Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

Cancer is a serious global health problem and a major cause of human death. Conventional cancer treatments often run the risk of impairing vital organ functions. Anticancer peptides (ACPs) are considered to be one of the most promising therapeutic agents against common human cancers due to their small sizes, high specificity, and low toxicity. Since ACP recognition is highly limited to the laboratory, expensive, and time-consuming, we proposed pLM4ACP, a model for predicting ACPs based on machine learning and protein language models. In this model, the protein language model ProtT5 was used to extract the features of ACPs, and the extracted features were input into the support vector machine (SVM) classification algorithm for optimization and performance evaluation. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 0.763, F1-score of 0.767, Matthews correlation coefficient of 0.527, and area under the curve of 0.827 on the independent test set. This study constructs an efficient anticancer peptide prediction model based on protein language models, further advancing the application of artificial intelligence in the biomedical field and promoting the development of precision medicine and computational biology.
Machine Learning ; Antineoplastic Agents/chemistry* ; Humans ; Peptides/chemistry* ; Support Vector Machine ; Algorithms ; Computational Biology/methods* ; Neoplasms/drug therapy*

With the transformation of the concept and model of mental health service in China,the participation of social work in multidisciplinary team cooperation in mental health has become an important development trend.In order to explore the mode and path of multidisciplinary treatment involving social work in mental health,this study selected two typical wards of Shanghai Mental Health Center as typical cases through the double-case study method,and conducted in-depth interviews and participatory observation of the medical teams in the wards.The results show that medical social workers can participate in multi-disciplinary comprehensive treatment through the path of"service embedding-relationship embedding-system embedding".In this process,the"resource-demand"response mode,power acquisition,daily interaction,discourse integration,and service mecha-nism reconstruction are important action strategies to achieve the service embeddedness of social workers.Different strategies de-termine the final different service modes.In the future,the participation of medical social work in multidisciplinary comprehen-sive treatment mode should not only strengthen micro-practice,but also form macro-institutional guarantee.

[Objective] To explore the application of pelvic floor ultrasonography in the treatment of mixed urinary incontinence (MUI) by transvaginal retropubic midurethral synthetic sling (RMUS), in order to understand the relationship between the morphological changes of pelvic floor structures and the efficacy of RMUS. [Methods] Clinical data of 44 female MUI patients undergoing RMUS during Jan.2018 and Dec.2020 were retrospectively analyzed.Urodynamics detected detrusor overactivity (DO) in 9 cases (20.5%). During RMUS procedure, the tension of the sling was adjusted based on the anatomical landmarks. The changes of ultrasonic parameters before and after operation, the relationship between the ultrasonic results, surgical efficacy and urodynamic results were analyzed. [Results] The patients averaged (58.59±9.08) years, with the body mass index being 24.71±2.77.The subjective cure rate was 91.3% (21/23) 3 months after surgery, and 85.0% (34/40) 2 years after surgery.Pelvic floor ultrasonography showed significant differences in posterior urethravesical angel at rest and during Valsalva, bladder neck descent distance and the rate of urethral funneling during Valsalva (P<0.05). According to the group analysis of the preoperative ultrasonic results, there was no statistical significance in the subjective cure rate between the funneling group and the non-funneling group during Valsalva, and the bladder neck non downward group/mild downward group/moderate downward group/severe downward group during Valsalva 3 months and 2 years after surgery (P>0.05). At 3-month follow-up, all pre-RMUS urethral funneling during Valsalva disappeared in patients without preoperative DO.Comparatively, 50.0% (3/6) urethral funneling still presented in DO patients, who had a lower cure rate (55.6%, 5/9) at the 2-year follow-up. [Conclusion] RMUS can reduce the posterior urethravesical angel at rest and during Valsalva, reduce bladder neck descent distance and the rate of urethral funneling during Valsalva in MUI patients, which can enhance urinary continence.There seems to be a correlation between DO and urethral funneling during Valsalva, while RMUS may potentially reverse the two markers.

Objective To explore the efficacy of retropubic midurethral synthetic sling(RMUS)in relieving urgency and urge urinary incontinence(UUI)symptoms in patients with mixed urinary incontinence(MUI).Methods Clinical data of 44 female MUI patients treated with RMUS during Jan.2018 and Dec.2020 in Shanghai Renji Hospital were retrospectively analyzed.All patients had positive results in stress test and Marshall-Marchetti test before operation,and 27 of them completed ICIQ-FLUTS-LF questionnaire.Urodynamic(UDS)tests suggested that 9 patients(20.5％)presented detrusor overactivity(DO).During RMUS procedure,the tension of the sling was adjusted based on the anatomical landmarks.The postoperative efficacy and improvement of urinary incontinence were analyzed.Results The patients aged(58.59±9.08)years,with a body mass index of 24.71±2.77.Among the 40 patients who completed telephone interview 2 years after surgery,the subjective cure rate was 85.0％(34/40).Among the 27 patients with records of questionnaires before and after surgery,there were significant differences in the incidence of urine leakage[100％(27/27)vs.18.5％(5/27)],stress urinary incontinence(SUI)[100％(27/27)vs.18.5％(5/27)]and UUI[70.4％(19/27)vs.29.6％(8/27)](P＜0.05).However,no statistical differences were found regarding nocturia voiding episode(≥1 times),urgency,dysuria,hesitancy,strain to void,intermittent stream and enuresis(P＞0.05).Based on preoperative UDS test,there were significant differences regarding the subjective cure rate in patients with or without preoperative DO[55.6％(5/9)vs.93.5％(29/31)],incidence of SUI[66.7％(4/6)vs.4.8％(1/21)],and UUI[66.7％(4/6)vs.19.0％(4/21)](P＜0.05),while there was no statistical difference regarding urgency[66.7％(4/6)vs.33.3％(7/21)](P＞0.05).Conclusion RMUS is effective in treating MUI patients with positive stress test and Marshall-Marchetti test results,which can relieve SUI and UUI symptoms,but has no effects on urgency symptoms.DO on preoperative urodynamics results in poorer subjective outcomes.

Objective:To analyze the functional connectivity (FC) characteristics of sensory motor network (SMN) in patients with bipolar disorder type Ⅰ (BD-Ⅰ) by independent component analysis (ICA), and explore the correlation between abnormal SMN and clinical symptoms.Methods:Eighteen patients with BD-Ⅰ (BD-Ⅰ group) and 20 matched normal controls (HC group) were included.Both groups received resting state fMRI (rs-fMRI) scanning.Based on ICA-fMRI data, one-sample t-test and two-sample t-test were used to analyze the components of SMN and to explore abnormal brain regions between the two groups.Functional network analysis (FNC) was also used to explore the functional connectivity between SMN and other brain networks.Pearson correlation analysis were conducted by SPSS 17.0 to measure the potential associations between intra-and inter-network functional connectivity and age, education, score of Bech-Rafaelsen mania rating scale (BRMS), score of positive and negative syndrome scale (PANSS) and other indicators. Results:In BD-Ⅰ group, the functional connection in the right paracentral lobule (MIN: x=8, y=-32, z=68, t=4.86, P<0.001) and the right postcentral gyrus (MIN: x=41, y=-26, z=53, t=3.33, P<0.001) in SMN were higher than those in HC group.Compared with HC group, the connectivity value in patients with BD-Ⅰ increased between SMN-DAN (0.247±0.073, -0.078±0.080, t=-2.974, P<0.01, FDR adjusted), while the connectivity value decreased between SMN-DMN(-0.037±0.054, 0.272±0.067, t=3.520, P<0.01, FDR adjusted) and between SMN-rFPN(-0.034±0.055, 0.231±0.070, t=2.939, P<0.01, FDR adjusted). Conclusion:The sensorimotor network of patients with BD-Ⅰ has abnormal functional connections within and between networks, and FC values in some networks are positively correlated with manic symptoms, which may be part of the neural mechanisms of patients with BD-Ⅰ.

Glypican-3 (GPC3) is a key member of Glypican family and plays an important role in the development, angiogenesis and metastasis of hepatocellular carcinoma (HCC). Most HCC overexpresses GPC3, but GPC3 is hardly detected in normal adult liver and benign liver lesions, so it is regarded as a highly specific diagnostic marker and an ideal therapeutic target for HCC. In this study, we cloned the heavy and light chain variable region gene from the monoclonal antibody targeted to GPC3 screened in the previous stage, and linked it with a segment of flexible peptide (Linker) to obtain the single chain antibody against GPC3. The single chain antibody gene was cloned into vector for prokaryotic expression and purified to obtain high purity protein. Detection shows that the single-chain antibody produced by us has the same binding activity with the full-length antibody, and can accurately target the tumor site of Huh7 tumor-bearing model mice after coupling Cy5.5 fluorescence, suggesting that the single-chain antibody has the potential to realize multi-directional liver cancer precise surgical navigation under the guidance of a probe.
Animals ; Antibodies, Monoclonal ; Carcinoma, Hepatocellular/genetics* ; Glypicans/genetics* ; Liver Neoplasms/diagnosis* ; Mice

Claudin proteins are the most crucial components of tight junctions, and play an essential role in maintaining cell polarity, regulating cell permeability and the intercellular ion. In recent years, many studies have shown that abnormality of claudins expression is implicated in the tumor progression. The expression correlates with tumor prognosis and can serve as a biomarker of prognosis and potential therapeutic targets. This review summarizes the current knowledge regarding claudin dysregulation in cancer and highlights the progress in claudin-based treatments.
Claudins ; therapeutic use ; Enterotoxins ; Humans ; Neoplasms ; drug therapy ; Tight Junctions

Objective To investigate glycemic control,changes of inflammatory factors and their clinical significance in severe sepsis patients.Methods One hundred and three severe sepsis patients with abnormal hyperglycemia were randomly divided into the two groups and receive intensive insulin therapy (IIT) and conventional insulin therapy (CIT) respectively.According to glycosylated hemoglobin level,the two groups were further divided into stress hyperglycaemia and diabetes mellitus subgroups.The mortality and incidence of hypoglycemia were compared between the groups and subgroups.Enzyme linked immunosorbent assay was used to detect TNF-α,IL-6 levels before treatment,3 and 7 days after treatment.Results In IIT group,the mortality in diabetes mellitus subgroup was significantly higher than that in stress hyperglycaemia subgroup (66.7％ vs.30.8％,P ＜ 0.05),while the mortality in stress hyperglycaemia subgroup significantly higher than that in diabetes mellitus subgroup (54.1％ vs.25.0％,P ＜ 0.05) in CIT group.Multivariate Logistic regression analysis revealed IIT increased the risk for death in diabetes mellitus subgroup (OR =1.221,95％ CI:1.075-1.434),while decreased the risk for death in stress hyperglycaemia subgroup (OR =0.872,95％ CI:0.714-0.975).The incidence of hypoglycemia was significantly higher in IIT group than that in CIT group (13.7％ vs.1.9％,P ＜0.05).Before treatment,the levels of TNF-α,IL-6 in stress hyperglycaemia patients were significantly higher than those in diabetes mellitus patients.After 7 day treatment,The levels of TNF-α,IL-6 decreased significantly in stress hyperglycaemia patients (P ＜ 0.01),and decreased more significantly in IIT group than that in CIT group.Conclusion Severe sepsis patients with stress hyperglycaemia can attain better glycemia control and inhibition of inflammatory factors,and clinical benefit from IIT.