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

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P<0.01), indicating the successful establishment of ASO. Moreover, the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased (P<0.05), while the IL-10 level was significantly decreased (P<0.05). In addition to increased IL-6 and IL-17 levels, the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group. The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased (P<0.05). These alternations were also observed in ASO patients. After endovascular surgery (such as percutaneous transluminal angioplasty and arterial stenting), all these changes were significantly improved (P<0.05). Conclusions: The Th17/Treg and M1/M2 ratios were significantly increased in ASO, and surgery can effectively improve the balance of Th17/Treg, and reduce the ratio of M1/M2, and the expression of inflammatory factors.

Objective To investigate the expression of prolyl 4-hydroxylase β-polypeptide(P4HB)in glioblastoma multiforme(GBM)and its impact on clinical prognosis,as well as on the proliferation and migration of U87 cells.Methods(1)According to the Cancer Genome Atlas(TCGA)database,GTEx database and GEPIA2 database,the difference expression of P4HB in GBM and normal brain tissues were analyzed by R software.(2)A total of 52 patients with GBM who underwent surgical treatment from February 2017 to December 2019 were collected from Department of Neurosurgery,the Second People's Hospital of Guiyang.The normal brain tissues of 10 patients were selected as controls.Immunohistochemical method was used to detect the expression level of P4HB in tumor tissues and normal tissues.The Kaplan-Meier method with the log-rank test was employed for survival analysis.Receiver operating characteristic(ROC)curve was used to analyze the predictive valuable of P4HB expression in survival rate of GBM.Univariate and multivariate Cox regression analysis were used to identify the expression of P4HB and related clinicopathological factors affecting the survival and prognosis of the patients.(3)Human GBM U87 cells were randomly assigned into three groups:control group,NC-siRNA group and P4HB-siRNA group.P4HB expression was interfered with by the transfection of siRNA in P4HB-siRNA group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the content of P4HB mRNA in U87 cells.Cell counting kit-8(CCK-8)and immunofluorescence assay were used to analyze the effects of P4HB on the proliferation of U87 cells.Scratch test was used to analyze the effects of P4HB on cell migration.Results The expression of P4HB was significantly upregulated in GBM tissues compared with normal brain tissues(P<0.05).The γδ T cells(r=-0.227)and follicular helper T cells(r=-0.226)were negatively correlated with the expression of P4HB,while natural killer cell(r=0.417),macrophages(r=0.374),neutrophils(r=0.344),and immature dendritic cells(r=0.263)were positively correlated with the expression of P4HB.Kaplan-Meier survival analysis showed that the progression-free survival and disease-specific survival of GBM patients with high P4HB expression were significantly lower than those with low expression(P<0.05).ROC curve showed that the area under the curve(AUC)of P4HB in predicting overall survival rate of GBM patients was 0.982,and 1-year,3-year,and 5-year survival was 0.655,0.724,0.861,respectively.The immunohistochemistry results suggested that P4HB protein was significantly highly expressed in GBM tumors.Survival analysis indicated that high expression of P4HB was associated with bad prognosis in GBM patients(P<0.05).Multivariate Cox regression analysis indicated that high expression of P4HB and TERT promoter mutations were the independent prognostic risk factors for GBM(P<0.05).Compared with control group and NC-siRNA group,the expression levels of P4HB were decreased significantly after transfected with siRNA in U87 cells of P4HB-siRNA group(P<0.01),and the proliferation ability and the wound healing rate were decreased significantly in P4HB-siRNA group(P<0.001).Conclusions P4HB is significantly highly expressed in GBM,which indicates that the prognosis of patients is poor.Knockout of P4HB could inhibit cellular proliferation and migration of GBM U87 cells.P4HB may be used as the relevant predictive marker and potential therapeutic target in GBM.

Objective To explore the application value of compressed sensing(CS)combined with deep learning(DL)reconstruction techniques for orbital MRI.Methods Thirty healthy individuals were selected to undergo MRI scanning with parallel imaging(S group with an acceleration factor of 2)and CS imaging(CS group with acceleration factors of 2,3,4 and 5),and images were acquired after DL reconstruction(DL group involving in S2DL,CS2DL,CS3DL,CS4DL and CS5DL sequences).All the groups were compared in terms of the subjective indexes including overall image quality,clarity of musculi oculi boundaries and diagnostic confidence level and the objective indexes including oculomotor-temporal muscle signal intensity ratio(SIR),oculomotor signal to noise ratio(SNR)and oculomotor-temporal muscle contrast to noise ratio(CNR).SPSS 26.0 statistical software was used for data analysis.Results S and CS groups after DL image reconstruction had the scores of the subjective indexes enhanced,and the differences of the subjective indexes between CS2 and S2,CS2DL and S2DL,CS2 and CS2DL were not statistically significant(P＞0.05);CS3 and CS2,CS5 and CS5DL did have significant differences in the overall image quality and clarity of musculi oculi boundaries(P＜0.05),while CS2DL and CS3DL did not(P＞0.05);there were significant differences in overall image quality,clarity of musculi oculi boundaries and diagnostic confidence level between CS3 and CS3DL and between CS4 and CS4DL.For the objective indexes,S and CS groups after image DL reconstruction had the scores of oculomotor SNR and oculomotor-temporal muscle CNR increased,and CS2,S2,CS2DL and S2DL had statistically significant differences in oculomotor SNR and oculomotor-temporal muscle CNR(P＜0.05);DL and CS groups were not significantly different in oculo-motor-temporal muscle SIR(P＞0.05).Conclusion DL reconstruction technique improves iamge quality while enhancing the image SNR and CNR.CS with an acceleration of 3 combined with DL reconstruction technique contibutes to shortening scanning time,strengthening image quality and bettering patient satisfaction,which is of great application value for orbital MRI.[Chinese Medical Equipment Journal,2024,45(10):60-65]

The distal tibial epiphyseal fractures is a common type of fracture in adolescents.The distal tibia is adjacent to the ankle joint,where the epiphysis is fragile and easily damaged when the fracture occurs,resulting in ischemic necrosis of the epiphysis and impaired bone growth,and the degree of damage and treatment effect directly influence the shape and function of the ankle joint,seriously affect the prognosis and quality of life of adolescents.Therefore,anatomical reduction should be achieved after injury as much as possible to achieve stable fixation.For stable fractures of the distal tibial epiphysis(such as Salter-Harris type Ⅰ or Ⅱ fractures),the conservative treatment can be used;whereas for unstable fractures,especially Salter-Harris type Ⅲ and Ⅳ fractures with a high risk of displacement,surgical treatment is preferred.However,due to the physiological characteristics of the epiphysis of adolescents,the distal tibia grow and develop differently,the individualized treatment plans should be developed according to the situation of adolescents.3D printing technology combined with imaging technologies including CT and MRI can print complex shapes of geometric structures to meet individual needs,and play an important role in the surgical treatment of distal tibial epiphyseal fractures,especially Salter-Harris type Ⅲ and Ⅳ fractures,which can contribute to formulating individualized surgical plans,improving the success rate of surgery,reducing the incidence of long-term complications,and greatly improving the prognosis of adolescents.Based on the literature reports in the past decade,this paper reviews the research progress of the application of 3D printing technology in the diagnosis and treatment of distal tibial epiphyseal fractures in adolescents.

Objective To evaluate the safety and efficacy of intravascular lithotripsy(IVL)in the treatment of coronary artery calcification lesions.Methods A total of 53 patients who underwent endovascular imaging guided treatment of coronary artery calcified lesions with either IVL or cutting balloon(CB)at the Affiliated Hospital of Jining Medical College from January 2023 to July 2023 were retrospectively analysed(IVL:n=18,CB:n=35)were retrospectively analysed to compare the technique,clinical success rate,major adverse cardiovascular events(MACE)and readmission for cardiovascular events in patients followed during hospitalisation and 1 month after the procedure.Results Clinical success rates were identical in the IVL and CB groups(100.0％vs.100.0％,P＞0.999),the minimum lumen area of lesions was similar in the VL and CB groups[(1.7±0.4)mm2 vs.(1.7±0.5 mm2),P=0.628].And there was a statistically significant difference in the overall mean lesion length between the IVL and CB groups[(28.4±9.6)mm vs.(20.9±8.6)mm,P=0.008].During the procedure,there were no complications such as aneurysm,thrombus,or emergency vessel closure.There was a statistically significant difference in the overall mean value of residual stenosis between the IVL and CB groups[(1.7±1.7)％vs.(6.9±2.0)％,P=0.049].There were no MACE in either group during hospitalisation or at the one-month follow-up(0 vs.0,P＞0.999),and 3 patients in the CB group were readmitted for angina pectoris(0 vs.8.6％,P=0.543),with no significant difference in readmission rates between the two groups.Conclusions The technique of intravascular lithotripsy is safe and effective in the treatment of coronary artery calcification lesions.

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.
Humans ; Middle Aged ; Aged ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Prospective Studies ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To analyze the epidemic characteristics and drug resistance of pulmonary tuberculosis among the floating population in Beijing and to provide a scientific basis for formulating strategies for the prevention and control of tuberculosis among the floating population. Methods: Data of tuberculosis patients who were positive for Mycobacterium tuberculosis culture was collected from 16 districts and one municipal institution of tuberculosis control and prevention in Beijing in 2019. The strain samples were tested for drug sensitivity by the proportional method. According to household registration location, patients were divided into the floating population and Beijing registration. SPSS 19.0 software analyzed tuberculosis patients' epidemic characteristics and drug resistance in the floating population. Results: In 2019, there were 1 171 culture-positive tuberculosis patients in Beijing, among the floating population, 593 (50.64%) patients were identified, with a male-to-female sex ratio of 2.2∶1 (409∶184). Compared to patients under household registration as Beijing residents, a higher proportion of young adults aged 20-39 years (65.09%,386/593) were noticed, with 55.65% (330/593) reported from the urban areas and 96.80% (574/593) were reported the first time. The differences were statistically significant (all P<0.05). After completing the drug sensitivity test, 37 cases were with multiple drug-resistant tuberculosis, accounting for 6.24% (37/593). The rates of isoniazid resistance (42.11%,8/19) and multidrug resistance (21.05%,4/19) in floating population patients after retreatment were significantly higher than those in newly treated patients (11.67%, 67/574 and 5.75%, 33/574), and the differences were statistically significant (all P<0.05). Conclusions: Most patients with tuberculosis in the floating population in Beijing in 2019 were young males aged 20-39 years. The reporting areas were urban areas and the newly treated patients mainly. The patients with tuberculosis in the re-treated floating population were more likely to suffer from multidrug and drug resistance, which should be taken as the key population for prevention and control.
Young Adult ; Humans ; Female ; Male ; Beijing/epidemiology* ; Tuberculosis ; Tuberculosis, Pulmonary/epidemiology* ; Tuberculosis, Multidrug-Resistant/epidemiology* ; Drug Resistance