Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer. Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were selected.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARHGAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the patients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expression.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups. Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue (P<0.001).The expression level of ARHGAP8 was correlated with tumor stage (P=0.024),lymph node metastasis (P=0.007),and age (P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P<0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P=0.011).The expression of ARHGAP8 was correlated with tumor size (P=0.010) and pathological stage (P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 patients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91% (29/44) patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy (P<0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86%,which was higher than that (53.33%) in the patients with high protein level of ARHGAP8 (P=0.033). Conclusion ARHGAP8 is highly expressed in the rectal cancer tissue.The patients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and development of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.
目的 分析ARHGAP8对中低位局部进展期直肠癌新辅助化疗疗效预测的敏感性,为进展期直肠癌的治疗提供精准依据。方法 通过生物信息学分析筛选,获得差异基因ARHGAP8。选取68例原发性直肠癌患者的直肠癌组织及直肠组织标本,应用实时荧光定量PCR、Western blot和免疫组织化学方法分别对ARHGAP8的表达强度进行验证,并收集患者性别、年龄、分期、肿瘤大小、分化程度、病理类型等临床病理特征进行功能验证;选取44例行新辅助化疗的中低位局部进展期直肠癌患者,采用免疫组织化学方法检测新辅助化疗前后ARHGAP8的表达情况,分析ARHGAP8在新辅助化疗前后、不同疗效组之间的表达情况。结果 生物信息学结果显示,ARHGAP8在癌组织及直肠组织中的表达差异有统计学意义(P<0.001),且ARHGAP8的表达水平与肿瘤分期(P=0.024)、淋巴结转移(P=0.007)、年龄(P=0.005)等临床特征相关。 实时荧光定量PCR结果显示,ARHGAP8 mRNA在癌组织中的表达显著高于直肠组织(P<0.001);Western blot和免疫组织化学结果显示,ARHGAP8蛋白在癌组织中的表达显著高于直肠组织(P=0.011);ARHGAP8的表达与肿瘤大小(P=0.010)、病理分期(P=0.005)密切相关,而与肿瘤分化程度、淋巴结转移、肝转移、Ki-67、微卫星不稳定性的表达程度无相关性。44例接受新辅助化疗的患者中TRG 0级13例、1级8例、2级8例、3级15例,其中65.91%(29/44)的患者新辅助化疗有效,新辅助化疗有效患者治疗后ARHGAP8的表达显著下降(P<0.001),ARHGAP8蛋白低表达患者的有效率为92.86%,显著高于ARHGAP8蛋白高表达者(53.33%)(P=0.033)。结论 ARHGAP8在直肠癌组织中高表达,ARHGAP8低表达的中低位局部进展期直肠癌患者对XELOX方案新辅助化疗更为敏感,ARHGAP8可作为直肠癌发生发展的潜在生物学指标,同时可作为中低位局部进展期直肠癌XELOX方案新辅助化疗疗效评估的重要参考指标。.

OBJECTIVE: To develop and validate a novel method for quantifying the efficacy of Bevacizumab (Bev) in treating Recurrent Respiratory Papillomatosis (RRP), and to evaluate the clinical outcomes of a three-dose Bev induction therapy followed by surgical intervention.
METHODS: Twenty-one RRP patients treated with a three-dose Bev regimen were included. A novel efficacy evaluation method using ImageJ software was developed to calculate the standardized lesion volume from laryngoscopic images. This was compared with the Derkay score. Clinical outcomes, including reduction rate, cumulative reduction rate, efficacy grading, recurrence, and adverse reactions, were analyzed.
RESULTS: In the study cohort, the reduction rate was significantly higher after the first treatment compared with subsequent treatments. The overall response rate increased from 75% after the first treatment to 100% after the third. Among patients with localized lesions who underwent surgery, 76% experienced recurrence with a mean recurrence time of 114.23 days. Most recurrent lesions were smaller than at baseline. Adverse reactions included increased blood pressure in seven patients, which resolved without intervention. The new method showed a significant positive correlation with the Derkay score.
CONCLUSIONS: In conclusion, based on the above findings, systemic Bev treatment for RRP is a safe and effective therapeutic approach, though further research is needed. Moreover, the new efficacy evaluation method we developed can significantly aid in studying the effectiveness of Bev treatment for RRP.
METHODS: 2 Laryngoscope, 2024.

BACKGROUND: We aimed to assess real-world efficacy of the PARP inhibitor, olaparib, in US Veterans with metastatic prostate cancer (mPC) by leveraging the national data repository and evaluate a novel approach to assess treatment efficacy in tumors considered rare or harboring rare mutations.
METHODS: Included Veterans had 1) mPC with somatic or germline alterations/mutations in genes involved in homologous recombination repair (HRR), 2) received olaparib monotherapy as well as a novel hormonal therapy/androgen receptor pathway inhibitors (NHT/ARPI), and/or chemotherapy, and 3) estimable rates of tumor growth (g-rate) using PSA values obtained while receiving treatment. Previous work has shown an excellent inverse correlation of g-rate with survival. Using g-rate, we determined tumor doubling time (DT) and DT ratios (DT on olaparib/DT on prior medication). We postulated that a DT ratio≥ 1 was associated with benefit.
RESULTS: We identified 139 Veterans, including 42 Black males with tumors harboring mutations/alterations in HRR genes who received olaparib: BRCA2 (50), ATM (32), BRCA1 (10), other mutations (47). 62/139 (45%) of all and 21/42 (50%) of Black Veterans had DT ratios ≥1, including 31, 10, 2, and 19 with BRCA2, ATM, BRCA1, and other mutations, respectively (p = 0.006). Median survival with DT ratios ≥1 was superior, being 24.5 vs. 11.4 months for DT ratio <1 (p = 0.01, HR 0.50, 95% CI 0.29-0.85). Benefit from olaparib, defined as DT ratio ≥1, was not observed for germline status, starting PSA value, number of prior therapies, or immediate prior therapy. Compared to matched cohorts, tumors in the olaparib cohort had shorter DTs with enzalutamide in first line (367 vs. 884 days; p = 0.0043).
CONCLUSIONS: Using equations indifferent to timing of assessments ideal for real-world efficacy analyses, we showed DT ratio ≥1 representing slower tumor growth on olaparib relative to the prior therapy correlates with improved survival. Olaparib efficacy in Veterans with mPC harboring mutations/alterations in HRR genes emulates clinical trial results. Black men had comparable results. Compared to matched cohorts, in first line, enzalutamide was less efficacious in tumors harboring mutations/alterations in HRR genes.
BACKGROUND: American Society of Clinical Oncology Conquer Cancer Foundation (ASCO CCF), the Blavatnik Family Foundation and the Prostate Cancer Foundation (PCF).

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and onset of the coronavirus disease-19 (COVID-19) pandemic led to an immediate need for therapeutic treatment options. Therapeutic antibodies were developed to fill a gap when traditional antivirals were not available. In late 2020, the United States Government undertook an effort to compare candidate therapeutic antibodies in virus neutralization assays and in the hamster model of SARS-CoV-2 infection. With the emergence of SARS-CoV-2 variants, the effort expanded to evaluate the efficacy of nearly 50 products against major variants. A subset of products was further evaluated for therapeutic efficacy in hamsters. Here we report results of the hamster studies, including pathogenicity with multiple variants, neutralization capacity of products, and efficacy testing of products against Delta and Omicron variants. These studies demonstrate the loss of efficacy of early products with variant emergence and support the use of the hamster model for evaluating therapeutics.

BACKGROUND: Cognitive-behavioral therapy (CBT) and habit reversal training (HRT) have shown application potential in addressing tic symptoms and comorbid psychiatric conditions. Despite their theoretical potential, empirical evidence on their combined efficacy remains limited.
OBJECTIVE: To evaluate the efficacy of CBT combined with HRT on anxiety disorders in children with Tourette\'s syndrome (TS).
METHODS: Clinical data of children with TS admitted to our hospital from January 2022 to June 2023 were collected, and the patients were grouped into the conventional therapy (control) group and the CBT combined with HRT group. Baseline characteristics, anxiety scores, tic severity scores, treatment adherence, and parental satisfaction were assessed. Statistical analysis was performed using t-tests, chi-square tests, and correlation analysis.
RESULTS: A total of 136 patients, including 65 patients in the control group and 71 patients in the CBT combined with HRT group, were included. The CBT combined with HRT group showed remarkable improvements compared with the control group. Post-intervention assessment revealed a decrease in anxiety scores from 63.52 ± 1.81 to 40.53 ± 1.64 (t = 2.022, P = 0.045), and the Yale Global Tic Severity Scale total score decreased from 22.14 ± 5.67 to 16.28 ± 4.91 (t = 2.288, P = 0.024). Treatment adherence was significantly higher in the CBT combined with HRT group (85.47 ± 7.62%) compared with the control group (82.32 ± 6.54%; t = 2.596, P = 0.010). Parental satisfaction scores were also higher in the CBT combined with HRT group (8.69 ± 1.77) compared with the control group (7.87 ± 1.92; t = 2.592, P = 0.011).
CONCLUSIONS: This study demonstrates that CBT combined with HRT significantly reduces anxiety symptoms and tic severity in children with TS, with higher treatment adherence and parental satisfaction. These findings support the potential application of this comprehensive therapeutic approach for TS treatment.

Cancer immunotherapy is used to treat tumors by modulating the immune system. Although the anticancer efficacy of cancer immunotherapy has been evaluated prior to clinical trials, conventional in vivo animal and endpoint models inadequately replicate the intricate process of tumor elimination and reflect human-specific immune systems. Therefore, more sophisticated models that mimic the complex tumor-immune microenvironment must be employed to assess the effectiveness of immunotherapy. Additionally, using real-time imaging technology, a step-by-step evaluation can be applied, allowing for a more precise assessment of treatment efficacy. Here, an overview of the various imaging-based evaluation platforms recently developed for cancer immunotherapeutic applications is presented. Specifically, a fundamental technique is discussed for stably observing immune cell-based tumor cell killing using direct imaging, a microwell that reproduces a confined space for spatial observation, a droplet assay that facilitates cell-cell interactions, and a 3D microphysiological system that reconstructs the vascular environment. Furthermore, it is suggested that future evaluation platforms pursue more human-like immune systems.

There is a lack of effective therapeutic drugs for pulmonary arterial hypertension. Previous studies have demonstrated the positive cardiovascular system protective effects of the new peptide ACTY116. However, its stability in ordinary aqueous solution injections is poor and its half-life in the body is short, which has hindered the development of preparations. This study aimed to prepare in situ forming implants (ISFIs) of the peptide ACTY116 and investigate its impact on pulmonary arterial hypertension. We prepared ISFIs using NMP/TA as a solvent and PLGA as a polymer. These ISFIs exhibited low viscosity, low toxicity and sustained release properties. In a mouse model of pulmonary hypertension induced by SU5416/hypoxia, both ISFIs and ACTY116 peptides effectively reduced pulmonary hypertension, cardiac hypertrophy and pulmonary blood vessel wall thickness. In conclusion, this study highlights the potential of ACTY116 as a treatment for pulmonary arterial hypertension and suggests that incorporating it into an in-situ gel implant could be a promising option.

Traditional Chinese medicine(TCM) syndrome-based efficacy is an evaluation index which is unique to TCM and can reflect the advantages of TCM. The development of the methods and measurement tools for evaluating TCM syndrome-based efficacy can provide objective and quantitative evidence for the clinical efficacy evaluation of TCM and the development of new Chinese medicine preparations, being the exploration direction of innovative methods and technologies for evaluating TCM efficacy. The conventional evaluation methods are subjective and limited to the mitigation of symptoms and the improvement of physical signs, which make it difficult to form a unified evaluation standard. In addition, the evaluation methods lack unity, objectivity, and quantitative research. The scientific connotation, evaluation ideas and methods, and key technologies of the evaluation for the therapeutic effect on syndromes remain unclear, which leads to diverse evaluation modes, methods, and indexes. The syndrome-based efficacy scale provides a new idea for the objective quantification and standardization of TCM syndromes. This review systematically summarizes the methods and problems, introduces the research progress in the evaluation scales, and puts forward some thoughts on the characteristics of TCM syndrome-based efficacy evaluation, aiming to provide insights for the research in this field.

UNASSIGNED: This study assesses the efficacy of rituximab in the treatment of neuromyelitis optica spectrum disorders (NMOSD).
UNASSIGNED: The study initially included 40 patients with NMOSD diagnosed, after excluding patients who did not meet the complete inclusion criteria. Patients in the conventional group received routine clinical treatment, while patients in the study group received additional treatment with rituximab on the basis of the conventional treatment. Baseline data and clinically relevant indicators were collected for all patients, and the efficacy was compared between the two groups.
UNASSIGNED: Baseline data were comparable between the two groups (p > 0.05). The EDSS scores after clinical treatment in the study group were lower than those in the conventional group, and the difference in EDSS scores before and after treatment was higher than that in the conventional group (p < 0.05). The difference in visual acuity correction before and after treatment was not significant between the two groups (p > 0.05). Laboratory indicators in the study group after clinical treatment were superior to those in the conventional group (all p < 0.05). The recurrence rate after clinical treatment in the study group was significantly lower than that in the conventional group (p < 0.05). Adverse reactions after clinical treatment in the study group were less than those in the conventional group (p < 0.05).
UNASSIGNED: This study found that rituximab demonstrated significant efficacy in the acute attacks and recurrence prevention of NMOSD, emphasizing its relatively good safety and tolerability. It highlights the potential of rituximab in treating NMOSD and provides valuable insights for future disease management.

UNASSIGNED: Single-photon emission computed tomography (SPECT) ventilation perfusion imaging is the main imaging method for the diagnosis of pulmonary embolism, and its application in the diagnosis and efficacy evaluation of chronic thromboembolic pulmonary hypertension (CTEPH) has been paid more and more attention. In recent years, with the development of computer software technology, ventilation/perfusion (V/Q) imaging quantitative analysis technology has become more and more mature. The objective of this study was to investigate the utility of quantitative analysis of pulmonary V/Q scintigraphy in evaluating the efficacy of balloon pulmonary angioplasty (BPA) in patients with CTEPH.
UNASSIGNED: In this retrospective analysis, we collected data of patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital from April 2018 to September 2020. The sample consisted of 23 males and 28 females, with an average age of 55.1±12.7 years. All patients underwent V/Q scintigraphy within one week before surgery, and we reviewed the pulmonary angiography within 1-3 months following the last BPA procedure. We repeated V/Q scintigraphy within 1 week before or after the pulmonary angiography, at the time of collecting clinical and hemodynamic parameters of these patients. We divided the patients into two groups based on the presence of residual pulmonary hypertension post-surgery and compared the pre- and post-operative quantitative pulmonary perfusion defect percentage scores (PPDs%) using the t-test.
UNASSIGNED: In all, 102 V/Q scintigraphy scans were performed in 51 patients. The quantitative PPDs% were positively correlated with the hemodynamic indexes mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and mean right ventricular pressure (RVP) (r=0.605, 0.391, and 0.464, respectively, all P<0.001) and negatively correlated with the 6-minute walking distance (6MWD) (r=-0.254, P=0.010). The average preoperative quantitative PPDs% were (49.0±15.6)% which significantly decreased to (33.5±13.9)% after surgery (t=11.249, P<0.001). The preoperative quantitative PPDs% were (54.7±15.7)% and (44.0±13.8)% in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=2.599, P=0.012). The postoperative quantitative PPDs% were (41.5±12.5)% and (26.3±11.0)%, in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=4.647, P<0.001).
UNASSIGNED: In this study, we found that quantitative analysis of SPECT pulmonary V/Q scintigraphy adequately reflected the pulmonary artery pressure and clinical status in patients with CTEPH. Our results demonstrate its definite utility in predicting residual pulmonary hypertension and in evaluating the postoperative efficacy of BPA in patients with CTEPH.