female ; Carcinoma, Squamous Cell/pathology* ; Middle Aged ; Photosensitizing Agents/therapeutic use* ; Carcinoma, Basal Cell/drug therapy*

BACKGROUND: Neoadjuvant therapy enhances the possibility of achieving radical resection and improves the prognosis for locally advanced gastric cancer (GC). However, there is a lack of evidence regarding the optimal extent of resection for locally advanced proximal GC after neoadjuvant therapy. METHODS: In this study, 330 patients underwent resection in Peking University Cancer Hospital, with curative intent after neoadjuvant therapy for histologically confirmed proximal GC from January 2009 to December 2022. RESULTS: In this study, 45 patients underwent proximal gastrectomy (PG), while 285 underwent total gastrectomy (TG). After propensity-score matching, 110 patients (71 TG and 39 PG) were included in the analysis. No significant differences between PG and TG regarding short-term outcomes and long-term prognosis were found. Specifically, PG demonstrated comparable overall survival to TG ( P = 0.47). Subgroup analysis revealed that although not statistically significant, PG showed a potential advantage over TG in overall survival for patients with tumor-long diameters less than 4 cm ( P  = 0.31). However, for those with a long diameter larger than 4 cm, TG had a better survival probability ( P  = 0.81). No substantial differences were observed in baseline characteristics, surgical safety, postoperative recovery, and postoperative complications. CONCLUSION For locally advanced proximal GC with objective response to neoadjuvant therapy (long diameter <4 cm), PG is an alternative surgical procedure.
Humans ; Stomach Neoplasms/drug therapy* ; Gastrectomy/methods* ; Neoadjuvant Therapy/methods* ; Male ; Female ; Middle Aged ; Propensity Score ; Aged ; Adult ; Retrospective Studies

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome