Mesenchymal stem cells have emerged as a promising cell therapy for anti-tumor research due to their homing properties,low immunogenicity,anti-angiogenic activity,anti-inflammatory properties,and paracrine effects.Paclitaxel has been clinically used for over thirty years in the treatment of various tumors such as ovarian cancer,lung cancer,and breast cancer.However,the broad-spectrum anti-tumor properties of paclitaxel are not possessed by the aforementioned cell therapies.Moreover,its adverse reactions,including peripheral neuropathy,bone marrow suppression,and gastrointestinal reactions,have long plagued cancer patients.In recent years,many studies have focused on combining cell therapy with chemotherapy to achieve better treatment outcomes,giving rise to a new drug delivery system that utilizes mesenchymal stem cells as carriers for delivering chemotherapeutic drugs.This review summarizes the research progress in MSC-based drug delivery systems for paclitaxel.

Dysphagia is the main complication of chemoradiotherapy for head and neck cancer. Recently, the advancement of multidisciplinary treatment has achieved a higher tumor control rate, but also a higher incidence of late radiation-induced dysphagia in head and neck cancer. Radiation-induced dysphagia leads to prolonged unnatural feeding, nutritional deficiency, weight loss, and also has a major risk for silent aspiration and aspiration pneumonia, which significantly reduces the quality of life of patients. Besides, late radiation-induced dysphagia is the main reason for limiting the intensity of treatment. Therefore, it is of great significance to deeply understand the pathogenesis of radiation-induced dysphagia and actively explore effective prevention and treatment measures to improve the survival rate and quality of life in head and neck cancer. This paper summarizes the pathogenesis, occurrence, risk factors of radiation-induced dysphagia in head and neck cancer, as well as the progress in the measurement and reporting methods, prevention and treatment strategies.

Objective:To assess the effects of low temperature environment on skeletal and serum metabolites, and explore underlying mechanism.Methods:C57BL/6J mice were divided into normal temperature control group(control group) and intermittent low temperature exposure group(low temperature group). After 12 weeks of intervention, Micro-computed tomography(CT) was used to detect the bone microstructure. The mouse femur was stained by hematoxylin-eosin(HE) staining, tartrate-resistant acid phosphase(TRAP) staining, and type Ⅰ collagen staining. The serum metabolites were detected by liquid chromatography-mass spectrometry(LC-MS), comprehensive principal component analysis and random forest were used to identify potential biomarkers influencing bone metabolism in serum samples, and the metabolic pathways affecting bone metabolism were enriched through metabolic database analysis.Results:Micro-CT results showed that compared to the control group, the bone mineral density, bone volume/tissue volume, trabecular thickness, and trabecular number decreased(all P<0.05) in low temperature group of mice, while trabecular separation and bone surface/bone volume ratio increased(both P<0.05). The staining results of HE indicated that, compared with the control group, low temperature group exhibited disordered bone trabecular space structure, widened gaps, reduced unit area, and the presence of numerous adipose vacuoles. TRAP staining suggested that compared to the control group, low temperature group had an increased number of osteoclasts. The results of type Ⅰ collagen staining showed that the number of type Ⅰ collagen in the low temperature group was lower than that in the control group, and the structure was disordered. On the other hand, metabolomics identified 40 metabolites in serum, including deoxycholic acid, methionine, bilirubin, and salicylic acid, which are involved in lipid metabolism and amino acid metabolism. Conclusion:Low temperature leads to decreased bone mass, which may be related to the regulation of lipid metabolism and amino acid metabolism.

Cervical cancer (CC) has been a hot topic in the field of gynecological cancer due to its high morbidity and mortality. As one of the major components, tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment (TME), differentiating into M1 and M2 phenotypes under the influence of various cytokines, with a predominance of the M2 phenotype among TAMs. Notably, the functions of these two phenotypes are almost opposite. M1 macrophages promote inflammation and inhibit tumor development, while M2 macrophages tend to suppress the immune response and promote tumor growth. Additionally, TAMs can influence tumor invasion, metastasis and immune regulation through interacting with various lymphocytes and cytokines. Numerous studies have demonstrated that TAMs can be used as prognostic markers for CC, and as therapeutic targets in clinical setting. A deeper comprehension of interactions between TAMs and CC, achieved by integrating findings and conclusions from various studies, is conducive to the discovery of new directions for research and new perspectives for clinical treatment.
Humans ; Uterine Cervical Neoplasms/pathology* ; Female ; Tumor-Associated Macrophages/metabolism* ; Tumor Microenvironment/immunology* ; Disease Progression ; Cytokines/immunology* ; Animals ; Macrophages/immunology*

Alzheimer's disease (AD) is a neurodegenerative disorder with an insidious onset, primarily characterized by a progressive decline in cognitive function. MCP-1 is a cytokine with chemotactic effects on monocytes, which can regulate their migration and infiltration and participate in disease progression. Increasing evidence suggests that MCP-1 plays a key role in the progression of Alzheimer's disease and has the potential to act as an early diagnostic marker and intervention target. This paper reviews the regulatory role of MCP-1 in neuroinflammation, beta-amyloid (Aβ) deposition and Tau pathology, and explores the potential of MCP-1 as a biomarker and intervention target for the early diagnosis of Alzheimer's disease.
Alzheimer Disease/metabolism* ; Humans ; Chemokine CCL2/genetics* ; Amyloid beta-Peptides/metabolism* ; Animals ; tau Proteins/metabolism* ; Biomarkers/metabolism*

BACKGROUND: Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. METHODS: Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. RESULTS: In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons. CONCLUSIONS: Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.
Adult ; Humans ; BNT162 Vaccine ; 2019-nCoV Vaccine mRNA-1273 ; Network Meta-Analysis ; Immunization Schedule ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Viral Vaccines ; mRNA Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral

Objective:To perform cross-cultural adaption of the KING′s Parkinson′s Disease Pain Scale (KPPS), explore its reliability and validity in Chinese Parkinson′s disease (PD) patients, and to create the new version of the pain scale which adapts to the Chinese PD patients.Methods:This study enrolled 225 patients, including 121 men and 104 women who were selected from the Outpatient Center of Movement Disorders Clinic of the Second Affiliated Hospital of Soochow University from July 2018 to July 2020. All patients completed the evaluation of the Chinese Version of KPPS (KPPS-CV). According to the preliminary evaluation results, the expert group modified KPPS-CV after discussion, and developed a Modified KPPS-CV (MKPPS-CV). These patients then completed the MKPPS-CV evaluation during the 3-month follow-up. Cross-cultural adaptation was performed according to published international guidelines that include translation, back-translation, expert review, and pretesting. The following psychometric properties were evaluated: basic item analysis; floor and ceiling effects; construct validity; content validity; criterion validity (Spearman′s rho between the KPPS-CV and Numeric Rating Scale); internal consistency reliability (Cronbach′s alpha); test-retest reliability (intra-class correlation coefficient, ICC).Results:In item analysis, 50% of the items had poor discrimination (critical ratio<3.0), and floor effect was found in all domains (proportion of 0 point>15%). The items were reclassified after exploratory factor analysis. The content validity of item 3, item 10 and item 11 was low (item-level content validity index<0.78). Criterion validity showed the highest correlations (Spearman′s rho>0.88) between the KPPS-CV and Numeric Rating Scale. While overall scale reliability was minimally acceptable at 0.46, which showed a poor reliability of this scale. Test-retest reliability was excellent for each item (Spearman's rho>0.85). The Cronbach′s alpha of MKPPS-CV (0.76) was higher than that of KPPS-CV (0.46). It showed a great improvement after the modifying.Conclusions:When using scales that are not developed for local populations, differences in culture and clinical practices should be taken into account. MKPPS-CV is an acceptable, valid measure to evaluate pain in Chinese PD patients, which is more suitable for Chinese people.

Objective:To investigate the effects of early intervention with low-dose dobutamine on pneumonia complicated with sepsis.Methods:We retrospectively analyzed the clinical data of 200 patients with pneumonia complicated by sepsis who received treatment in the First People's Hospital of Taizhou from January 2015 to January 2018. We divided these patients into control and observation groups with 100 patients/group according to different treatment methods. The control group was treated with immunoglobulin and methylprednisolone and given ventilator-assisted ventilation. The observation group was given low-dose dobutamine based on the treatments given in the control group. Clinical efficacy, pulmonary function, the incidence of adverse reactions, length of hospital stay, time to dyspnea disappearance, organ failure rate, and mortality were compared between the two groups.Results:Total response rate was significantly higher in the observation group than in the control group [96.0% (96/100) vs. 77.0% (77/100), χ2 = 15.45, P < 0.05]. After treatment, improvements in the pulmonary function indexes [forced vital capacity, forced expiratory volume in one second, and forced expiratory volume in one second/forced vital capacity] in the observation group were superior compared with those in the control group ( t = -15.25, -34.56, -3.77, all P < 0.001). Length of hospital stay and time to dyspnea disappearance in the observation group were (4.23 ± 0.89) days and (3.21 ± 0.58) days, respectively, which were significantly shorter than those in the control group [(8.96 ± 1.58) days, (7.26 ± 0.24) days, t = -26.08, -64.52, both P < 0.001]. The incidence of adverse reactions, incidence of organ failure, and mortality in the observation group were 2.0% (2/100), 1.0% (1/100) and 2.0% (2/100) respectively, which were significantly lower than those in the control group [18.0% (18/100), 20.0% (20/100), 10.0% (10/100), χ2 = 16.80, 19.20, 5.67, all P < 0.05). Conclusion:Early intervention with low-dose dobutamine for the treatment of pneumonia complicated by sepsis can greatly improve clinical efficacy, reduce adverse reactions, decrease the incidence of organ failure and mortality, improve pulmonary function, and shorten the length of hospital stay and time to dyspnea disappearance.

Objective:Based on the modified ultracentrifugation method, the outer membrane vesicles (OMV) secreted by Klebsiella pneumoniae were rapidly separated, identified and quantified. Methods:Standard strains of classic Klebsiella Pneumoniae (cKP) purchased from the Clinical Laboratory Center of the National Health Commission, and hypervirulent Klebsiella pneumoniae (hvKP) which was donated by Taiwan University were cultured in M9 basal media for 9 hours, and the OMV were extracted by modified ultracentrifugation. The shape and size of OMV were identified by transmission electron microscopy (TEM), relative quantification by Stewart phospholipids analysis method. Two groups were compared using independent samples t test. Results:It was observed under the TEM that most of the OMV secreted by cKP and hvKP showed spherical vesicle structure and a small part were irregular. The diameter of OMV ranged from 20 to 250 nm, multiple vesicles could be seen in clusters. Relative quantification found that the number of OMV secreted by hvKP were more than cKP ( P<0.05). Conclusions:This study successfully achieved the extraction, identification and quantification of OMV from Klebsiella pneumoniae through the modified ultracentrifugation method, which provided a foundation for further study about the function and mechanism of OMV, and also provided new ideas for the treatment of bacteria. Based on the ultracentrifugation method, the OMV secreted by Klebsiella pneumoniae were rapidly separated and extracted, then identified and quantified.

Objective:To explore the effects of hospital-to-community model-based case management on outcomes and life quality of patients with atrial fibrillation.Methods:By convience sampling method, a total of 90 cases of atrial fibrillation patients admitted to Changzhou Second People′s Hospital from January 2019 to May 2020 were randomly divided into control group and experimental group, with 45 cases in each group. The patients in the control group received routine nursing care, the experimental group implemented hospital-to-community model-based case management. The beliefs about medicine, medication compliance, quality of life and readmissions of cardiovascular events were compared between 2 groups before and 6 months after intervention.Results:Finally, 41 cases were included in the experimental group and 38 cases in the control group. Before intervention, there were no significant differences in various indexes between the two groups ( P>0.05). After 6 months of intervention, the scores of specific-necessity in Beliefs about Medicines Questionnaire-Specific (BMQ-Specific) and Morisky Medication Adherence Scale-8 (MMAS-8) were (16.98 ± 4.22) and (7.15 ± 0.69) points in the experimental group, higher than in the control group (14.95 ± 4.33) and (6.32 ± 1.07) points; the scores of specific-concerns in BMQ-Specific were (6.83 ± 1.91)points in the experimental group, lower than in the control group (8.42 ± 2.73) points. The differences were statistically significant ( t = 2.11, 4.07, 2.98, all P<0.05); the scores of physical function, role-physical, pain, general health, mental health dimensions and total scores in SF-36 were (80.37 ± 3.46), (46.63 ± 14.54), (90.37 ± 5.78), (70.07 ± 9.98), (84.20 ± 8.73) and (584.88 ± 25.71) points in the experimental group, higher than in the control group (70.13 ± 11.20), (37.34 ± 10.25), (83.37 ± 6.89), (59.55 ± 7.98), (77.58 ± 9.09) and (533.87 ± 31.62) points, the differences were statistically significant ( t values were 3.30-7.89, all P<0.05). At 6 months after discharge, the re-admission of cardiovascular events were 5 cases (12.2%) in the experimental group and 12 cases (31.6%) in the control group, the difference was statistically significant ( χ2=4.74, P<0.05). Conclusions:Hospital-to-community model-based case management can effectively promote beliefs about medicine and medication compliance, improve quality of life and decrease re-admission of cardiovascular events of patients with atrial fibrillation.