Objective To investigate the effect of programmed cell death-ligand 1(PD-L1)monoclonal antibody and paclitaxel(PTX)combined with lentinan(LNT)on human breast cancer MDA-MB-231 cells in vitro.Methods MDA-MB-231 cells,human peripheral blood mononuclear cells(PBMCs),and MDA-MB-231+PBMCs co-culture were randomly divided into control group,PTX group,LNT group,MPDL3280A(PD-L1 monoclonal antibody)group,PTX+LNT group,and PTX+LNT+MPDL3280A group.The cell activity was detected by CCK8.The expressions of MHC-I and PD-L1 were detected by flow cytometry.The levels of IFN-γ and TNF-α were detected by ELISA kits.Results Compared with control group,the activity of MDA-MB-231 cells was significant inhibited in PTX group,MPDL3280A group,PTX+LNT group,and PTX+LNT+MPDL3280A group(P＜0.01).LNT group and PTX+LNT+MPDL3280A group significantly promoted the immune effect of PBMCs(P＜0.05,P＜0.01).PTX+LNT+MPDL3280A group significantly inhibited the activity of MDA-MB-231cells co-cultured with PBMCs(0.56±0.16 vs.0.39±0.13,P＜0.05).Compared with the negative control,LNT significantly promoted the expression of PD-L1 in MDA-MB-231 and the secretion of IFN-γ by PBMCs(P＜0.05).Conclusion By blocking the effect between PD-L1 and PD-1,PD-L1 monoclonal antibody can improve immunity and promote the antitumor effect of PTX combined with LNT in vitro.

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

The inflammatory status in patients with chronic kidney disease(CKD)is closely associated with cardiovascular events,infections,and other complications,and is a powerful indicator for prognosis assessment.The core view of the"gut-kidney axis"theory reveals the relationship among inflammatory state,microbiota dysbiosis,and deterioration of renal function.The microbiota alters the microenvironment through structural changes and metabolites with different properties,subsequently leading to microbiota translocation,inducing inflammatory lesions,and damaging the kidneys.Recent studies have proposed that targeted microbiota intervention strategies such as probiotics,prebiotics,and synbiotics can modulate the microbiota structure,regulate the microenvironment,relieve renal inflammation,and affect the progression of renal disease,representing a potentially promising research direction in the future.This review discusses the characteristics of how intestinal microbiota influence the inflammatory status in CKD,focusing on the research progress of targeted microbiota intervention,aiming to discuss the effectiveness and scientific basis of these strategies,providing a foundation for the treatment of CKD and the expansion of targeted microbiota research,as well as offering references for the clinical application of probiotics,prebiotics,and synbiotics.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Objective To investigate the effect of programmed cell death-ligand 1(PD-L1)monoclonal antibody and paclitaxel(PTX)combined with lentinan(LNT)on human breast cancer MDA-MB-231 cells in vitro.Methods MDA-MB-231 cells,human peripheral blood mononuclear cells(PBMCs),and MDA-MB-231+PBMCs co-culture were randomly divided into control group,PTX group,LNT group,MPDL3280A(PD-L1 monoclonal antibody)group,PTX+LNT group,and PTX+LNT+MPDL3280A group.The cell activity was detected by CCK8.The expressions of MHC-I and PD-L1 were detected by flow cytometry.The levels of IFN-γ and TNF-α were detected by ELISA kits.Results Compared with control group,the activity of MDA-MB-231 cells was significant inhibited in PTX group,MPDL3280A group,PTX+LNT group,and PTX+LNT+MPDL3280A group(P＜0.01).LNT group and PTX+LNT+MPDL3280A group significantly promoted the immune effect of PBMCs(P＜0.05,P＜0.01).PTX+LNT+MPDL3280A group significantly inhibited the activity of MDA-MB-231cells co-cultured with PBMCs(0.56±0.16 vs.0.39±0.13,P＜0.05).Compared with the negative control,LNT significantly promoted the expression of PD-L1 in MDA-MB-231 and the secretion of IFN-γ by PBMCs(P＜0.05).Conclusion By blocking the effect between PD-L1 and PD-1,PD-L1 monoclonal antibody can improve immunity and promote the antitumor effect of PTX combined with LNT in vitro.

Objective:To study the effects of applying the think-pair-share (TPS) method combined with the microlecture teaching model in nursing teaching of general surgery.Methods:We assigned 48 nursing students interning in the department of general surgery of The First Affiliated Hospital of Air Force Medical University from August 2020 to August 2021 into control group to receive traditional teaching and 48 nursing students who interned from September 2021 to August 2022 into observation group to receive TPS+microlecture teaching. The two groups were compared in terms of test results, critical thinking abilities, post competencies, and satisfaction with teaching. SPSS 22.0 was used to perform the t test and chi-square test. Results:The observation group showed a significantly higher theoretical score [(93.21±4.34) vs. (88.65±3.69)], a significantly higher basic nursing skills score [(94.21±3.85) vs. (89.45±5.47)], and a significantly higher specialized skills score [(90.76±4.59) vs. (88.96±3.63)] than the control group ( P<0.05). The total score of the critical thinking ability scale and the scores of individual dimensions were significantly increased after training for both groups, and all the scores were significantly higher in the observation group than in the control group ( P<0.05). Both groups had significant improvements in the total and individual scores of post competencies after training, and the observation group had significantly higher scores than the control group ( P<0.05). Compared with the control group, the observation group had significantly higher proportions of students feeling satisfied with teaching, in terms of all evaluation items and also overall ( P<0.05). Conclusions:Applying the TPS+microlecture teaching model in general surgery nursing teaching can help nursing students improve theoretical and practical levels, critical thinking abilities, and post competencies, also with a high level of satisfaction with teaching.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear. OBJECTIVES: To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was designed as a multicenter, assessor-blind, randomized controlled trial. Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group. The treatment group received individualized TCM non-drug measures in combination with prone position ventilation, while the control group received prone position ventilation only for 5 consecutive days. MAIN OUTCOME MEASURES: The primary outcome measures were the percentage of patients with improved oxygen saturation (SpO₂) at the end of the 5-day intervention, as well as changes of patients' respiratory rates. The secondary outcome measures included changes in SpO₂ and total score on the self-made respiratory symptom scale. The improvement rate, defined as a 3-day consecutive increase in SpO₂, the duration of prone positioning, and adverse events were recorded as well. RESULTS: Among the 198 patients included in the intention-to-treat analysis, 159 (80.3%) completed all assessments on day 5, and 39 (19.7%) patients withdrew from the study. At the end of the intervention, 71 (91%) patients in the treatment group had SpO₂ above 93%, while 61 (75.3%) in the control group reached this level. The proportion of participant with improved SpO₂ was significantly greater in the intervention group (mean difference [MD] = 15.7; 95% confidence interval [CI]: 4.4, 27.1; P = 0.008). Compared to the baseline, with daily treatment there were significant daily decreases in respiratory rates in both groups, but no statistical differences between groups were found (all P ≥ 0.05). Compared to the control group, the respiratory-related symptoms score was lower among patients in the treatment group (MD = -1.7; 95% CI: -2.8, -0.5; P = 0.008) after day 3 of treatment. A gradual decrease in the total scores of both groups was also observed. Thirty-one adverse events occurred during the intervention, and 2 patients were transferred to the intensive care unit due to deterioration of their illness. CONCLUSION: TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19. The combined therapy significantly increased SpO₂ and improved symptom scores compared to prone positioning alone, thus improving the patients' respiratory function to help them recover. However, the improvement rate did not differ between the two groups. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR2300068319). Please cite this article as: Yin X, Jin Z, Li F, Huang L, Hu YM, Zhu BC, Wang ZQ, Li XY, Li JP, Lao LX, Mi YQ, Xu SF. Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial. J Integr Med. 2024; 22(6): 637-644.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Acupuncture Therapy/methods* ; China ; COVID-19/complications* ; Medicine, Chinese Traditional/methods* ; Moxibustion/methods* ; Oxygen Saturation ; Prone Position ; Respiration, Artificial ; Treatment Outcome

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.