1.First-in-class drug oroxylin A tablets for treating hepatic and gastrointestinal disorders: from preclinical development to clinical research.
Chengju LUO ; Xuhong LI ; Yuan GAO ; Junyi YANG ; Weiming FANG ; Libin WEI
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):801-814
Oroxylin A (OA) is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis. Currently, OA is obtainable through chemical synthesis and exhibits polypharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, and multi-organ protective effects. The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma (HCC) treatment. Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal (GI) disorders, including HCC, hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis, and colorectal cancer (CRC). OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism, and fibrosis activation. The oral pharmacokinetics of OA is characterized by phase II metabolism, hydrolysis, and enterohepatic recycling. This review provides a comprehensive overview of the critical stages involved in the development of OA tablets, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It encompasses the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and recent advancements in clinical trials. Importantly, this review examines the potential mechanisms by which OA may influence the gut-liver axis, hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.
Humans
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Flavonoids/pharmacokinetics*
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Tablets
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Animals
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Gastrointestinal Diseases/drug therapy*
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Liver Diseases/drug therapy*
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Drug Development
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Clinical Trials as Topic
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Scutellaria baicalensis/chemistry*
2.Up-regulation of Proinflammatory Cytokines in Rostral Ventromedial Medulla Contributes to Chronic Postsurgical Pain by Promoting 5-HT Release
Juanli DAI ; Zhen WANG ; Chaoxiong DONG ; Yuying LI ; Xuhong WEI
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):54-62
ObjectiveTo investigate the role of proinflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-1β (IL-1β) in rostral ventromedial medulla (RVM) in chronic postsurgical pain (CPSP) induced by skin/muscle incision and retraction (SMIR). MethodsSD rats were randomly divided into 5 groups: ① Sham group; ② SMIR group; ③ SMIR+TNFα/IL-1β neutralizing antibody group; ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold (MWT) was measured by the up-down method, immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine (5-HT) level. ResultsSMIR elicited persistent nociceptive sensitization, upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn. While microinjection of recombinant TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn. ConclusionUp-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.
3.Preparation of decellularized bone graft material with supercritical carbon dioxide extraction technique.
Feng HAO ; Kaifeng PAN ; Liuyun HUANG ; Xuhong CHEN ; Haikun WEI ; Xianhua CHEN ; Jianfeng ZHANG
Journal of Zhejiang University. Medical sciences 2024;53(6):772-778
OBJECTIVES:
To evaluate the immunogenicity and osteogenic ability of animal-derived bone graft material decellularized with supercritical carbon dioxide.
METHODS:
Porcine femurs were randomly divided into two groups after preliminary treatment, and decellularized with conventional method (control group) or supercritical carbon dioxide (experimental group). Allogenic demineralized bone matrix was used as positive control. Clearance rate of galactose-α-1, 3-galactose (α-Gal) antigen was determined by enzyme-linked immunosorbent assay and residual DNA was detected by a fluorescence method. Nine SPF-grade male athymic nude mice of 6 weeks old were randomly divided into experimental, control and positive control groups. Samples were implanted over biceps femoris muscle of athymic nude mice. The explants were collected 4 weeks post implantation. Hematoxylin and eosin (HE) staining and immunohistochemistry were applied to determine the osteogenic ability and bone tissue-associated protein expressions of the implants.
RESULTS:
The clearance rates of α-Gal antigen in the experimental group and the control group were (99.09±0.26)% and (30.18±2.02)%, respectively (t=58.67, P<0.01). The residual DNA of the experimental, control and positive control groups were (13.49±0.07), (15.20±0.21) and (14.70±0.17) ng/mg. The residual DNA in the experimental group was significantly lower than that in the control group (t=-13.41, P<0.01) and positive control group (t=-11.30, P<0.01). HE staining results showed that multiple bone formation centers with active osteogenesis and rich bone marrow were observed in experimental group 4 weeks after implantation, but only a small number of bone formation centers were observed in the control and positive control groups, with no obvious osteoblasts present. Immunohistochemistry results indicated that the expressions of alkaline phosphatase, Runt-related transcription factor 2, collagen typeⅠand osteocalcin in the experimental group showed an increasing trend compared with those in the control and positive control groups.
CONCLUSIONS
Compared with clinically used allogenic demineralized bone matrix and bone graft material decellularized with conventional method, bone graft material decellularized with supercritical carbon dioxide exhibits lower immunogenicity and better osteogenic ability.
Animals
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Mice
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Swine
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Male
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Bone Transplantation/methods*
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Mice, Nude
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Carbon Dioxide
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Osteogenesis/drug effects*
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Femur
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Bone Substitutes
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Tissue Engineering/methods*
4.Evaluation of the efficiency of medical resource utilization in public traditional Chinese medicine hospitals in Gansu province
Yuanyuan LI ; Mmetishawuti MIRIKAMIL ; Xuhong CHANG ; Xixin NIU ; Wei ZHOU
Chinese Journal of Hospital Administration 2023;39(3):206-209
Objective:To analyze the efficiency of medical resource utilization in public traditional Chinese medicine (TCM) hospitals in Gansu province from 2016 to 2020, so as to provide decision-making reference.Methods:The number of in-service staff, actual number of open beds, number of diagnosis and treatment, and number of discharge from TCM hospitals in Gansu province from 2016 to 2020 were extracted, and their technical efficiency, pure technical efficiency, scale efficiency, and returns to scale were analyzed by data envelopment analysis.Results:From 2016 to 2020, the average technical efficiency, pure technical efficiency, and scale efficiency of the sample hospitals were 0.647, 0.680, and 0.952, respectively. Among them, 213 hospitals (48.2%) were in a decreasing state of returns to scale, 54 hospitals (12.2%) were in a constant state of returns to scale, and 175 hospitals (39.6%) were in an increasing state of returns to scale; Out of the 45 tertiary hospitals, 42 (93.3%) were in the stage of diminishing returns to scale, while 226 (56.9%) of 397 secondary and lower hospitals were in a state of constant or increasing returns to scale.Conclusions:The utilization efficiency of medical resources in public TCM hospitals in Gansu province is relatively low, and there is a significant gap between different levels of TCM hospitals.
5.Research progress in mahjong epilepsy
Qiuyan TANG ; Xiaofeng WEI ; Qian FENG ; Huizhong YANG ; Xuhong YANG
Chinese Journal of Primary Medicine and Pharmacy 2023;30(10):1597-1600
Reflex epilepsy is a type of partial or generalized seizure induced by specific or nonspecific stimulation in individuals without a prior history of seizures. Mahjong epilepsy is a special form of complex reflex epilepsy induced by playing or watching mahjong, with a low incidence rate and complex pathogenesis. Due to the lack of comprehensive understanding, clinical studies of mahjong epilepsy are still mainly based on case reports. Now, we will analyze and summarize the etiology, pathogenesis, clinical diagnosis, electroencephalogram, treatment, and prognosis of mahjong epilepsy to raise awareness of mahjong epilepsy among clinical medical workers.
6.Establishment of screening models for nonalcoholic fatty liver disease in the adult Blang population
Yebei LIANG ; Chunguang YANG ; Huadong ZENG ; Ruwei TAO ; Qiuming HU ; Xiaoying TANG ; Huaxiang SHI ; Wei WU ; Xuhong HOU ; Weiping JIA
Journal of Clinical Hepatology 2021;37(12):2861-2868
Objective To establish simple screening models for nonalcoholic fatty liver disease (NAFLD) in the adult Blang population. Methods Based on the survey data of metabolic diseases in the Blang people aged 18 years or above in 2017, 2993 respondents were stratified by sex and age (at an interval of 5 years) and then randomly divided into modeling group with 1497 respondents and validation group with 1496 respondents. Related information was collected, including demographic data, smoking, drinking, family history of diseases and personal medical history, body height, body weight, waist circumference, and blood pressure, and related markers were measured, including fasting plasma glucose, 2-hour postprandial plasma glucose or blood glucose at 2 hours after glucose loading, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase. The chi-square test was used for comparison of categorical data between two groups. Logistic regression analysis was used to establish the screening model. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value were used to evaluate the screening performance of established models versus existing models in the study population, and the DeLong method was used for comparison of AUC. Results Three screening models for NAFLD were established based on physical and biochemical measurements, i.e., simple noninvasive model 1 (age, body mass index, and waist circumference), noninvasive model 2 with the addition of blood pressure, and model 3 with the combination of hematological parameters (diabetes and ALT/AST). In the modeling group, the three models had an AUC of 0.881 (95% confidence interval [ CI ]: 0.864-0.897), 0.892 (95% CI : 0.875-0.907), and 0.894 (95% CI : 0.877-0.909), respectively, and there was a significant difference between model 1 and models 2/3 ( P =0.004 0 and P < 0.001); in the validation group, the three models had an AUC of 0.891 (95% CI : 0.874-0.906), 0.892 (95% CI : 0.875-0.907), and 0.893 (95% CI : 0.876-0.908), respectively, and there was no significant difference between the three groups ( P > 0.05). Based on the overall consideration of screening performance, invasiveness, and cost, the simple noninvasive model 1 was considered the optimal screening model for NAFLD in this population. Model 1 had the highest Youden index at the cut-off value of 5 points, and when the score of ≥5 points was selected as the criteria for NAFLD, the model had a sensitivity of 86.5%, a specificity of 79.7%, a positive predictive value of 50.3%, and a negative predictive value of 96.1% in the modeling group and a sensitivity of 85.6%, a specificity of 80.6%, a positive predictive value of 51.7%, and a negative predictive value of 95.8% in the validation group. Conclusion The NAFLD screening models established for the adult Blang population based on age and obesity indicators have relatively higher sensitivity, specificity, and negative predictive value, and this tool is of important practical significance for the intervention of NAFLD and its closely related metabolic diseases in this population.
7.Incidence of unintended pregnancy within 2 years after delivery and its influencing factors in China
Caixia YANG ; Xuhong ZHAO ; Yuyan LI ; Yanfei ZHOU ; Lin'ai ZHANG ; Dong YUAN ; Wei XIA ; Jianmei WANG ; Jiandong SONG ; Wen LYU ; Yongfeng LUO ; Lifang JIANG ; Li JIANG ; Xiaochen HUANG ; Xiaoyu HU ; Xiaojing DONG ; Tongyin CHENG ; Yuanzhong ZHOU ; Yan ZHANG ; Yan CHE
Chinese Journal of Obstetrics and Gynecology 2021;56(9):616-621
Objective:To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China.Methods:Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women′s socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis.Results:A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95% CI: 4.5%-6.1%) and 13.1% (95% CI: 11.3%-14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions:In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.
8.Investigation on the application and retention of intravenous infusion tools in hospitalized children
Chunli WANG ; Xuhong WU ; Jianhui XIE ; Xiaoyan NIE ; Jiejing DONG ; Xinyi WU ; Wei WANG ; Qun XU ; Quelan HUANG ; Linqi ZHANG ; Lili LIU
Chinese Journal of Modern Nursing 2020;26(1):16-20
Objective:To investigate the use of different tools of intravenous infusion and the issues associated with intravenous catheter indwelling in hospitalized children and to provide reference for clinical practices.Methods:Using the convenient sampling method, from July 24th to 31st, 2018, the intravenous infusion treatment of children inpatients in 49 hospitals within the Beijing Children's Hospital Medical Association was selected for investigation. A self-designed Cross-sectional Questionnaire for Children's Intravenous Infusion and a photo of an intravenous infusion tool were used for data collection. Statistical analysis was performed using SPSS 17.0 software.Results:During the data collection period, there were 18 316 hospitalized children in the 49 hospitals, among which there were 14 421 cases of infusions, with the infusions rate of 78.73%. The application rate of indwelling needle was 87.94%. The connector of venous catheter was mainly heparin cap connection (64.23%) . The infusion tools used in 6 398 cases (44.37%) were made by PVC and containing 2-ethyl hexyl phthalate (DEHP) . Aseptic transparent dressing was the main dressing choice. During catheter indwelling, there were some problems such as back-blood in the pipeline or infusion joint, incorrect clamping position of small clips, unclamping, and tube detachment. Indwelling needles had more problems than central venous catheters, including old blood returning in the tube and blood returning in the infusion connector. The difference between the peripheral indwelling needle and the central catheter was statistically significant ( P<0.05) . Conclusions:The rate of intravenous infusion in hospitalized children is relatively high. Although there are various types of intravenous infusion tools, the choice of infusion tools for children was mainly indwelling needle and heparin cap connection, and there were still room for improvement in catheter maintenance.
9.Prevalence of diabetes and its associated factors in Blang ethnic adults
Yebei LIANG ; Xuhong HOU ; Wei WU ; Yanhui LI ; Huaxiang SHI ; Kunfeng WANG ; Xiaoying TANG ; Weiping JIA
Chinese Journal of Internal Medicine 2019;58(1):27-32
Objective To investigate the prevalence and associated risk factors of diabetes and prediabetes in Blang ethnic adults in Menghai county. Methods A cross-sectional survey including 3 365 Blang ethnic adults (aged 18 and above from 5 administrative villages) was conducted from February 2017 to March 2017 in Menghai county. A questionnaire, physical examination, and blood assays were included in the survey. Finally,a total of 3 237 adults with complete data were selected into this analysis. Results The standardized prevalence of diabetes and prediabetes in Blang ethnic adults were estimated based on the sixth national census in 2010. According to the 1999 WHO criteria, the overall standardized prevalence of diabetes and prediabetes were 8.5% (men: 10.2%, women: 6.8%) and 16.1% (men: 18.0%, women: 14.1%), in which the standardized prevalence of newly diagnosed diabetes among the total population was 7.3% (men: 8.7%, women: 5.8%). Multivariable multinominal logistic regression analyses showed that age, hypertension, hypertriglyceridemia, and central obesity were significantly positively associated with both diabetes and prediabetes, with the corresponding odds ratios of 1.74 and 1.37, 2.39 and 2.02, 2.30 and 1.34, 2.55 and 1.73, respectively. Conclusion The prevalence of diabetes is relatively high in Blang ethnic adults in Menghai county. Improving knowledge of diabetes among the local population is one of key steps in the prevention of diabetes.
10.1H-MRS detection of metabolites in posterior cingulate gyrus of Parkinson disease with cognitive impairment patients
Mingming HUANG ; Wei PU ; Xuhong LI ; Ling JIAO ; Hui YU
Chinese Journal of Medical Imaging Technology 2018;34(3):326-330
Objective To investigate the value of 1H-MRS technology combined with linear combination model (LCmodel) software in diagnosis of Parkinson disease (PD) cognitive impairment.Methods Thirty-five PD patients (PD group) and 22 matched healthy subjects (control group) were collected.Patients in PD group were divided into PDN and PDMCI subgroups according to whether having cognitive impairment or not.The concentration of metabolites of posterior cingulate gyrus (PCG)was applied with 1H-MRS technology combined with LCmodel software.The differences of metabolites were compared between the two groups,and the correlations between metabolites level and cognitive status were analyzed.Results The absolute concentrations of metabolites in PDN subgroup were not significantly different from those in control group (all P>0.05).The absolute concentrations of total creatine (tCr),N-acetyl aspartate (NAA),myo-inositol (mI) and glycerophosphocholine+ phosphocholine (tCho) in PDMCI subgroup were lower than those in control group (all P<0.05).The absolute concentration of tCr in PDMCI subgroup was lower than that in PDN subgroup (P<0.05).There was positive correlation among the absolute concentration of tCr (r=0.444,P=0.01),glutathione (GSH;r=0.393,P=0.024) and MMSE scores,as well as among the absolute concentration of tCr (r=0.367,P=0.035),GSH (r=0.376,P=0.031),tCho (r=0.375,P=0.031) and MoCA scores.Conclusion 1 H-MRS technology combined with LCmodel software can quantitatively analyze the changes of metabolites in PCG,therefore being helpful to evaluating PD cognitive impairment.

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