[Objective]To elucidate the role and molecular mechanisms of Liuwei Dihuang Decoction(LWDHD)in the treatment of experimental autoimmune encephalomyelitis(EAE).[Methods]Sixty male C57BL/6 mice were randomly divided into normal group,model group,positive control group[prednisone acetate(PA)],LWDHD low-dose group(7.7 g·kg-1),medium-dose group(15.4 g·kg-1)and high-dose group(30.8 g·kg-1).Mice EAE model was established by using myelin oligodendrocyte glycoprotein 35-55(MOG 35-55)combined with pertussis toxin(PTX)and tuberculin.The mice in LWDHD groups were given LWDHD by gavage for 20 consecutive days,and the mice in positive control group were given PA of 6 mg·kg-1 by gavage.Neurological damage was evaluated by neurological functional impairment scores,hematoxylin-eosin(HE)staining was used to detect pathological changes in brain tissue,interleukin-1β(IL-1β)and interleukin-6(IL-6)levels were detected by enzyme-linked immunosorbent assay(ELISA),and Western blot was utilized to examine the expression of proteins in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)pathway.T lymphocytes were extracted from the spleen of mice and treated with LWDHD containing serum.Flow cytometry was used to evaluate the proportion of CD4+and CD8+T lymphocytes and Western blot was used to detect the effect of LWDHD on the expression of proteins in the TLR4/NF-κB pathway.[Results]Different concentrations of LWDHD significantly improved the neurological function scores in EAE mice(P<0.01),reduced the abnormal proliferation of microglia in the cerebral cortex,and decreased neuronal cell death in the hippocampus.ELISA showed that LWDHD significantly inhibited the secretion of IL-1β and IL-6(P<0.01).Western blot analysis indicated that LWDHD markedly suppressed the expression and activation of proteins in the TLR4/NF-κB pathway(P<0.01).In cellular experiments,LWDHD containing serum significantly reduced the proportion of CD4+and CD8+T lymphocytes,and inhibited the expression and activation of proteins in the TLR4/NF-κB pathway(P<0.01).[Conclusion]LWDHD significantly inhibits brain inflammatory responses in EAE mice and reduces abnormal proliferation of microglia,which may be associated with the inhibition of protein activation in brain tissue and T lymphocytes via the TLR4/NF-κB pathway.

The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals

Pulmonary alveolar proteinosis(PAP)is a rare progressive respiratory dysfunction disease of the lung characterized by insidious onset and non-specific clinical manifestations,often leading to misdiagnosed and mistreated.Herein,we reported a case of PAP patient admitted to Jiading District Central Hospital with an atypical appearance of alveolar lavage fluid and whose condition improved significantly after treatment with subcutaneous injection of recombinant human granulocyte-macrophage colony stimulating factor(GM-CSF).Additionally,we have reviewed and summarized the relevant literature to enhance the understanding of the diagnosis and treatment of this disease.

[Objective]To elucidate the role and molecular mechanisms of Liuwei Dihuang Decoction(LWDHD)in the treatment of experimental autoimmune encephalomyelitis(EAE).[Methods]Sixty male C57BL/6 mice were randomly divided into normal group,model group,positive control group[prednisone acetate(PA)],LWDHD low-dose group(7.7 g·kg-1),medium-dose group(15.4 g·kg-1)and high-dose group(30.8 g·kg-1).Mice EAE model was established by using myelin oligodendrocyte glycoprotein 35-55(MOG 35-55)combined with pertussis toxin(PTX)and tuberculin.The mice in LWDHD groups were given LWDHD by gavage for 20 consecutive days,and the mice in positive control group were given PA of 6 mg·kg-1 by gavage.Neurological damage was evaluated by neurological functional impairment scores,hematoxylin-eosin(HE)staining was used to detect pathological changes in brain tissue,interleukin-1β(IL-1β)and interleukin-6(IL-6)levels were detected by enzyme-linked immunosorbent assay(ELISA),and Western blot was utilized to examine the expression of proteins in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)pathway.T lymphocytes were extracted from the spleen of mice and treated with LWDHD containing serum.Flow cytometry was used to evaluate the proportion of CD4+and CD8+T lymphocytes and Western blot was used to detect the effect of LWDHD on the expression of proteins in the TLR4/NF-κB pathway.[Results]Different concentrations of LWDHD significantly improved the neurological function scores in EAE mice(P<0.01),reduced the abnormal proliferation of microglia in the cerebral cortex,and decreased neuronal cell death in the hippocampus.ELISA showed that LWDHD significantly inhibited the secretion of IL-1β and IL-6(P<0.01).Western blot analysis indicated that LWDHD markedly suppressed the expression and activation of proteins in the TLR4/NF-κB pathway(P<0.01).In cellular experiments,LWDHD containing serum significantly reduced the proportion of CD4+and CD8+T lymphocytes,and inhibited the expression and activation of proteins in the TLR4/NF-κB pathway(P<0.01).[Conclusion]LWDHD significantly inhibits brain inflammatory responses in EAE mice and reduces abnormal proliferation of microglia,which may be associated with the inhibition of protein activation in brain tissue and T lymphocytes via the TLR4/NF-κB pathway.

Pulmonary alveolar proteinosis(PAP)is a rare progressive respiratory dysfunction disease of the lung characterized by insidious onset and non-specific clinical manifestations,often leading to misdiagnosed and mistreated.Herein,we reported a case of PAP patient admitted to Jiading District Central Hospital with an atypical appearance of alveolar lavage fluid and whose condition improved significantly after treatment with subcutaneous injection of recombinant human granulocyte-macrophage colony stimulating factor(GM-CSF).Additionally,we have reviewed and summarized the relevant literature to enhance the understanding of the diagnosis and treatment of this disease.

Objective To investigate the clinical value of prophylactic high-flow nasal cannula oxygen therapy (HFNC) in reducing postoperative pulmonary complication (PPC) in elderly patients with non-small cell lung cancer (NSCLC). Methods The clinical data of elderly patients (over 60 years) with NSCLC who underwent video-assisted thoracoscopic lobectomy or segmental resection at the Department of Thoracic Surgery, Fujian Provincial Hospital from January 2021 to March 2022 were retrospectively analyzed. According to whether receiving HFNC after surgery, they were divided into a conventional oxygen therapy (CO) group and a HFNC group. The CO group were matched with the HFNC group by the propensity score matching method at a ratio of 1 : 1. We compared PPC incidence, white blood cell (WBC) count, procalcitonin and C-reactive protein on postoperative day (POD) 1, 3 and 5 and postoperative hospital stay between the two groups. Results A total of 343 patients (165 males, 178 females, average age of 67.25±4.79 years) were enrolled, with 53 (15.45%) receiving HFNC. Before matching, there were statistical differences in gender, rate of combined chronic obstructive pulmonary disease, pathology type and TNM stage between the two groups (all P<0.05). There were 42 patients successfully matched in each of the two groups, with no statistical difference in baseline characteristics (P>0.05). After propensity score matching, the results showed that the PPC incidence in the HFNC group was lower than that in the CO group (23.81% vs. 45.23%, P=0.039). WBC count on POD 3 and 5 and procalcitonin level on POD 3 were less or lower in the HFNC group than those in the CO group [ (8.92±2.91)×109/L vs. (10.62±2.67)×109/L; (7.68±1.58)×109/L vs. (8.86±1.76)×109/L; 0.26 (0.25, 0.44) μg/L vs. 0.31 (0.25, 0.86) μg/L; all P<0.05]. There was no statistical difference in the other inflammatory indexes or the postoperative hospital stay between the two groups (P>0.05). Conclusion Prophylactic HFNC can reduce the PPC incidence and postoperative inflammatory indexes in elderly patients with NSCLC, but does not shorten the postoperative hospital stay.

Objective:To investigate the efficacy and safety of kidney sparing treatment based on Thulium laser ablation and systematic therapy in localized high-risk upper urinary tract urothelial carcinoma (UTUC).Methods:The data of 10 patients with UTUC who received combined treatment based on Thulium laser and systematic treatment from January 2020 to December 2021 in West China Hospital were retrospectively analysed. There were 5 males and 5 females with a median age of 76 (range 52 to 87)years old. Three cases were renal pelvis tumor and 7 cases were ureter tumor including 5 cases in lower ureter and 2 cases in upper and middle ureter. Five cases were with positive urine cytology and 6 cases were with hydronephrosis. One case was muscular invasion UTUC confirmed by biopsy(cT 2+), 7 cases were high-grade invasive urothelial carcinoma (cT 1+), and 2 cases were high-grade papillary urothelial carcinoma (cT a). Among 10 cases, 5 patients refused radical nephroureterectomy(RUN), among whom 3 patients were too old or in poor general condition to tolerate RNU. One case had a solitary kidney and 1 case had bilateral tumours. Patients were treated with Thulium laser tumor ablation under ureteroscopy combined with systemic therapy. The perioperative systemic treatment included platinum-based chemotherapy±immunotherapy, RC48+ immunotherapy, and immunotherapy alone. The postoperative treatment was immunotherapy maintenance±local radiotherapy. Strict follow-up was conducted after the completion of treatment. Results:Nine patients received systemic therapy before ablation. Four cycles of platinum-based chemotherapy (cisplatin in 2 cases, carboplatin in 1 case) were used in 3 cases, and platinum-based chemotherapy + immunotherapy (6 cycles of cisplatin + toripalimab in 1 case, 4 cycles of cisplatin + toripalimab in 1 case, 4 cycles of carboplatin+ trelizumab in 1 case) was used in 3 cases, four cycle of RC48 + immunotherapy (toripalimab or trelizumab) were used in 2 cases, and four cycles of immunotherapy (toripalimab) were used in 1 case. The operations of 10 cases were successfully completed without serious complications during the perioperative period and the laser working time (42.4 ± 15.2) min. Of the 10 cases, 4 achieved complete ablation at the first ablation, and 6 patients had incomplete ablation. Among them, 2 patients achieved clinical complete remission after 1-2 cycles of systemic therapy, and 4 patients achieved complete ablation after Thulium laser ablation again.All the 10 patients were treated with immunotherapy for 1 year, and 2 of them received additional adjuvant radiotherapy. The patients were followed-up for median 40 months(range 26 to 53 months). Recurrence occurred in 5 cases, of which 3 cases underwent salvage nephroureterectomy and 2 cases underwent Thulium laser ablation under ureteroscopy again. Five patients had no tumor recurrence. None of the 10 patients had distant metastasis. At the last follow-up, 1 patient died of complications and 6 patients kept the affected kidney alive. Perioperative complications including macroscopic hematuria (8 cases), fever (3 cases), the long-term complications of ureter stenosis (4 cases).Conclusions:For localized high-risk UTUC, local Thulium laser ablation combined with systemic therapy can achieve good tumor control while preserving the affected kidney in selected patients, and its potential application value should be further evaluated.

Objective:To explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) combined with blood glucose at admission for a positive blood culture for sepsis.Methods:A single-center retrospective cohort study was conducted. According to the 2016 American Society of Critical Care/European Society of Critical Care Medicine (SCCM/ESICM) and diagnostic criteria for sepsis and septic shock-3.0 (sepsis-3.0), patients with sepsis were admitted to the Emergency Department of Fujian Medical University Union Hospital for more than 24 h from January 2019 to December 2021 were enrolled. Age, gender, sequential organ failure assessment, source of infection, NLR, and blood culture results were recorded. Based on the blood culture results, patients were divided into a blood culture positive group (Gram-positive group, Gram-negative group) and blood culture negative group, and the differences between the groups were compared. The risk factors for a positive blood culture were analyzed using multivariate logistic regression. A receiver operating characteristic analysis was performed for the NLR combined with the blood glucose measurement.Results:A total of 265 patients with sepsis were included, of which 62 were positive in blood culture (15 Gram-positive patients, 37 Gram-negative patients and 10 fungal patients). The positive rate of blood culture was 23.4%. The number of patients with history of diabetes, neutrophil count, procalcitonin, blood glucose, and NLR in the positive blood culture group were significantly higher than those in the negative blood culture group (all P<0.001). Multivariate logistic regression analysis revealed that random admission blood glucose ( OR=1.116, 95% CI: 1.051~1.186, P<0.001) and NLR ( OR=1.039, 95% CI: 1.015~1.064, P=0.001) were independent risk factors for blood culture positivity in sepsis patients. For patients with blood culture positive, and with Gram-negative bacterial bloodstream infections, the AUC of the NLR combined with the admission blood glucose level was 0.819 (95% CI: 0.761-0.877, P<0.001) and 0.871 (95% CI: 0.813-0.928, P<0.001), respectively. Conclusions:The combination of NLR and random admission blood glucose could provide a good predictive value for blood culture positive and gram-negative bacterial bloodstream infections in sepsis patients.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Aim To investigate the effect of terpinen-4-ol (T40) on inflammatory injury of vascular smooth muscle cells (VSMCs) induced by high glucose based on the improvement of autophagic flow disorder and involved molecular signals. Methods The scratch test was used to analyze the migration ability of VSMCs, the levels of IL-1β and IL-6 in cell culture supernatant were measured by ELISA, the expression levels of inflammation-related proteins NF-κb p65, p-NF-κb p65, IL-1β, IL-18 and autophagy-related proteins p62, LC3-HYLC3-I, Beclinl, p-Beclinl were de-tected by Western blot. Results T40 inhibited migration of VSMCs induced by high glucose, reduced the secretion and release of pro-inflammatory factors IL-1β and IL-6, inhibited the expression of p-NF-κb p65/ NF-κb p65, IL-1β, IL-18, downregulated the expression of p62, LC3-TJ/LC3- I and p-Beclinl at same time. After interfering the autophagic flux of VSMCs with autophagy inhibitor chloroquine (CQ) , T40 pre-treatment significantly inhibited the protein expression levels of the above inflammatory factors and autophagy-related signals which mediated by CQ. Conclusion T40 inhibits the inflammatory injury of VSMCs induced by high glucose through improving the autophagic flow disorder.