1.Protective Effect against Helicobacter pylor Gastritis in Mice by Flavonoid Combinations of Alpiniae Officinarum Rhizoma via Inhibition of PI3K/Akt Pathway
Xin LUO ; Wuyinxiao ZHENG ; Jingyu YANG ; Jianting ZHAN ; Haoran MA ; Xiaochuan YE ; Guopin GAN ; Dan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):61-68
ObjectiveTo investigate the protective effect and mechanism of action of flavonoid combination of Alpiniae Officinarum Rhizoma (A. officinarum) against Helicobacter pylori (H. pylori) gastritis in mice. MethodsAfter acclimatization for one week, 56 SPF-grade healthy C57BL/6J mice were gavaged with mixed antibiotics for three consecutive days. They were randomly divided into a normal group, model group, positive drug group (triple therapy group), and low- and high-dose groups (100, 200 mg·kg-1) of flavonoid combination of A. officinarum. The H. pylori gastritis mice model was established by gavage with H. pylori bacterial suspension in each group except for the normal group. After successful modeling, mice were administrated with corresponding drugs once a day for two weeks. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in gastric tissue. Rapid urease test paper was used to detect the positive rate of H. pylori. Silver staining was used to observe the H. pylori adherence on the surface of gastric tissue. Immunohistochemistry was used to detect the protein expression of interleukin-8 (IL)-8 and myeloid differentiation factor (MyD88) in gastric tissue. The serum levels of IL-6, tumor necrosis factor-α (TNF-α), IL-8, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) protein were detected by Western blot. ResultsCompared with those in the normal group, mice in the model group had lower gastric weight coefficients, higher pH of gastric juice, 100% H. pylori infection rate, and significantly changed gastric histopathology. The expressions of IL-8 and MyD88 proteins in the gastric tissue of mice in the model group were significantly elevated, and the serum levels of inflammatory factors IL-6, TNF-α, IL-8, and IL-1β were significantly up-regulated in mice. Compared with that in the model group, the gastric weight coefficient of mice in each treatment group of the flavonoid combinations of A. officinarum was elevated (P<0.01), and the pH of gastric juice was reduced (P<0.01). The infection rate of H. pylori was reduced. The expressions of IL-8 and MyD88 proteins in the gastric tissue of mice in the treatment groups were significantly reduced (P<0.01), and the serum levels of inflammatory factors IL-6, TNF-α, IL-8, and IL-1β were significantly reduced in a dose-dependent manner (P<0.01). The flavonoid combinations of A. officinarum down-regulated the expression of PI3K and Akt proteins in H. pylori gastritis-infected cells (P<0.01). ConclusionThe protective effect of flavonoid combinations of A. officinarum against H. pylori gastritis is associated with the inhibition of H. pylori infection rate and regulation of PI3K/Akt signaling pathway, resulting in inhibiting the release of inflammatory factors.
2.Efficacy and safety of hyperthermic intraperitoneal chemotherapy combined with immune checkpoint inhibitors in treatment of gastric cancer with ascites
Haitao LI ; Tongfei WANG ; Shuangyan ZHANG ; Hong XU ; Tian XU ; Fan YANG ; Lei WU ; Haoran ZHENG ; Biaofei YE
Cancer Research and Clinic 2024;36(11):852-857
Objective:To investigate the efficacy and safety of hyperthermic intraperitoneal chemotherapy combined with immune checkpoint inhibitors in treatment of gastric cancer with ascites.Methods:A retrospective case-control study was conducted. The clinical data of 39 gastric cancer patients with malignant ascites treated in Xi'an Third Hospital from May 2021 to June 2023 were retrospectively analyzed. All patients were divided into the routine group (18 cases) and the observation group (21 cases) according to different treatment methods. The patients in the routine group were treated with hyperthermic intraperitoneal chemotherapy combined with systemic intravenous chemotherapy; the patients in the observation group were treated with immune checkpoint inhibitors on the basis of hyperthermic intraperitoneal chemotherapy combined with systemic intravenous chemotherapy. The clinical efficacy, tumor marker levels, Karnofsky scores, and incidence of adverse reactions of both groups were compared. Kaplan-Meier method was used to analyze the overall survival (OS) of both groups.Results:There were 12 males (66.7%) and 6 females (33.3%) in the routine group, with the age of (57±13) years; 13 males (61.9%) and 8 females (38.1%) in the observation group, with the age of (59±12) years. After treatment, the serum carcinoembryonic antigen (CEA), carbohydrate 125 (CA125), carbohydrate 199 (CA199) levels in the 2 groups were lower than those before treatment, and the differences were statistically significant (all P < 0.05). After treatment, the serum CEA, CA125, CA199 levels in the observation group were lower than those in the routine group, and the differences were statistically significant (all P < 0.05). After treatment, Karnofsky scores in the observation group were higher than those before treatment [(78.6±7.5) scores vs. (69.5±8.9) scores], and Karnofsky scores in the observation group were higher than those in the routine group [(78.6±7.5) scores vs. (72.8±7.9) scores],and the differences were statistically significant ( t = -3.65, 2.33, all P < 0.05). The objective remission rate (ORR) was 55.6% (10/18) and 71.4%(15/21), respectively in the routine group and the observation group, and the difference was statistically significant ( χ2 = 9.24, P = 0.002). The median OS time was 38.97 months (95% CI: 34.99-42.95 months) and 23.62 months (95% CI: 18.49-28.74 months), respectively in the observation group and the routine group, and the difference was statistically significant ( χ2 = 3.88, P = 0.049). There was no statistically significant difference in the incidence of adverse events between the 2 groups (all P > 0.05). No serious treatment-related complications were found in the observation group. Conclusions:Hyperthermic intraperitoneal chemotherapy combined with immune checkpoint inhibitors shows a good therapeutic effect in the treatment of gastric cancer with ascites, and the adverse reactions are controllable.
3.Screening of Anti-Helicobacter pylori Gastritis Active Component of the Ethyl Acetate Extract of Alpinia officinarum Hance Based on the Knockout Strategy
Xin LUO ; Wuyingxiao ZHENG ; Jianting ZHAN ; Jingyu YANG ; Haoran MA ; Guoping GAN ; Pengtao YOU ; Xiaochuan YE ; Dan LIU
Herald of Medicine 2024;43(9):1387-1392
Objective To screen the anti-Helicobacter pylori gastritis active components of the ethyl acetate extract of Alpinia officinarum Hance.Methods The"knock-out"strategy combined with high-performance liquid chromatography(HPLC)detection was developed to separate the components of the ethyl acetate extract of A.officinarum while obtaining the negative samples without the components.A human gastric epithelial cell(GES-1)model of H.pylori gastritis was established,and the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)and interleukin-1β(IL-1β)in the supernatant of the cells were determined by enzyme-linked immunosorbent assay(ELISA).Results The total flavonoid fraction,the negative fraction without total diphenylheptanoids,the negative fraction without 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA),and galangin significantly reduced IL-6 levels in the supernatant of H.pylori infected GES-1 cells at a concentration of 8 μg·mL-1 with 24 h incubation.The total flavonoid fraction strongly inhibited the release of IL-6,TNF-α,IL-8,and IL-1β from H.pylori gastritis GES-1 cells at a concentration of 16 μg·mL-1.Conclusions The total flavonoid fraction is the major anti-H.pylori gastritis active component of the ethyl acetate extract of A.officinarum.The results lay the foundation for further elucidation of the material basis of A.officnarum against H.pylori gastritis.
4.A survey report on the status of emergency radiology in China
Jing WANG ; Zheng MIAO ; Qi YANG ; Lei ZHANG ; Hao WANG ; Huishu YUAN ; Haoran SUN ; Wei JIANG ; Yuan TIAN ; Mingyang LI ; Yaning WANG ; Zhaoyi MA ; Huimao ZHANG
Chinese Journal of Radiology 2024;58(6):661-666
Objective:To investigate the application status of emergency radiology in China, and to provide data support for the standardized development, scientific management and big data research of emergency radiology.Methods:From August 12th to October 19th, 2022, a questionnaire survey was conducted through WeChat"Questionnaire Star"to send targeted questionnaires to investigate the relevant data of the current status of emergency radiology in China, mainly including digital radiography (DR) and computed tomography (CT). This study was initiated by the Chinese Emergency Radiology Database Collaboration Group, and comprehensively investigated emergency imaging personnel, equipment, workload, critical value reporting process, and artificial intelligence (AI) application status.Results:There were 123 hospitals in the study. The survey showed that emergency DR/CT reports were mainly completed by residents and above (69.1%). There were 21 DR brands, 10 CT brands and 8 MR brands used for emergency imaging examinations. The median number of DR examinations in tertiary hospitals and secondary hospitals investigated from January to June 2022 was 4 642 and 2 015 cases respectively, and the median number of CT examinations was 16 512 and 3 762 cases respectively. The average single-shift workload of DR in the emergency radiology department during the day and night shift in tertiary hospitals was mainly ≤20 copies and 21-50 copies, and the average single-shift workload of CT in the emergency radiology department during the day and night shift was mainly 21-50 copies and 51-100 copies, while the average single-shift workload of DR/CT in the emergency radiology department during the day/night shift in secondary hospitals was mainly ≤20 copies. In terms of critical value reporting process, 74.8% of emergency imaging doctors and 84.6% of emergency imaging technicians took the way of phone/text message to notify the clinical doctor or the patients′ family. The overall deployment rate of AI in emergency imaging was about 60.2%. 75% of the respondents believed that in the future, AI can improve emergency radiology work from aspects such as emergency screening, aided diagnosis and process optimization.Conclusions:The emergency medical imaging mainly based on DR and CT has the current situations such as generally low seniority of doctors, diverse brands of imaging equipments, large volume of examinations and intense workload per doctor, especially in tertiary hospitals, and dependence on traditional means for critical value reporting. At present, AI is emerging in the field of emergency imaging, and there is still a long way to go to play the huge potential of AI in the intelligent whole process of emergency imaging in the future.
5.Urolithin A mediates p38/MAPK pathway to inhibit osteoclast activity
Haoran HUANG ; Yinuo FAN ; Wenxiang WEI-YANG ; Mengyu JIANG ; Hanjun FANG ; Haibin WANG ; Zhenqiu CHEN ; Yuhao LIU ; Chi ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(8):1149-1154
BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.
6.Relationship between preoperative serum bilirubin concentration and postoperative delirium in patients undergoing knee or hip replacement
Shuhui HUA ; Mengya ZHANG ; Shanling XU ; Yunchao YANG ; Haoran ZHANG ; Chuan LI ; Yanan LIN ; Rui DONG ; Hongyan GONG ; Xu LIN ; Yanlin BI ; Bin WANG
Chinese Journal of Anesthesiology 2024;44(3):286-291
Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.
7.Correlation of early neurodevelopmental features of children with SYNGAP1 variants and their genotypes
Haoran LIU ; Shenghai YANG ; Jiayi LI ; Hua XIE ; Xiaoli CHEN
Chinese Journal of Medical Genetics 2024;41(1):25-31
Objective:To explore the early neurodevelopmental features of young children with SYNGAP1 variants and their genotype-phenotype correlation. Methods:Young children with neurodevelopmental disorders (NDDs) (< 5 years old) who were referred to the Children′s Hospital Affiliated to the Capital Institute of Pediatrics between January 2019 and July 2022 were selected as the study subjects. All children had undergone whole-exome sequencing, comprehensive pediatric neuropsychological assessment, familial segregation analysis, and pathogenicity classification. Meanwhile, young Chinese NDD children (< 5 years old) with pathogenic/likely pathogenic SYNGAP1 variants were retrieved from the literature, with information including detailed clinical and genetic testing, neurodevelopmental quotient (DQ) of the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). Children who did not have a detailed DQ but had their developmental status assessed by a medical professional were also included. The correlation between neurodevelopmental severity, comorbidity and SYNGAP1 variants were summarized. Results:Four young NDD children carrying SYNGAP1 variants were recruited (1 male and 3 females, with a mean age of 34.0 ± 18.2 months), among whom one harboring a novel variant (c.437C>G, p. S146*). Combined with 19 similar cases retrieved from the literature, 23 Chinese NDD young children were included in our study (8 males and 10 females, 5 with unknown sex, with a mean age of 37.1 ± 14.2 months). A loss of function (LOF) variant was found in 19 (82.6%) children. All of the children had presented global developmental delay (GDD) before the age of two. In addition, 16 (69.6%) had seizure/epilepsy at the age of 27.0 ± 12.1 months, among whom 15 had occurred independent of the global developmental delay. Myoclonic and absence were common types of seizures. Compared with those with variants of exons 8 to 15, the severity of developmental delay was milder among children with variants in exons 1 to 5. Conclusion:The early neurodevelopment features of the SYNGAP1 variants for young children (< 5 years old) have included global developmental delay and seizure/epilepsy. All of the children may present GDD before the age of two. The severity of developmental delay may be related to the type and location of the SYNGAP1 variants.
8.Assessment of the health situation of daily learning time for elementary school students in the context of Double Reduction policy
YANG Haoran, LI Jin, LIU Kaiqi, TU Ying, LI Suyun, YANG Xiao, LEI Suwen, LI Jing
Chinese Journal of School Health 2024;45(9):1354-1358
Objective:
To investigate the daily learning time status of elementary school students and understand the implementation of Health Requirements of Daily Learning Time for Secondary and Elementary School Students (GB/T 17223-2012) in schools, so as to provide a reference for strengthening and improving school health and health education in the new era.
Methods:
A stratified cluster random sampling method was used to select 7 776 primary school students in Shandong Province, and a survey questionnaire was designed based on the Health Requirements for Dayily Learning Time for Secondary and Elementary School Students(GB/T 17223-2012) standard to investigate their daily learning arrangements, sleep and physical activities, and breaks between classes. Comparison of intergroup differences were used by Chi square test and Kruskal-Wallis H test.
Results:
About 55.88 % of primary school students for daily learning time met the standard. There was a statistically significant difference in the daily learning time achievement rate among primary school students in three grades for first and second grade, third and fourth grade and fifth and sixth grade ( Z=1 629.47, P <0.01), and the fifth and sixth grade had the highest proportion of achieving the standard (85.92%). Specifically, the proportions of students whose class hours, class numbers and morning reading time meeting the standards were 30.07%, 10.20% and 42.19%, respectively. The sleep deficiency rate of primary school studnets was 58.69%, and the physical activity deficiency rate was 65.78%; and there was a statistically significant difference in the rate of insufficient sleep time and physical activity time among primary school students of different grades ( χ 2=56.39, 95.95, P <0.01), with sixth grade students showing the highest rates for both sleep and physical activity deficiencies (64.35%, 73.37%). Additionally, 49.78% of students had recess time below the standard requirements.
Conclusion
The health status of daily learning time among primary school students in Shandong Province is poor, with insufficient implementation of school standards, and the implementation of standards needs to be further strengthened.
9.Application of computer-aided design modified 3D printing model in video-assisted thoracoscopic sublobular resection for early lung cancer: A retrospective cohort study
Xinyu ZHANG ; Linqian LI ; Haoran LI ; Qiang GUO ; Hongli YAN ; Jinghua LI ; Shujie CHENG ; Hefei LI ; Ke ZHANG ; Jihong YANG ; Jianguo WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(09):1266-1273
Objective To compare the effect of three-dimensional visual (3DV) model, three-dimensional printing (3DP) model and computer-aided design (CAD) modified 3DP model in video-assisted thoracoscopic surgery (VATS) sublobular resection. Methods The clinical data of patients who underwent VATS sublobular resection in the Affiliated Hospital of Hebei University from November 2021 to August 2022 were retrospectively analyzed. The patients were divided into 3 groups including a 3DV group, a 3DP group and a CAD-3DP group according to the tools used. The perioperative indexes and subjective evaluation of operators, patients and their families were compared. Results A total of 22 patients were included. There were 5 males and 17 females aged 32-77 (56.95±12.50) years. There were 9 patients in the 3DV group, 6 patients in the 3DP group, and 7 patients in the CAD-3DP group. There was no statistical difference in the operation time, intraoperative blood loss, drainage volume, hospital stay time or postoperative complications among the groups (P>0.05). Based on the subjective evaluations of 4 surgeons, the CAD-3DP group was better than the 3DV group in the preoperative planning efficiency (P=0.025), intuitiveness (P=0.045) and doctor-patient communication difficulty (P=0.034); the CAD-3DP group was also better than the 3DP group in the overall satisfaction (P=0.023), preoperative planning difficulty (P=0.046) and efficiency (P=0.014). Based on the subjective evaluations of patients and their families, the CAD-3DP group was better than the 3DP group in helping understand the vessel around the tumor (P=0.016), surgical procedure (P=0.020), procedure selection (P=0.029), and overall satisfaction (P=0.048); the CAD-3DP group was better than the 3DV group in helping understand the tumor size (P=0.038). Conclusion CAD-modified 3DP model has certain advantages in pre-planning, intraoperative navigation and doctor-patient communication in the VATS sublobectomy.
10.Treatment strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for gastric cancer with peritoneal metastasis: a systematic review
Chenghao JI ; Linpo ZHOU ; Yebin YANG ; Junqiang HU ; Haoran WEI ; Fanhe DONG ; Yuqiang SHAN ; Wencheng KONG
Chinese Journal of Gastrointestinal Surgery 2024;27(7):740-748
Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m 2 of Cisplatin and 30-40 mg/m 2 of Mitomycin C in 3-4 L saline solution at 42-43℃. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.


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