The study aimed to construct the second and third generation chimeric antigen receptor T cells (CAR-T) targeting the c-mesenchymal-epithelial transition factor (c-Met) protein, and observe their killing effect on human serous ovarian cancer cell SKOV-3. The expression of MET gene in ovarian serous cystadenocarcinoma, the correlation between MET gene expression and the abundance of immune cell infiltration, and the effect of MET gene expression on the tissue function of ovarian serous cystadenocarcinoma were analyzed by bioinformatics. The expression of c-Met in ovarian cancer tissues and adjacent tissues was detected by immunohistochemical staining. The second and third generation c-Met CAR-T cells, namely c-Met CAR-T(2G/3G), were prepared by lentivirus infection, and the cell subsets and infection efficiency were detected by flow cytometry. Using CD19 CAR-T and activated T cells as control groups and A2780 cells with c-Met negative expression as Non target groups, the kill efficiency on SKOV-3 cells with c-Met positive expression, cytokine release and cell proliferation of c-Met CAR-T(2G/3G) were explored by lactate dehydrogenase (LDH) release, ELISA and CCK-8 respectively. The results showed that MET gene expression was significantly up-regulated in ovarian cancer tissues compared with normal tissues, which was consistent with the immunohistochemistry results. However, in all pathological stages, there was no obvious difference in MET expression and no correlation between MET gene expression and the race and age of ovarian cancer patients. The second generation and third generation c-Met CAR-T cells were successfully constructed. After lentivirus infection, the proportion of CD8⁺ T cells in c-Met CAR-T(2G) was upregulated, while there was no significant change in the cell subsets of c-Met CAR-T(3G). The LDH release experiment showed that the kill efficiency of c-Met CAR-T(2G/3G) on SKOV-3 increased with the increase of effect-target ratio. When the effect-target ratio was 20:1, the kill efficiency of c-Met CAR-T(2G) reached (42.02 ± 5.17)% (P < 0.05), and the kill efficiency of c-Met CAR-T(3G) reached (51.40 ± 2.71)% (P < 0.05). ELISA results showed that c-Met CAR-T released more cytokine compared to CD19 CAR-T and activated T cells (P < 0.05). Moreover, the cytokine release of c-Met CAR-T(3G) was higher than c-Met CAR-T(2G) (P < 0.01). The CCK-8 results showed that after 48 h, the cell number of c-Met CAR-T(2G) was higher than that of c-Met CAR-T(3G) (P < 0.01). In conclusion, both the second and third generation c-Met CAR-T can target and kill c-Met-positive SKOV-3 cells, with no significant difference. c-Met CAR-T(2G) has stronger proliferative ability, and c-Met CAR-T(3G) releases more cytokines.
Humans ; Female ; Ovarian Neoplasms/immunology* ; Proto-Oncogene Proteins c-met/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Cell Line, Tumor ; Cystadenocarcinoma, Serous/immunology* ; T-Lymphocytes/immunology*

PURPOSE: Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO₂) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO₂ (ΔScvO₂) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors. METHODS: In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase in cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO₂ and its change before and after fluid challenge. The Shapiro-Wilk test was used for the normality of continuous data. Data comparison between fluid responders and non-responders was conducted using a two-tailed Student t-test, Mann Whitney U test, and Chi-square test. Paired t-tests were used for normally distributed data, while the Wilcoxon signed-rank test was used for skewed data, to compare data before and after fluid challenge. RESULTS: Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO₂ (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO₂, with R² = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO₂ (R² = 0.245, p < 0.001). ΔScvO₂ had a good discriminatory ability for the responders and non-responders with a threshold of 4.4% (area under the curve = 0.732, p = 0.006). CONCLUSION ΔScvO₂ served as a reliable surrogate marker for ΔCI and could be utilized to assess fluid responsiveness, given that the change in CI was the sole contributing factor to the ΔScvO₂. In stable hemoglobin conditions, the absolute value of ScvO₂ could serve as a monitoring indicator for adequate oxygen delivery independent of oxygen consumption.
Humans ; Shock, Septic/blood* ; Male ; Female ; Middle Aged ; Prospective Studies ; Oxygen Saturation ; Aged ; Fluid Therapy ; Oxygen/blood* ; Oxygen Consumption ; Adult

ObjectiveNon-invasive magnetic stimulation technology has been widely used in the treatment of Alzheimer’s disease (AD), but there is a lack of convenient and timely methods for evaluating and providing feedback on the effectiveness of the stimulation, which can be used to guide the adjustment of the stimulation protocol. This study aims to explore the possibility of heart rate variability (HRV) in diagnosing AD and guiding AD magnetic stimulation intervention techniques. MethodsIn this study, we used a 40 Hz, 10 mT pulsed magnetic field to expose AD mouse models to whole-body exposure for 18 d, and detected the behavioral and electroencephalographic signals before and after exposure, as well as the instant electrocardiographic signals after exposure every day. ResultsUsing one-way ANOVA and Pearson correlation coefficient analysis, we found that some HRV indicators could identify AD mouse models as accurately as behavioral and electroencephalogram(EEG) changes (P<0.05) and significantly distinguish the severity of the disease (P<0.05), including rMSSD, pNN6, LF/HF, SD1/SD2, and entropy arrangement. These HRV indicators showed good correlation and statistical significance with behavioral and EEG changes (r>0.3, P<0.05); HRV indicators were significantly modulated by the magnetic field exposure before and after the exposure, both of which were observed in the continuous changes of electrocardiogram (ECG) (P<0.05), and the trend of the stimulation effect was more accurately observed in the continuous changes of ECG. ConclusionHRV can accurately reflect the pathophysiological changes and disease degree, quickly evaluate the effect of magnetic stimulation, and has the potential to guide the pattern of magnetic exposure, providing a new idea for the study of personalized electromagnetic neuroregulation technology for brain diseases.

Objective:To explore the short-term effect of drug-coated balloon angioplasty (DCBA) and common plain old balloon angioplasty (POBA) in the isolated popliteal artery chronic total occlusion (CTO), and to analyze the factors affecting the postoperative primary patency rate.Methods:A retrospective cohort study approach was used in this study. A total of 42 isolated popliteal CTO patients admitted to the First Affiliated Hospital of Bengbu Medical University from January 2020 to June 2022 were divided into two groups according to their different balloons: 24 as POBA group and 18 as DCBA group. The primary patency rate of target lesions, the clinically-driven target lesion revascularization(CD-TLR) rate, amputation and toe amputation rate, and the improvement of ankle-brachial index (ABI) and Rutherford grade at 6 and 12 months after surgery were compared.Measurement data with normal distribution was expressed as xˉ± s and means between two groups were compared using independent samples t-test. The percentage of counting data was calculated, and the rate between groups was compared by χ2 test or Fisher's exact probability method. Kaplan-Meier survival curve method was used to plot the survival curves of primary patency rate and CD-TLR free rate at 12 months after surgery, and Log rank test was used to compare the differences between groups . Univariate log rank test and multivariate Cox regression was used to analyze the factors affecting the primary patency rate at 12 months in patients with isolated popliteal CTO. Results:12 months after surgery, 4 patients in the DCBA group experienced lumen restenosis or occlusion while 12 patients in the POBA group experienced lumen restenosis or occlusion. The cumulative primary patency rate of target lesions in the DCBA group was higher than that in the POBA group (Log-rank χ2=4.03, P=0.045). ABI in the DCBA group at 6 and 12 months was greater than that in the POBA group [(0.91±0.11) vs (0.83±0.09), (0.84±0.11) vs (0.70±0.12), t=2.40, P=0.021, t=3.64 and P=0.001].There were no significant difference in cumulative CD-TLR exemption, amputation and amputation at 12 months, and Rutherford grade at 6 and 12 months for both groups(all P>0.05). The results of univariate analysis showed that DCBA as surgical method, hypertension and coronary heart disease were the influencing factors of the primary patency rate after chronic occlusion of the isolated popliteal artery (all P<0.05). The results of multivariate Cox regression analysis indicated that DCBA as surgical method was a protective factor for primary patency at 12 months (odds ratio =0.31,95% confidence interval: 0.10~0.870., P=0.038), while hypertension was an independent risk factor( OR=5.63,95% confidence interval: 1.54~20.56, P=0.009). Conclusions:The cumulative primary patency rate of target lesions 12 months after isolated popliteal CTO was higher than that of POBA. DCBA as surgical method was a protective factor for primary patency rate 12 months in patients with isolated popliteal CTO, while hypertension was an independent risk factor.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

To investigate the clinical utilization of Rituximab biosimilar (Rituximab injection) in order to provide references for evaluating its rationality and economic value in clinical application.

Objective:To evaluate the efficacy and safety of transdermal delivery of compound glycyrrhizin injection as an adjunctive treatment for erythematotelangiectatic rosacea (ETR).Methods:This was a randomized controlled trial conducted from March to October 2024. At Sichuan Provincial People′s Hospital, 60 patients with newly diagnosed ETR were prospectively enrolled and randomized by a random number table into study group [ n=30; 6 male and 24 female; aged 18-60 (38.9±9.8) years] and control group [ n=30; 4 male and 26 female; aged 18-60 (35.7±10.1) years]. The study group received transdermal delivery of compound glycyrrhizin injection by a medium-frequency drug-delivery therapeutic apparatus together with oral azithromycin and hydroxychloroquine sulfate, whereas the control group received oral azithromycin and hydroxychloroquine sulfate. The efficacy evaluations were conducted at baseline and at weeks 2, 4, 6, and 8 post-treatment. Outcome measures included percentage of erythema area, stratum corneum hydration, transepidermal water loss (TEWL), clinician′s erythema assessment (CEA), erythema and telangiectasia scores, dermatology life quality index (DLQI), and efficacy rate. Adverse reactions during treatment were also recorded. Results:Compared with baseline, both groups exhibited significant reductions in percentage of erythema area, TEWL, CEA, erythema and telangiectasia score, and DLQI, and significant increases in stratum corneum hydration at each post-treatment time point (all P<0.05). After 2, 4, 6, and 8 weeks of treatment, the percentage of erythema area, erythema and telangiectasia scores in the study group were all lower than those in the control group, while the stratum corneum hydration level in the study group was higher than that in the control group (all P<0.05). After 4, 6, and 8 weeks of treatment, TEWL, CEA, and DLQI in the study group were all lower than those in the control group (all P<0.05). After 4 weeks of treatment, the efficacy rate in the study group was 56.7% (17/30), which was higher than that of the control group at 23.3% (7/30, P=0.046). After 6 weeks of treatment, the efficacy rate in the study group was 83.3% (25/30), higher than that of the control group at 50.0% (15/30, P=0.020). After 8 weeks of treatment, the efficacy rate in the study group was 86.7% (26/30), higher than that of the control group at 66.7% (20/30, P<0.001). No severe adverse reactions were observed in either group. Conclusion:Transdermal delivery of compound glycyrrhizin injection as an adjunctive treatment for ETR demonstrates favorable efficacy and good safety.

Objective To analyze the developmental trends and research hotspots of anoikis in cancer research from 2005 to 2024.Methods Relevant literature was retrieved from the Web of Sci-ence Core Collection.Visualization tools including CiteSpace,VOSviewer and SCImago Graphica were employed to analyze publication volume,countries,institutions,authors,journals,keywords and other bibliometric indicators.Results A total of 2,252 articles were included in this study,showing an overall upward trend in publication volume,with a notable increase after 2012.China and the United States ranked highest in terms of publication volume and citation frequency.Representative institutions included Shanghai Jiao Tong University,Chulalongkorn University and MD Anderson Cancer Center,while a representative scholar was CHANVORACHOTE Pithi.The core journal was Oncogene.Keyword and co-citation analyses revealed that research focused on genetic characteristics,cancer treatment,prognostic prediction and metabolic reprogramming,with core terms including"ex-pression""metastasis"and"anoikis".Conclusion Research interest in the field of anoikis contin-ues to rise,with future directions focusing on drug resistance mechanisms,the tumor microenvironment,immunotherapy,signaling pathways and epithelial-mesenchymal transition(EMT).