Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos (n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

Objective:To detect the expression of angiogenic factor (AGGF1) with G-patch and FHA domain 1 in hepatocellular carcinoma (HCC), and to investigate its relationship with HCC angiogenesis, invasion and metastasis and its clinical significance.Methods:A total of 90 primary HCC patients were selected from the Huangshi Central Hospital and Hubei Province Cancer Hospital from January 2019 to September 2020. Clinicopathological data of all patients were collected. The expression of AGGF1 and CD34 in cancer tissues of 90 HCC patients was detected by immunohistochemistry, and microvascular density (MVD) was calculated. The patients were followed up for three years. The relationship between AGGF1 and serum angiopoietin-2 (Ang-2) content, MVD, clinicopathological parameters and postoperative prognosis was analyzed.Results:The positive rate, relative expression level and MVD value of AGGF1 in HCC tissues were significantly higher than those in adjacent tissues (all P<0.05). The relative expression of AGGF1 in cancer tissues was positively correlated with the MVD value ( r=0.716). Serum Ang-2 content and MVD in AGGF1-positive patients were significantly higher than those in AgGF1-negative patients (all P<0.01). AGGF1 expression in HCC tissues was significantly correlated with tumor differentiation, tumor size, (China Liver Cancer (CNLC) staging, lymph node metastasis, vascular invasion, and postoperative recurrence and metastasis (all P<0.01). Kaplan-Meier analysis showed that the 2- and 3-year survival rates of patients with high AGGF1 expression were significantly lower than those of patients with low AGGF1 expression (all P<0.01). Multivariate analysis showed that CNLC stage, lymph node metastasis, vascular invasion, AGGF1 expression, postoperative recurrence and metastasis were the influencing factors for postoperative survival of HCC patients (all P<0.05). Conclusions:The high expression of AGGF1 can promote the angiogenesis of HCC, and is significantly correlated with invasion and metastasis and poor prognosis, which can be a potential evaluation indicator of HCC clinical prognosis.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To explore the postmortem diffusion rule of Aconitum alkaloids and their metabo-lites in poisoned rabbits,and to provide a reference for identifying the antemortem poisoning or post-mortem poisoning of Aconitum alkaloids.Methods Twenty-four rabbits were sacrificed by tracheal clamps.After 1 hour,the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration.Then,they were placed supine and stored at 25℃.The biological samples from 3 randomly selected rabbits were collected including heart blood,peripheral blood,urine,heart,liver,spleen,lung and kidney tissues at 0 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h after intragastric administration,respectively.Aconitum alkaloids and their metabolites in the biological samples were ana-lyzed by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Results At 4 h after intragastric administration,Aconitum alkaloids and their metabolites could be detected in heart blood,peripheral blood and major organs,and the contents of them changed dynamically with the preservation time.The contents of Aconitum alkaloids and their metabolites were higher in the spleen,liver and lung,especially in the spleen which was closer to the stomach.The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration.In contrast,the contents of Aconitum alkaloids and their metabolites in kidney were all lower.Aconi-tum alkaloids and their metabolites were not detected in urine.Conclusion Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits,diffusing from high-content organs(stomach)to other major organs and tissues as well as the heart blood.The main mechanism is the dispersion along the concentration gradient,while urine is not affected by postmortem diffusion,which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

OBJECTIVE To mine the adverse drug reaction （ADR） signals of melphalan， so as to provide reference for clinically safe drug use. METHODS Using OpenVigil 2.1 data platform， relative ADR reports of melphalan from the first quarter of 2004 to the second quarter of 2022 in FAERS database were collected； data mining was conducted using the reported odds ratio （ROR） method and Medicines and Healthcare Products Regulatory Agency （MHRA） method of disproportional method. ADR reports were described and classified according to the system organ class （SOC） and preferred term （PT） in Medical Dictionary for Regulatory Activities （24.0 edition）. RESULTS A total of 17 046 ADR reports related to the target drug melphalan were retrieved， and the number of ADR reports showed a fluctuating upward trend； the majority of patients were male （43.28%）， and were concentrated between the ages of 50-＜75 （35.09%）， with the main reporting country being the United States （23.97%）； ADR report involved a total of 22 842 severe outcomes， mainly including hospitalization or extended hospitalization （24.45%）. Totally 403 ADR signals were detected， involving 23 SOC， mainly including blood and lymphatic system diseases （801 cases， 13.77%）， followed by eye organ diseases （755 cases， 12.97%） and infectious and invasive diseases （716 cases， 12.30%）. The ADR signals ranked high in the number of reported cases included febrile neutropenia， diarrhea， fever and mucositis and other PT； PT such as pneumonia， sepsis， vitreous hemorrhage， chorioretinal atrophy， myelodysplastic syndrome were not recorded in drug instructions. The ADR signals with high signal strength ranking included choroidal dystrophy， chorioretinal atrophy， eyeball atrophy and other PT， and above three types of PT were not included in the drug instructions. CONCLUSIONS ADRs caused by melphalan mainly include blood and lymphatic system diseases， eye organ diseases， and infectious and invasive diseases； before using melphalan， it is necessary to evaluate the drug use of patients， and pay close attention to the patient’s blood indicators and eye toxicity reaction， so as to guarantee the safety of treatment.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: To explore the family rehabilitation model for children with scar contracture after hand burns and observe its efficacy. Methods: A retrospective non-randomized controlled study was conducted. From March 2020 to March 2021, 30 children with scar contracture after deep partial-thickness to full-thickness burns of hands, who met the inclusion criteria, were hospitalized in the Burn Center of PLA of the First Affiliated Hospital of Air Force Medical University. According to the rehabilitation model adopted, 18 children (23 affected hands) were included in a group mainly treated by family rehabilitation (hereinafter referred to as family rehabilitation group), and 12 children (15 affected hands) were included in another group mainly treated by hospital rehabilitation (hereinafter referred to as hospital rehabilitation group). In the former group, there were 11 males and 7 females, aged (4.8±2.1) years, who began rehabilitation treatment (3.1±0.8) d after wound healing; in the latter group, there were 7 males and 5 females, aged (4.6±2.1) years, who began rehabilitation treatment (2.8±0.7) d after wound healing. The children in hospital rehabilitation group mainly received active and passive rehabilitation training in the hospital, supplemented by independent rehabilitation training after returning home; after 1-2 weeks of active and passive rehabilitation training in the hospital, the children in family rehabilitation group received active and passive rehabilitation training at home under the guidance of rehabilitation therapists through WeChat platform. Both groups of children were treated for 6 months. During the treatment, they wore pressure gloves and used hand flexion training belts and finger splitting braces. Before treatment and after 6 months of treatment, the modified Vancouver scar scale, the total active movement of the hand method, and Carroll quantitative test of upper extremity function were used to score/rate the scar of the affected hand (with the difference of scar score between before treatment and after treatment being calculated), the joint range of motion (with excellent and good ratio being calculated), and the function of the affected limb, respectively. Data were statistically analyzed with independent sample t test, equivalence test, Fisher's exact probability test, and Mann-Whitney U test. Results: The differences of scar scores of the affected hands of children in family rehabilitation group and hospital rehabilitation group between after 6 months of treatment and those before treatment were 3.0 (2.0, 7.0) and 3.0 (2.0, 8.0) respectively (with 95% confidence interval of 2.37-5.38 and 1.95-5.91). The 95% confidence interval of the difference between the differences of the two groups was -2.43-2.21, which was within the equivalent boundary value of -3-3 (P<0.05). The excellent and good ratios of joint range of motion of the affected hand of children in family rehabilitation group and hospital rehabilitation group were 3/23 and 2/15 respectively before treatment, and 15/23 and 12/15 respectively after 6 months of treatment. The ratings of joint range of motion of the affected hand of children in family rehabilitation group and hospital rehabilitation group after 6 months of treatment were significantly higher than those before treatment (with Z values of 3.58 and 2.30, respectively, P<0.05), but the ratings of joint range of motion of the affected hand between the two groups were similar before treatment and after 6 months of treatment (with Z values of 0.39 and 0.55, respectively, P>0.05). The functional ratings of the affected limbs of children in family rehabilitation group and hospital rehabilitation group after 6 months of treatment were significantly higher than those before treatment (with Z values of 3.98 and 3.51, respectively, P<0.05), but the functional ratings of the affected limbs between the two groups were similar before treatment and after 6 months of treatment (with Z values of 1.27 and 0.38, respectively, P>0.05). Conclusions: The WeChat platform assisted rehabilitation treatment with mainly family rehabilitation, combined with hand flexion and extension brace can effectively reduce the scarring after children's hand burns, improve the joint range of motion of the affected hands, and promote the recovery of affected limb function. The effect is similar to that of hospital-based rehabilitation providing an optional rehabilitation, treatment method for children who cannot continue to receive treatment in hospital.
Male ; Female ; Humans ; Child ; Cicatrix/therapy* ; Retrospective Studies ; Treatment Outcome ; Wound Healing ; Hand Injuries/rehabilitation* ; Wrist Injuries ; Contracture/etiology* ; Burns/complications*

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*