OBJECTIVES: To evaluate the photothermal and antibacterial activities of polydopamine-modified phycocyanin nanoparticles (PDA@PC NPs) and their capacity for promoting wound healing. METHODS: PDA@PC NPs were synthesized from phycocyanin (C-PC) and dopamine hydrochloride using a one-pot method. The photothermal activity of the nanoparticles was assessed in vitro by 808 nm laser irradiation, their biocompatibility was evaluated using CCK-8 assay, and their photothermal antibacterial activity by plate colony counting. In adult male BALB/c mice, two symmetrical full-thickness skin wounds (1.0 cm ×1.0 cm) were created on both sides of the spine, and 200 μL of Staphylococcus aureus suspension was inoculated into the wounds. The mice were divided into control group, PDA@PC NPs group, and PDA@PC NPs with laser irradiation group, and wound healing rates and histomorphological changes in the wound tissues were evaluated on days 0, 7 and 14 after modeling. RESULTS: The synthesized PDA@PC NPs exhibited no obvious cytotoxicity up to a concentration of 500 μg/mL and showed strong photothermal and antibacterial activities in response to 808 nm laser irradiation. In the mouse models, the size of the infected skin wounds showed substantial reduction at 7 and 14 days in PDA@PC NPs group and PDA@PC NPs with laser irradiation group, and the mean wound healing rate was faster in the latter group. HE staining and Masson's trichrome staining revealed extensive granulation tissue formation and collagen deposition on the wound surfaces in both of the treatment groups, and these changes were more obvious in the PDA@PC NPs with laser irradiation group. CONCLUSIONS PDA@PC NPs possess excellent photothermal and antibacterial activities and can effectively promote wound healing in mice.
Animals ; Indoles/chemistry* ; Wound Healing/drug effects* ; Mice ; Mice, Inbred BALB C ; Male ; Nanoparticles ; Polymers/chemistry* ; Phycocyanin/chemistry* ; Skin/injuries* ; Staphylococcus aureus/drug effects* ; Anti-Bacterial Agents/pharmacology*

Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

Objective To isolate endophytic fungi from Angelica sinensis and evaluate the bioactivity of their secondary metabolites.Methods Angelica sinensis and rhizosphere soil were utilized as materials.The tissue homogenization method was employed with six diverse culture media to isolate endophytic fungi.The antibacterial activity of secondary metabolites was gauged using a 96-well plate assay,while UV spectrophotometry was used to evaluate the inhibitory activity of four enzymes.Results A total of 153 fungal strains were isolated and purified from Angelica sinensis roots,stems,leaves,and soil.The samples exhibited specific inhibitory activities against adenosine deaminase(ADA),β-lactamase,xanthine oxidase(XO),and tyrosinase(TYR),with rates of 45.83%,52.78%,51.39%and 55.56%,respectively.Furthermore,1.39%of the samples displayed wide-ranging inhibitory effects against four indicator bacteria.Strain 6B also showcased the lowest inhibitory concentration values of 62.5 and 7.81 μg/mL against Escherichia coli ATCC25922 and ATCC35218,respectively,signifying its potential research significance.Conclusion Angelica sinensis has abundant endophytic fungal resources and is a good source for discovering active compounds,demonstrating certain research value.

Objective To analyze the changes of liver and kidney function, blood glucose and lipid metabolism at different follow-up time points of different treatment regimens, and to provide reference for clinical optimization and adjustment of medication in HIV/AIDS patients. Methods The changes of liver and kidney function, blood glucose and lipid metabolism at seven follow-up time points were analyzed retrospectively. The baseline blood collection time of HIV /AIDS patients was set as the starting point, and the final follow-up time was set as the end point. The seven follow-up points were 0, 3, 6, 9, 12, 18 and 24 months respectively. Results There were statistically significant differences in the distribution of sex, age, education, marital status, WHO staging, infection route, and baseline CD4+T lymphocyte count among 605 enrolled patients based on different treatment regimens. Liver function: The level of T-Bil in group E was higher than that of baseline at 9M, 12M, 18M and 24M after treatment (P<0.01); In group F, the level of T-Bil was higher than that of baseline at 9M after treatment (P=0.001); The levels of ALT in group C at the six follow-up points after treatment were higher than the baseline (P<0.001); The level of AST in group C was higher than that of baseline after 3M and 6M treatment (P<0.05). Renal function: The level of UREA in group C was higher than that in baseline after 6M treatment (P=0.007); The level of UREA in group F was higher than that in the baseline after 12M treatment (P<0.001); The level of UA in group F was higher than that of baseline after 3M, 6M and 12M treatment (P<0.05). Blood lipid and blood glucose: The levels of Glu at some follow-up points after ART treatment in group A and group C were higher than that at baseline (P<0.05); The levels of TG at some follow-up points in group A, group E and group F after ART treatment were higher than those at baseline (P<0.05); The levels of TC at some follow-up points in group A, group B, group C, group E and group F after ART treatment were all higher than the baseline (P<0.05). Conclusion Regular monitoring of changes in laboratory indicators of different treatment regimens during ART is of great importance to the prognosis of patients. Different laboratory indicators should be monitored according to different treatment regimens to effectively prevent adverse reactions caused by different treatment regimens.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

Background Fluorine accumulates in the brain tissue after long-term excessive intake and subsequently cause nerve damage and decline of learning and memory ability. Receptor of advanced glycation end-products (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway is considered to be involved in the associated mechanism. Objective To study the changes of RAGE/ p38MAPK/ NF-κB signaling pathway in rats with subchronic fluorosis, and to explore the protective effects of extract of Ginkgo biloba 761 (EGb761) and RAGE antagonist (FPS-ZM1) on neuromemory ability. Methods Ninety male clean SD rats were divided into 9 groups with 10 rats in each group. The modeling period was 6 months. Control group (C group): free drinking tap water (fluoride content <0.5 mg·L⁻¹), low- and high-dose fluoride groups (LF group, HF group): free drinking tap water with 10 or 50 mg·L⁻¹ fluoride; intervention group of Ginkgo biloba extract (CE, LFE, and HFE groups): on the basis of the C group, LF group, and HF group, 100 mg·kg⁻¹·d⁻¹ EGb761 was given daily via intragastric administration; FPS-ZM1 intervention groups (CF, LFF, and HFF groups): 7 d before the end of modeling, 1 mg·kg⁻¹·d⁻¹ FPS-ZM1 was injected intraperitoneally daily on the basis of the C group, LF group, and HF group. The contents of fluoride in brain and blood of each group were detected. The learning and memory ability was tested by water maze experiment. The histopathologic changes of the hippocampus were detected by Nissl staining. The protein expression levels of RAGE and its ligand high mobility group protein B1 (HMGB1), NF-κB, p38MAPK, phospho-p38MAPK (p-p38MAPK), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in brain tissue were detected by Western blotting. The mRNA expression levels of RAGE, HMGB1, and p38MAPK were detected by quantitative real-time PCR. Results Compared with the C group, the contents of blood fluoride and brain fluoride in the LF and the HF groups were increased (P<0.05). The results of the water maze experiment showed that, compared with the C group, the escape latency time of the LF group and the HF group was longer and the crossing times were reduced; compared with the HF group, the escape latency time of the HFE group and the HFF group was shortened, and the crossing times were increased (P<0.05). The Nissl staining results showed that the number of Nissl body in the HF group decreased compared with the C group; compared with the HF group, the number of Nissl body in the HFE group and the HFF group increased. The Western blotting results showed that compared with the relative protein expression levels of RAGE, HMGB1, NF-κB, p38MAPK, p-p38MAPK, IL-6, and TNF-α in the C group , the levels of above indicators in the HF group and the levels of RAGE, HMGB1, NF-κB, p-p38MAPK, and IL-6 in the LF group were up-regulated (P<0.05); compared with the HF group, the levels of above indicators in the HFE group and the HFF group were all down-regulated (P<0.05); compared with the relative protein expression levels of RAGE and HMGB1 in the LF group, the levels in the LFE group and the LFF group were all down-regulated (P<0.05). The quantitative real-time PCR results showed that compared with the C group, the mRNA expression levels of RAGE and HMGB1 in the LF group and the HF group were up-regulated; compared with the LF group, the mRNA expression levels of RAGE in the LFE group and the LFF group were down-regulated ; compared with the HF group, the mRNA expression levels of RAGE and HMGB1 in the HFE group and the HFF group were down-regulated (P<0.05). Conclusion The central nervous system injury caused by subchronic fluorosis may be related to the activation of RAGE/p38-MAPK/NF-κB signaling pathway, which can impair the learning and memory ability of rats, while EGb761 and FPS-ZM1 may have certain protective effects on the nerve injury.

Objective:To investigate the clinical characteristics and prognosis of duodenal neuroendocrine neoplasms.Methods:The clinical data of 35 patients with duodenal neuroendocrine neoplasms admitted to Union Hospital, Tongji Medical College, Huazhong University of Science & Technology from Jan 2012 to Dec 2021 were retrospectively analyzed. The differences of clinical characteristics between periampullary and non-periampullary duodenal neuroendocrine neoplasms were analyzed. Kaplan-Meier curve was used for survival analysis, and the clinical factors affecting the prognosis were analyzed.Results:Of the 35 patients, 30 underwent tumor resection, 7 (23%) developed different degree of complications after operation and were improved and discharged after intervention. A total of 5 patients died during the follow-up period. Only 1 of 30 patients who underwent tumor resection died 30 months after operation due to disease progression, and the others had no recurrence or metastasis. Univariate analysis showed that tumor size, tumor grade, and tumor location were associated with the prognosis of patients (all P<0.05), and multivariate analysis showed that patients with tumors located.Away from the ampulla had a significantly better prognosis than those located around the duodenal ampulla ( P<0.01). Conclusions:Patients with duodenal neuroendocrine neoplasms have a good prognosis after complete resection; patients with duodenal neuroendocrine neoplasms located around the ampulla of Vater have a relatively poor prognosis compared with those away from the area of ampulla.

Objective:To study the characteristics of vaginal microbiota in pregnant women with premature rupture of membranes (PROM) and to establish prediction models for PROM.Methods:This study involved 35 women with preterm premature rupture of membranes (PPROM), 180 with term premature rupture of membranes (TPROM) and 255 term birth cases without premature rupture of membranes (TBWPROM, control group). The V3-V4 hypervariable region sequences in the vaginal samples collected at 16-28 weeks of gestation were detected by 16S rRNA gene next-generation sequencing. The differences in Alpha and Beta diversity, and the attributes and metabolic function prediction of each recognized species among the three groups were analyzed. Subsequently, a random forest model was used to establish the prediction models for PROM using vaginal microbiota species and environmental risk factors.Results:Compared with the control group, the Alpha diversity of the PPROM group was higher (Observed features, P=0.022; Faith_pd index, P=0.024) and Beta diversity was also significantly different (Unweighted UniFrac, P=0.010; Jaccard index, P=0.008). In PPROM cases, Megasphaera genomosp. typeⅠ was significantly increased ( P=0.017) and Lactobacillus mulieris was significantly decreased ( P=0.003). In the patients with TPROM, Megasphaera was significantly increased ( P=0.009) and Lactobacillus mulieris was significantly decreased ( P=0.002). In terms of functional pathways, sulfur oxidation ( P=0.021), methanogenesis from acetate ( P=0.036), L-histidine biosynthesis ( P=0.009), adenosylcobalamin biosynthesis ( P=0.041) and fucose degradation ( P=0.001) were significantly increased in patients with PPROM; L-histidine biosynthesis ( P<0.001) and fucose degradation ( P=0.030) were significantly increased in patients with TPROM. The prediction models were established using the random forest model with vaginal microbiota species and environmental risk factors and the prediction model for PPROM performed well [AUC: 0.739 (95%CI: 0.609-0.869), sensitivity: 0.928, specificity: 0.659, positive predictive value: 0.750, negative predictive value: 0.906], which had a certain reference value. Conclusions:Vaginal microbiota might be related to the development and progression of PROM. Studying the differences in vaginal microbiota might provide a new idea for the prevention and treatment of PROM. Functional prediction provided a direction for further research on the mechanism of PROM. The established prediction model could prevent the occurrence of PPROM and promote maternal and infant health.