OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

As an innovative dosage form, traditional Chinese medicine(TCM) dry powder inhalers have emerged as a focal point in the research and development of new preparations due to its high efficiency, safety, and bioavailability. This paper systematically reviewed the relevant literature and patents associated with TCM dry powder inhalers to analyze the origins and the current research and development status. Furthermore, this paper probed into the research and development ideas of TCM dry powder inhalers regarding clinical positioning, prescription screening, and druggability. Additionally, the paper thoroughly analyzed the technical barriers in druggability studies and elaborated on corresponding research techniques and coping measures. Furthermore, it emphasized the need for improved regulations and policies governing TCM dry powder inhalers, advocated for strengthened oversight, and called for the establishment of a scientific quality evaluation system. Measures such as promoting production-education-research collaboration, enhancing personnel training, and fostering international exchanges were proposed to provide a scientific and systematic reference for the future research, development, and application of TCM dry powder inhalers, thereby facilitating the rapid modernization of TCM.
Humans ; Dry Powder Inhalers/trends* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/instrumentation* ; Administration, Inhalation

Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.

Objective:To explore the predictive value of blood flow velocity changes in superior mesenteric artery (SMA) monitored by ultrasound on feeding intolerance (FI) of enteral nutrition (EN) in mechanically ventilated ICU patients. Methods:One-hundred and eight mechanically ventilated patients in Intensive Care Department of the Second People's Hospital of Nantong from February 2022 to February 2023 were enrolled. SMA blood flow parameters and enteral nutrition tolerance were monitored on the 1st,3rd,and 7th day (D1,D3,D7) after initiation of EN. Differences in SMA blood flow parameters between tolerant and intolerant group,as well as intolerant subgroups (mild,moderate,and severe) were analyzed. The predictive value of SMA blood flow parameters for FI and the risk factors of FI were also evaluated,and the relationship between SMA blood flow parameters and intestinal barrier function were preliminarily explored . Result:The SMA blood flow velocity parameters,peak systolic velocity (PSV) and end diastolic velocity (EDV),were higher at D1,D3,and D7 in the tolerant groups compared to the intolerant group (all P<0.05). Subgroup analysis showed that as the degree of intolerance increased,PSV gradually decreased. EDV at D1,D3,and D7 also gradually decreased with the increased severity of FI (all P<0.05);The AUC of PSV and EDV predicting FI in D1,D3,and D7 patients were 0.752 (95％ CI:0.660～0.830) and 0.773 (95％ CI:0.682～0.848),0.774 (95％ CI:0.683～0.849) and 0.796 (95％ CI:0.708～0.868),0.743 (95％ CI:0.650～0.822) and 0.713 (95％ CI:0.618～0.796). respectively. PSV,norepinephrine use,and blood phosphorus levels were independent prognostic factors for FI at D3. Patients with FI showed a negative correlation between PSV,EDV,and diamine oxidase (PSV:r=-0.857,P<0.001;EDV:r=-0.795,P<0.001). Conclusion:Changes in blood flow velocity in the superior mesenteric artery by ultrasound monitoring can effectively predict enteral nutrition intolerance in mechanically ventilated patients,it might have potential clinical application values in ICU patients.

AIM To study the chemical constituents from n-butanol fraction of Corydalis impatiens(Pall.)Fisch.and their antioxidant activities.METHODS The n-butanol fraction was isolated and purified by silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activities were determined by DPPH method and tyrosinase method.RESULTS Fourteen compounds were isolated and identified as nicotinamide(1),methyl L-pyroglutamate(2),bungeanoline F(3),monomethyl fumarate(4),5-hydroxymethylfurfural(5),4-hydroxybenzoic acid(6),hydroxybenzoate(7),methyl 3,4-dihydroxybenzoate(8),methyl ferulate(9),dimethylcaffeic acid(10),dimethyl feruloyl malate(11),(-)-4-O-feruloylquinic acid(12),syringaresinol(13)and(-)-loliolide(14).Compounds 1,8,11 and 13 showed strong antioxidant activites on DPPH free radicals,with IC50 values ranging from 54.47 to 97.4 μmol/L.Compound 13 had potential inhibitory effect on tyrosinase.CONCLUSION Compounds 4-14 are first isolated from Corydalis genus,and 3 is isolated from this plant for the first time.Compounds 1,8,11 and 13 have strong antioxidant activities.

Objective To investigate the effect of evodiamine on renal fibrosis in rats with chronic renal failure(CRF)by regulating sphingosine kinase 1(SphK1)/S1P signaling pathway.Methods CRF rat model was established by feeding 0.5％adenine diet.The rats after modeling were randomly divided into model group,evodiamine low-and high-dose groups,Niaoduqing Granules group and evodiamine high-dose+K6PC-5(SphK1 activator)group.At the end of intervention,the levels of 24-hour urinary protein(24 h-UTP),serum urea nitrogen(BUN)and serum creatinine(SCr)were detected.The levels of monocyte chemoattractant protein 1(MCP-1)and interleukin 6(IL-6)in serum of rats were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of renal tissue and collagen volume fraction(CVF)were observed by hematoxylin-eosin(HE)and Masson staining.The mRNA expressions of transforming growth factor β1(TGF-β1)and type Ⅳcollagen(COL-Ⅳ)in renal tissue were detected by real-time quantitative polymerase chain reaction(qRT-PCR).The protein expressions of SphK1 and S1P in renal tissue were detected by Western Blot.Results Compared with the normal group,the model group showed obvious inflammatory infiltration and collagen fiber deposition,the number of glomeruli decreased in renal tissue,and the expression levels of SCr,BUN,24h-UTP,IL-6,MCP-1,CVF,mRNA expressions of TGF-β1 and COL-Ⅳ,protein expessions of SphK1 and S1P were significantly increased(P＜0.05).Compared with the model group,the histopathological changes of the low-dose and high-dose evodiamine groups and the Niaoduqing Granules group was improved,and the expression levels of SCr,BUN,24 h-UTP,IL-6,MCP-1,CVF,mRNA expressions of TGF-β1 and COL-Ⅳ,protein expessions of SphK1 and S1P were significantly decreased.For intergroup comparison of each index,there were differences between the low-dose evodiamine group and the high-dose evodiamine group(P＜0.05),but there was no significant difference between the high-dose evodiamine group and the Niaoduqing Granules group(P＞0.05).Compared with the high-dose evodiamine group,the histopathological changes of the high-dose evodiamine+K6PC-5 group was further aggravated,and the improvement effect of all indexes were reversed(P＜0.05).Conclusion Evodiamine improves renal fibrosis in CRF rats by inhibiting SphK1/S1P signaling pathway.

Background/Aims: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. Methods: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. Results: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. Conclusions JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.

This study aims to investigate the effects of Blaps rynchopetera Fairmaire and/or cyclophosphamide on the proliferation and apoptosis of lung cancer cells and decipher the underlying mechanism. B. rynchopetera and cyclophosphamide-containing serum and blank serum were prepared from SD rats. Cell counting kit-8(CCK-8) assay was employed to examine the proliferation of lung cancer cell lines A549 and Lewis treated with corresponding agents. The Jin's formula method was used to evaluate the combined effect of the two drugs. According to the evaluation results, appropriate drug concentrations and lung cancer cell line were selected for subsequent experiments, which included control, B. rynchopetera, cyclophosphamide, B. rynchopetera + cyclophosphamide, and B. rynchopetera + Wnt/β-catenin pathway agonist lithium chloride(LiCl) groups. Immunocytochemistry was employed to measure the expression of proliferation-related proteins in Lewis cells after drug interventions. Flow cytometry was employed to determine the cell cycle and apoptosis. The expression levels of proliferating cell nuclear antigen(PCNA), cyclinD1, B-cell lymphoma 2(Bcl-2), Bcl-2-assiocated X protein(Bax), Wnt1, and β-catenin were determined by Western blot. The results showed that B. rynchopetera and/or cyclophosphamide significantly inhibited the proliferation of A549 and Lewis cells. Compared with B. rynchopetera alone, the combination increased the inhibition rate on cell proliferation. The combination of B. rynchopetera and cyclophosphamide demonstrated a synergistic effect according to Jin's formula-based evaluation. Compared with the control group, the B. rynchopetera, cyclophosphamide, and B. rynchopetera + cyclophosphamide groups showed increased proportion of Lewis cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the cyclophosphamide group, the combination group showed increased proportion of cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the B. rynchopetera group, the B. rynchopetera + LiCl group had deceased proportion of cells in G_0/G_1 phase, decreased apoptosis rate, down-regulated expression of Bax, and up-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. The results indicated that B. rynchopetera could inhibit the proliferation, arrest the cell cycle, and induce the apoptosis of lung cancer cells by inhibiting the Wnt/β-catenin signaling pathway. Moreover, B. rynchopetera had a synergistic effect with cyclophosphamide.
Rats ; Animals ; Wnt Signaling Pathway ; Lung Neoplasms/genetics* ; beta Catenin/metabolism* ; Proliferating Cell Nuclear Antigen ; bcl-2-Associated X Protein/metabolism* ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Proliferation ; Cyclophosphamide ; Cell Line, Tumor

Objective: To analyze the direct economic burden caused by measles cases in Shanghai from 2017 to 2019 and its influencing factors. Methods: A total of 161 laboratory-confirmed measles cases reported from January 1, 2017, to December 31, 2019, in Shanghai were included in the study through the "Measles Surveillance Information Reporting and Management System" of the "China Disease Surveillance Information Reporting and Management System". Through telephone follow-up and consulting hospital data, the basic information of population, medical treatment situation, medical treatment costs and other information were collected, and the direct economic burden of cases was calculated, including registration fees, examination fees, hospitalization fees, medical fees and other disease treatment expenses, as well as transportation and other expenses of cases. The multiple linear regression model was used to analyze the main influencing factors of the direct economic burden. Results: The age of 161 measles cases M (Q₁, Q₃) was 28.21 (13.33, 37.00) years. Male cases (56.52%) were more than female cases (43.48%). The largest number of cases was≥18 years old (70.81%). The total direct economic burden of 161 measles cases was 540 851.14 yuan, and the per capita direct economic burden was 3 359.32 yuan. The direct economic burden M (Q₁, Q₃) was 873.00 (245.01, 4 014.79) yuan per person. The results of multiple linear regression model analysis showed that compared with other and unknown occupations, central areas and non-hospitalized cases, the direct economic burden of measles cases was higher in scattered children, childcare children, students, and cadre staff in the occupational distribution, suburban areas and hospitalized, with the coefficient of β (95%CI) values of 0.388 (0.150-0.627), 0.297 (0.025-0.569), 0.327 (0.148-0.506) and 1.031 (0.853-1.209), respectively (all P values<0.05). Conclusion: The direct economic burden of some measles cases in Shanghai is relatively high. Occupation, area of residence and hospitalization are the main factors influencing the direct economic burden of measles cases.
Child ; Humans ; Male ; Female ; Adolescent ; Financial Stress ; Cost of Illness ; China/epidemiology* ; Health Care Costs ; Measles/epidemiology*