OBJECTIVE: To investigate the hepatotoxicity of alkaloids from Euodiae Fructus combined with berberine (BBR) in Zuojin Pill, and to preliminarily explore the possible detoxification mechanism of the combination components. METHODS: The combination ratio of components was determined by the maximum concentration (Cmax) of the chemical components in Zuojin Pill. HepG2 cell model was used to investigate the combined toxicity of the hepatotoxic components from Euodiae Fructus, such as evodiamine (EVO) or dehydroevodiamine (DHED), with BBR for 48 h. The experimental groups were set as follows: the vehicle control group, the EVO group, the DHED group, the BBR group, and the combination group of EVO or DHED with BBR. The cell counting kit-8 (CCK-8) method was used to determine the cell viability, and the combination index (CI) was used to determine the combined toxicity of the components. The alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydroge-nase (LDH), and alkaline phosphatase (ALP) activities as well as total bilirubin (TBIL) content in the cell culture supernatant were detected. The protein expression levels of bile acid transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2), were detected by Western blot. The intracellular malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in HepG2 cells were detected. RESULTS: Compared with EVO or DHED group, the combination of EVO 1 μmol/L with BBR 10 μmol/L or DHED 50 μmol/L with BBR 35 μmol/L significantly increased cell viability of HepG2 cells (P < 0.01), with CI values of 77.89 or 4.49, respectively, much greater than 1. Significant decreases in the activities of ALT, AST, LDH, ALP, and TBIL content in the cell culture supernatant were found in both combination groups (P < 0.05, P < 0.01). Compared with the EVO group, the combination of EVO with BBR upregulated the protein expression levels of BSEP and MRP2. Compared with the DHED group, the combination of DHED with BBR significantly downregulated the protein expression levels of BSEP and MRP2 (P < 0.01). Compared with EVO or DHED group, the combination of EVO or DHED with BBR significantly reduced the MDA content in HepG2 cells (P < 0.05, P < 0.01). CONCLUSION A certain ratio of BBR combined with EVO or DHED had an antagonistic effect on HepG2 cytotoxicity, which might be related to regulating the expression of bile acid transpor-ters, and reducing lipid peroxidation damage.
Humans ; Hep G2 Cells ; Berberine/pharmacology* ; Drugs, Chinese Herbal/toxicity* ; Evodia/chemistry* ; Alkaloids/pharmacology* ; Cell Survival/drug effects* ; Multidrug Resistance-Associated Proteins/metabolism* ; Multidrug Resistance-Associated Protein 2 ; Quinazolines

Objective To classify traumatic triangular fibrocartilage complex(TFCC)injury based on 3.0T MR.Methods A total of 46 patients with definite history of wrist trauma admitted were collected.All patients underwent MRI scanning within 3 days after trauma,and the MRI findings were classified as follows according to the Palmer classification criteria:the focal structures of triangular fibro-cartilage(articular disc)(TFC)injury,the horizontal of the articular disc tear,injuries of ulnar styloid attachment and ulnar fovea attach-ment in TFC,ulnolunate and ulnotriquetral ligaments injuries,injury of the radial sigmoid notch junction,meniscal homologous inju-ry.The presence of TFCC injury was eventually confirmed by surgery in all patients.Results Of 46 patients,38 patients could be classified by Palmer,and there were 10 cases with type ⅠA,23 cases with type ⅠB,3 cases with type ⅠC and 2 cases with type ⅠD.A total of 8 patients were not suitable for Palmer type,and there were 3 patients with horizontal tears in the articular disc and 5 patients with meniscus homologous injuries.Conclusion The 3.0T MR can not only show various subtypes of Palmer classification,but also refine and supplement the classification based on the original classification,such as the injuries of ulnar styloid attachment and ulnar fovea attachment at the ulnar end of the articular disc,horizontal tear of the articular disc,meniscus homologous injury,etc.

Objective:To evaluate the effect of the right stellate ganglion block (SGB) on the acute lung injury induced by hind limb ischemia-reperfusion (I/R) in rats.Methods:Twenty-seven SPF healthy male Sprague-Dawley rats, aged 7-8 weeks, weighing 200-250 g, were divided into 3 groups ( n=9 each) by the random number table method: sham operation group (Sham group), hind limb I/R group (I/R group) and right SGB+ hind limb I/R group (SGB+ I/R group). The right hind limb I/R injury model was developed in anesthetized rats in I/R and SGB+ I/R groups, and the right SGB was performed with 0.2% ropivacaine 0.5 ml before the right hind limb ischemia in SGB+ I/R group. The pathological changes of lung tissues were observed with a light microscope, the wet/dry lung weight ratio, PaO 2 and PaCO 2 were determined, and the oxygenation index was calculated. The concentrations of serum malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were determined using enzyme-linked immunosorbent assay. Results:Compared with Sham group, the wet/dry lung weight ratio, PaO 2, oxygenation index, and GSH-Px concentrations were significantly decreased, and the concentrations of serum MDA were increased in I/R and SGB+ I/R groups ( P<0.05). Compared with I/R group, the wet/dry lung weight ratio, PaO 2, oxygenation index, and GSH-Px concentrations were significantly increased, the concentrations of serum MDA were decreased ( P<0.05), and the pathological changes of lung tissues were significantly attenuated in SGB+ I/R group. There was no significant difference in PaCO 2 among the 3 groups ( P>0.05). Conclusions:The right SGB can alleviate the acute lung injury induced by hind limb I/R, and the mechanism may be related to the inhibition of oxidative stress responses in rats.

Objective:To analyze the etiological characteristics of epidemic cerebrospinal meningitis caused by serogroup Y Neisseria meningitidis ( Nm) in Fujian Province. Methods:The strain identification, serogroup identification, antimicrobial susceptibility test, molecular typing, average nucleotide identity (ANI), core genome multilocus sequence typing (cgMLST), and single nucleotide polymorphism (SNP) analysis were performed on eight Nm strains isolated from cases of epidemic cerebrospinal meningitis, close contacts, or healthy population. Results:All eight isolates from Fujian Province in 2024 were serogroup Y Nm strains. The antimicrobial susceptibility test for 12 antibiotics showed that all isolates from Fujian Province in 2024 were resistant to trimethoprim-sulfamethoxazole, and NMFJ202406 and NMFJ202407 isolates were resistant to nalidixic acid and intermediate to ciprofloxacin, while the others were sensitive to antibiotics such as penicillin, cefotaxime, and ceftriaxone. All isolates were ST-1655 sequence type (ST), except for NMFJ202406 isolate which were ST-2039, and all isolates belonged to clonal complex 23 (CC23). The finetyping antigen profile of all isolates were P1.5-1, 10-1: F4-1. ANI and phylogenetic analysis indicated that the isolates in Fujian Province were mainly divided into two clusters, namely NMFJ202401 and its close contact isolates (NMFJ202402-NMFJ202405), as well as NMFJ202406, NMFJ202407, and NMFJ202408 isolates. Compared to the isolates from Guangdong, Shanghai, and Hebei Provinces, the strains isolated in Fujian Province were more closely related to the strains isolated in Canada (NML2019-167, 2019), Japan (NIID501, 2009), and the United Kingdom (CA41956, 2015), respectively. Conclusions:This is the first report of epidemic cerebrospinal meningitis caused by serogroup Y Nm isolates in Fujian Province, which might be transmitted from different sources abroad and have spread in many areas. In the future, the wider usage of tetravalent meningococcal vaccine ACYW135 is needed, and the epidemiological and etiological surveillance of serogroup Y epidemic cerebrospinal meningitis should be strengthened.

Objective:To investigate the safety, feasibility and accuracy of esophageal sponge cytology in esophageal carcinoma screening in high-incidence districts.Methods:Opportunistic screening for esophageal carcinoma was conducted on individuals aged 40-75 years with high-risk factors for esophageal carcinoma and visited out-patient clinic in Lianshui People's Hospital from May 2021 to June 2022. A new esophageal cell collector independently developed in China was used for esophageal sponge cytology sampling followed by cytopathological analysis. Atypical squamous cells or more severe lesions were defined as positive esophageal sponge cytology. Then gastroscopy was performed, and all suspicious areas under the endoscopy were biopsied for histopathological examination. Gastroscopy, biopsy histopathology and esophageal sponge cytology were conducted blindly in pairs. Outcome measures included adverse reactions during sampling, subject tolerability (using a visual simulation score), sampling quality, and diagnostic efficacy of esophageal sponge cytology using gastroscopy plus biopsy histopathology as the gold standard.Results:A total of 1 590 patients completed the screening program. During esophageal sponge cytology sampling, no serious adverse events were observed, and the adverse reactions were mainly manifested as vomiting during sampling [0.31% (5/1 590)] and sore throat after sampling [2.45% (39/1 590)], all of which resolved spontaneously without further medical intervention. The majority of subjects [98.62% (1 568/1 590)] reported good tolerance during the procedure. After sampling, 1 526 (95.97%) subjects had completely expanded sponge material, meeting the standard of good sampling quality. The scanning analysis of the digital pathology system showed that the number of sampled cells in 1 590 subjects ranged (2.01-4.00)×10 6, with a median of 3.48×10 6 cells, which could meet the requirements for interpreting cytological results. Using the positive esophageal sponge cytology for the diagnosis of esophageal carcinoma including high-grade intraepithelial neoplasia, esophageal squamous cell carcinoma and adenocarcinoma of esophagogastric junction, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 98.57% (69/70), 91.51% (1 391/1 520), 34.85% (69/198), 99.93% (1 391/1 392), and 91.82% (1 460/1 590), respectively. Conclusion:Esophageal sponge cytology presents promising diagnostic efficacy for esophageal carcinoma screening, offering a simple, safe, convenient, and effective approach in high-incidence esophageal carcinoma regions.

Allergic rhinitis（AR） is an independent risk factor for allergic asthma. Some AR patients may have developed airway hyperresponsiveness（AHR） in the absence of asthma symptoms. In this stage, AHR is often neglected due to the absence of typical asthma symptoms. Exploring the clinically relevant risk factors for AHR in patients with AR, as well as the clinical indicators and biomarkers to predict AHR in patients with AR, is of great significance to the prevention of the occurrence of AHR and asthma. This review summarized the risk factors for the development of AHR in AR patients, and gave hints to the prevention of AHR in AR patients.
Humans ; Rhinitis, Allergic ; Respiratory Hypersensitivity ; Asthma ; Risk Factors

Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.
Asthma ; Humans ; Inflammation ; Respiratory System ; Rhinitis, Allergic ; Sinusitis

Objective:To investigate the implementation status of sepsis hour-1 bundle strategy for patients with septic shock in emergency department.Methods:A total of 116 septic shock patients admitted to the emergency department from January 2020 to December 2020 were included in this prospective study, and the implementation of sepsis bundles and the clinical outcomes of patients were recorded.Results:Among 116 patients, 20 cases (17.2%) had lactic acid monitored within 1 h, 20 cases (17.2%) had blood culture before antibiotics, 82 cases (70.1%) received broad-spectrum antibiotics, 16 cases (13.8%) received fluid resuscitation ≥30 ml/kg, and 57 cases (49.1%) received vasoactive drugs during resuscitation. Finally, the sepsis hour-1 bundle strategy was fully implemented only in 13 cases (11.2%). Compared with the group with incomplete implementation of sepsis hour-1 bundle strategy, the volume of fluid recovery in the group with full implementation was significantly increased [33.7 (30.0,37.5) vs. 8.9(7.3,10.8) ml/kg, Z=-4.78, P<0.001], mean artery blood pressure significantly increased [70.0 (70.0,76.7) vs. 67.7 (61.7,76.7)mmHg(1 mmHg=0.133 kPa) , Z=-2.00, P<0.001], and lactic acid significantly decreased [3.0 (2.0,3.2) vs. 4.4 (3.7,7.2) mmol/L, Z=-2.76, P=0.006]. However, there were no significant differences in ICU mortality, in-hospital mortality and 28-day mortality between the two groups ( P>0.05). Conclusions:Septic shock patients in emergency department have poor compliance with the implementation of sepsis hour-1 bundle strategy, and relevant management training should be strengthened.

Objective:To investigate the efficacy of bare stent implantation alone and stent assisted coiling in the repair of isolated superior mesenteric artery dissection (ISMAD) false lumen.Methods:Clinical data of 50 patients with ISMAD who underwent endovascular treatment between December 2012 and March 2021 were analyzed retrospectively. Depending on the endoluminal treatment methods, they were divided into the bare stent implantation alone group (29 cases) and the stent assisted coiling group (21 cases), and the rates of complete postoperative dissection remodeling, stent restenosis, and symptom recurrence were compared between the two groups.Results:The rates of complete remodeling of the dissection in the immediate postoperative period, 3 months and 6 months in the bare stent placement alone group were 13.8% (4/29), 51.7% (15/29) and 75.9% (22/29), respectively, which were lower than that of the stent assisted coiling group 71.4% (15/21), 85.7% (18/21), and 100% (21/21), and the difference was statistically significant (χ 2=17.17, 6.27, 4.06 respectively, and P=0.001, 0.012, 0.044 respectively). While the rates of complete remodeling of the dissection were 82.8%(24/29), 100%(21/21) in the two groups at 12 months after surgery, respectively, and the difference was not statistically significant (χ 2=2.34, P=0.126). There was no significant difference in stent patency rate and symptom recurrence rate between the two groups ( P>0.05). Conclusions:The efficacy of bare stent implantation alone and stent assisted coiling in the treatment of ISMAD is definite. Although the rate of complete remodeling of the dissection with bare stent placement alone is low in the short term, the rate of complete remodeling of the dissection with bare stent implantation alone gradually increases with the extension of time, which is worthy of clinical application and promotion.

With the enormous resources having been invested in oncology drugs development in China in recent years, the Center for Drug Evaluation (CDE) of National Medical Products Administration has been issuing a number of technical guidelines to further standardize the requirements on implementation and registration of domestic oncology clinical trials. As data is the cornerstone of clinical trials, data integrity and quality will directly decide the outcome of clinical studies. Given the specific characteristics of oncology therapeutic clinical trials, and combined with the clinical data standards established by the Clinical Data Interchange Standards Consortium (CDISC) and the issued industrial guidelines, this article introduces the general considerations of clinical data management for oncology clinical trials, with the aim of emphasizing normative data collection and timely data monitoring to ensure the data quality and reliability of results of the study. This article discusses the impact of complex study design on CRF, design CRF according to CDASH, develop DVP scientifically, rolling submissions and data cut-off.