A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) method was established for simultaneous determination of seven characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rat plasma, including galangin, kaempferol, kaempferide, pinocembrin, 1,7-diphenyl-4-en-3-heptanone, 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA), and 7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-4-en-3-heptanone(DPHB). The new developed HPLC-MS/MS method was applied to study the pharmacokinetics of the 7 characteristic components in rats with Helicobacter pylori gastritis. A Waters Sunfire C_(18) column(2.1 mm×150 mm, 3.5 μm) was used. The acetonitrile-aqueous solution(containing 0.1% formic acid) was adopted as the mobile phase for gradient elution. Seven components and internal standard(chlorogenic acid) were separated within 12 min. Mass spectrometric detection was performed in multiple reaction monitoring(MRM) mode using electrospray ionization(ESI) source with fast switching between positive and negative ions. The method was verified by specificity, linearity, precision, accuracy, recovery, matrix effect, and stability and met the requirements of pharmacokinetic study on the 7 components in rat plasma. Pharmacokinetic results showed that the average peak time(T_(max)) of the 7 components was 0.31-2.19 h, their elimination half-life(t_(1/2)) was 5.26-16.65 h, and the average residence time(MRT) was 6.29-31.03 h after the oral administration of the active fraction of Alpiniae Officinarum Rhizoma to rats with H. pylori gastritis. The plasma exposure levels of galangin and DHPA were higher than those of the other components. The concentration-time curves of four detected flavonoids showed obvious double peaks. This study elucidated the pharmacokinetic characteristics of 7 characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rats with H. pylori gastritis, providing a scientific basis for the identification of the pharmacodynamic substances of Alpiniae Officinarum Rhizoma for treatment of H. pylori gastritis and the clinical application of Alpiniae Officinarum Rhizoma in the prevention and treatment of H. pylori gastritis.
Animals ; Rats ; Chromatography, High Pressure Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Helicobacter pylori/drug effects* ; Alpinia/chemistry* ; Rats, Sprague-Dawley ; Gastritis/metabolism* ; Helicobacter Infections/metabolism* ; Flavonoids/blood* ; Rhizome/chemistry* ; Liquid Chromatography-Mass Spectrometry

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male ; Child ; Female ; Humans ; Child, Preschool ; Receptors, Tumor Necrosis Factor, Type I/genetics* ; Retrospective Studies ; Hereditary Autoinflammatory Diseases/drug therapy* ; Glucocorticoids/therapeutic use* ; Biological Factors/therapeutic use* ; Immunosuppressive Agents/therapeutic use* ; Autoantibodies ; Familial Mediterranean Fever/diagnosis* ; Mutation

Aim To explore whether isopropyl3-(3, 4-dihydroxyphenyl) -2-hydroxypropanoate (IDHP) could inhibit fat accumulation in liver cells by improving mitochondrial function, and alleviate the symptom of excessive fat accumulation in patients with NAFLD. Methods Cell steatosis model was established by inducing hepatocyte fat accumulation using palmitic acid and oleic acid (PA: OA molar ratio =1

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*

Humans ; Hemolysis ; Lymphoma, Large B-Cell, Diffuse/complications* ; Rituximab ; Pancreatic Neoplasms/complications*

Objective: To compare the efficacies between open surgery and axillary non-inflatable endoscopic surgery in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 343 patients with unilateral PTC treated by traditional open surgery (201 cases) and transaxillary non-inflating endoscopic surgery (142 cases) from May 2019 to December 2021 in the Head and Neck Surgery of Sichuan Cancer Hospital. Among them, 97 were males and 246 were females, aged 20-69 years. 1∶1 propensity score matching (PSM) was performed on the enrolled patients, and the basic characteristics, perioperative clinical outcomes, postoperative complications, postoperative quality of life (Thyroid Cancer-Specific Quality of Life), aesthetic satisfaction and other aspects of the two groups were compared after successful matching. SPSS 26.0 software was used for statistical analysis. Results: A total of 190 patients were enrolled after PSM, with 95 cases in open group and 95 cases in endoscopic group. Intraoperative blood losses for endoscopic and open groups were [20 (20) ml vs. 20 (10) ml, M (IQR), Z=-2.22], postoperative drainage volumes [170 (70)ml vs. 101 (55)ml, Z=-7.91], operative time [135 (35)min vs. 95 (35)min, Z=-7.34], hospitalization cost [(28 188.7±2 765.1)yuan vs. (25 643.5±2 610.7)yuan, x¯±s, t=0.73], postoperative hospitalization time [(3.1±0.9)days vs. (2.6±0.9)days, t=-3.24], and drainage tube placement time [(2.5±0.8) days vs. (2.0±1.0)days, t=-4.16], with statistically significant differrences (all P<0.05). There was no significant difference in surgical complications (P>0.05). There were significant diffferences between two groups in the postoperative quality of life scores in neuromuscular, psychological, scar and cold sensation (all P<0.05), while there were no statistically significant differences in other quality of life scores (all P>0.05). In terms of aesthetic satisfaction 6 months after surgery, the endoscopic group was better than the open group, with statistically significant difference (χ²=41.47, P<0.05). Conclusion: Endoscopic thyroidectomy by a gasless unilateral axillary approach is a safe and reliable surgical method, which has remarkable cosmetic effect and can improve the postoperative quality of life of patients compared with the traditional thyroidectomy.
Male ; Female ; Humans ; Thyroid Cancer, Papillary/surgery* ; Retrospective Studies ; Quality of Life ; Thyroid Neoplasms/pathology* ; Endoscopy ; Thyroidectomy/methods*

Circular RNAs (circRNAs),a kind of novel non-coding RNAs, have been shown to play animportant role in cellular redox reactions. In the previous study, we found that hsa_circ_0087354 wasclosely related to the cellular redox state by real-time PCR. After overexpression of hsa_circ_0087354, the relative expression of ROS1 were decreased significantly (P < 0. 01), while the levels of SOD1 wereincreased significantly (P < 0. 05) . The activities of SOD and Gpx as well as GSH concentration weresignificantly increased (P < 0. 01), and cell proliferation was promoted in cells (P < 0. 05) . Bioinformatics analysis predicted that there were binding sites between hsa-miR-199-3p and hsa_circ_0087354 as well as solute carrier family 7 member 11 (SLC7A11), which might have a targetedregulatory relationship. Dual luciferase reporter assay confirmed the targeted regulatory relationshipbetween hsa-miR-199-3p with hsa_circ_0087354, and SLC7A11. Overexpressed hsa_circ_0087354 plasmid and ctrl plasmid were constructed, hsa-miR-199a-3p, hsa-miR-199b-3p and hsa-miR-NC mimicswere synthesized. Real-time PCR analysis showed that the relative expression of hsa-miR-199-3p was observably decreased (P < 0.01), while the relative expression of SLC7A11 in cells was dramaticallyincreased after transfection of has_circ_0087354 plasmid (P < 0.05) . After transfection with hsa-miR-199-3p, the relative expressions of SLC7A11 were markedly decreased (P < 0.001) . The activities ofSOD and Gpx, GSH concentration (P<0.01), and cell proliferation rate (P < 0.05) were significantlyreduced. In conclusion, hsa_circ_0087354 could enhance the expression of SLC7A11, promote theproliferation of cells and reduce the oxidative stress by adsorption of hsa-miR-199-3p.

Chronic kidney disease (CKD) is a progressive disease with many complications (eg, cardiovascular disease and acidosis and anemia) and high morbidity and mortality occurs in the population. There is no cure for this disease, current treatments including renin-angiotensin-aldosterone pathway inhibitors and sodium-glucose co-transporter 2 inhibitors can only delay the progression to end-stage renal disease. With the identification of more key factors and mechanisms in CKD development, new potential therapeutic approaches for CKD can be developed. This review summarizes the mainstays of therapy and strategies for CKD and related comorbidities to support the development of novel treatments.

OBJECTIVE: To investigate the clinicopathologic features and prognostic factors in oral basaloid squamous cell carcinoma. METHODS: Retrospective analysis of oral basaloid squamous cell carcinomas patients who underwent tumor resection during the period from January 2002 to December 2020 in the authors' hospital, especially the clinicopathologic characteristics of 28 cases with confirmed diagnosis and follow-up data. Immunohistochemistry was performed to define the helpful markers for differentiation diagnosis. The factors influencing the prognosis were evaluated based on Kaplan-Meier method. RESULTS: The tongue and mouth floor (11 cases, 39.3%) were the most frequently involved sites, followed by gingiva (6 cases, 21.4%), buccal (5 cases, 17.9%), palate (4 cases, 14.3%), and oropharynx (2 cases, 7.1%). The majority of basaloid squamous cell carcinomas were in advanced stage, with 12 cases in stage Ⅱ and 16 cases in stages Ⅲ-Ⅳ. Twelve of 28 patients were identified to have cervical lymph node metastasis, which was confirmed by histopathological examination. The incidence rate of lymph node metastasis was 42.9% (12/28). Nine tumors recurred, with one metastasized to the lung. At the meantime, the 28 conventional squamous cell carcinomas were matched with the same stage, among which 13 cases were identified with cervical lymph node metastasis. The incidence rate of lymph node metastasis was 46.4% (13/28). Five cases recurred, with two cases that metastasized to the lung and one to the brain. The 5-year overall survival rates of the basaloid squamous cell carcinoma and conventional squamous cell carcinoma patients were 54.6% and 53.8%, respectively. Histopathologically, basaloid cells consisted of tumor islands without evident keratinization but frequently with comedo-like necrosis within the tumor islands. CK5/6 and P63 exhibited strongly positive in all the 28 cases, whereas neuroendocrine markers, CgA and Syn, were negative. Eight cases positively expressed P16; one case showed focal SOX10 positive but CK7 negative. CONCLUSION The majority of oral basaloid squamous cell carcinomas present in advanced stage with a high tendency to lymph node metastasis, but the overall survival rates are not significantly different from conventional squamous cell carcinomas matched with the same stage. The human papilloma virus (HPV), as HPV-positivity rate is high, correlates to good prognosis. In addition, CK7 & SOX10 immunohistochemistry could contribute to differential diagnosis for basaloid squamous cell carcinoma with solid adenoid cystic carcinoma.
Carcinoma, Adenoid Cystic ; Carcinoma, Squamous Cell ; Humans ; Immunohistochemistry ; Neoplasm Recurrence, Local/epidemiology* ; Retrospective Studies