In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Diarrhea caused by chemotherapy is called chemotherapy-related diarrhea （CRD）. CRD can lead to reduced treatment effectiveness and compliance， affect the long-term outcome of tumor patients， and can be life-threatening in severe cases. In addition to conventional chemotherapy drugs， many molecularly targeted drugs are also associated with CRD， including small molecule epidermal growth factor receptor （EGFR） inhibitors， anti-EGFR monoclonal antibodies， phosphoinositide 3-kinase inhibitors， small molecule inhibitors of vascular endothelial growth factor receptor， BCR-ABL1 and KIT inhibitors， human epidermal growth factor receptor 2 target inhibitors， cyclin-dependent protein kinase inhibitors， antibody-drug conjugates and other molecularly targeted drugs. The occurrence mechanism may be related to the intestinal mucosal injury or enteritis caused by molecularly targeted drugs. The clinical manifestations are increased stool frequency and/or loose imposition， and patients are often associated with excess hyperproduction and/or colic. The incidence of CRD varies with different drugs. Great importance should be attached to collecting medical history and differential diagnosis， actively intervening and conducting dynamic evaluation， strengthening patient education， and timely detecting and preventing the occurrence of intestinal toxicity.

BACKGROUND:Traditional scoliosis orthosis has some disadvantages,such as complex manufacturing process,long processing cycle,poor fit and so on.Three-dimensional printed scoliosis orthosis has the advantages of high manufacturing precision and personalization. OBJECTIVE:To evaluate the efficacy of three-dimensional printed scoliosis orthosis for scoliosis based on multi-criteria decision model. METHODS:Clinical data of 72 patients with scoliosis admitted to Chen Xinghai Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to October 2022 were retrospectively collected and divided into two groups according to the treatment of orthosis.Study group(n=23)received three-dimensional printed scoliosis orthosis.Traditional group(n=49)received the traditional polypropylene spine brace treatment.The clinical efficacy and complications were compared between the two groups.A multi-criteria decision model for the treatment of scoliosis with three-dimensional printed scoliosis orthosis was established,and the stability of the benefit value,risk value and decision model of the two groups were evaluated. RESULTS AND CONCLUSION:(1)Compared with the traditional group,there were significant differences in the top vertebral offset distance,Cobb angle,top vertebral rotation,Functional Movement Screen score,visual analog scale score and total effective rate in the study group at 6 months after surgery(P<0.05).(2)Among the benefit indexes,Cobb angle had the greatest impact on the condition of patients,while the risk indexes had the greatest impact on dyspnea.(3)The benefit values of the study group and the traditional group for scoliosis were 79 and 64,and the risk values were 74 and 57,respectively.The combined benefit and risk values found that the benefit-risk value of the study group was 16 higher than that of the traditional group.(4)In the range of 0-100%relative risk weight,the benefit-risk value of the study group was always higher than that of the traditional group,which proved that the multi-criteria decision-making model had good stability.(5)It is indicated that three-dimensional printed scoliosis orthosis can better restore the physiological curvature of scoliosis and improve the efficiency of treatment.

Sepsis is a syndrome of systemic inflammatory response in which the body′s response to infection is dysregulated, and is characterized by persistent infection, excessive inflammation and immunosuppression, etc. It often leads to organ dysfunction and can be life threatening, and also a common complication after trauma. The pathogenesis of post-traumatic sepsis is still unclear at present due to the complexity of its etiology, progression and prognosis. Multi-omics technology is a method to combine two or more single omics for comprehensive analysis, which can reveal the interaction network among the disease-associated molecules from multiple perspectives and aspects and is of great significance for the analysis of the pathogenesis of post-traumatic sepsis. To this end, the authors reviewed the research progress on the role of multi-omics technology in elucidating the pathogenesis of post-traumatic sepsis from the perspectives of genomics, transcriptomics, proteomics, metabolomics, single-cell transcriptomics and combination of multi-omics technologies, etc so as to provide a reference for the researches on post-traumatic sepsis.

Objective:To observe the clinical efficacy of exercise-based acupuncture in treating ischemic stroke and its effects in improving the patient's motor function and daily living ability. Methods:A total of 106 patients with motor dysfunction due to cerebral infarction were randomized into a trial group and a control group,each consisting of 53 cases.Both groups received conventional rehabilitation;in addition,the control group was given point-toward-point acupuncture at scalp points,and the trial group was offered exercise-based acupuncture,3 times weekly for 4 consecutive weeks.Before treatment,after 2 and 4 weeks of treatment,and at the 2-month follow-up,the Fugl-Meyer assessment(FMA)scale,Lovett scale for muscle strength,modified Ashworth scale(MAS),and activities of daily living(ADL)scale were used to assess the patient's motor function,muscle strength,muscle tension,and daily living ability. Results:After treatment,both groups gained improvements in motor function and daily living ability;after 4-week treatment and at the 2-month follow-up,the trial group had higher FMA and ADL scores than the control group(P<0.05).The MAS score decreased after treatment in both groups;after 2 and 4 weeks of treatment and at the 2-month follow-up,the MAS score was lower in the trial group than in the control group(P<0.05).After the intervention,the Lovett score increased in both groups;after 4 weeks of treatment,the Lovett score was higher in the trial group than in the control group(P<0.05). Conclusion:Based on routine rehabilitation,exercise-based acupuncture and scalp point-toward-point acupuncture both can improve the motor function and daily living ability in ischemic stroke patients;exercise-based acupuncture performs better than scalp point-toward-point acupuncture.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

OBJECTIVE：To compare the eff icacy and safety of rivaroxaban versus enoxaparin in the treatment of malignant tumor complicated with venous thromboembolism （VTE），and to provide evidence-based reference to the clinic. METHODS ： Retrieved from PubMed ，Embase，Cochrane Library ，Clinical Trials ，CNKI，CBM and VIP ，clinical trials or observational studies about rivaroxaban versus enoxaparin were collected during the inception to Apr. 2020. After literature screening and data extraction ， the quality of included literatures were evaluated by Newcastle Ottawa scale ；Stata 15.0 software was used to conduct Meta-analysis，sensitivity analysis and publication bias analysis. RESULTS ：A total of 5 observational clinical cohort studies were retrieved，including 4 retrospective cohort studies and one prospective cohort study. Totally 997 patients were included ，among which 625 patients received enoxaparin and 372 patients received rivaroxaban. Results of Meta-analysis showed that there was no statistical significance in recurrence rate of VTE at 3 months follow-up [RR ＝0.91，95％CI（0.50，1.66），P＝0.760] and 6 months follow-up [RR ＝0.53，95％CI（0.24，1.15），P＝0.106] as well as the incidence of massive hemorrhage at 3 months follow-up [RR ＝ 1.22 ，95％CI（0.66，2.25），P＝0.530] and 6 months follow-up [RR ＝1.30，95％CI（0.73，2.33），P＝0.368]. The results of sensitivity analysis showed that the results of above Meta-analysis were stable ；the results of publication bias analysis showed that there was less possibility of publication bias in this study. CONCLUSIONS ：Rivaroxaban is as effective and safe as enoxaparin in the treatment of malignant tumor with VTE.

Clinical data of 4 cases of infants with hemophilia complicated with hematorrhachis diagnosed in Guangzhou Women and Children′s Medical Center from January 2017 to December 2018 was retrospectively analyzed.The clinical manifestations of 4 children was atypical, only showing irritability and crying, poor spirit and weak head in the early stage, and torticollis and limb weakness in the late stage may easily contribute to a misdiagnosis.The spinal magnetic resonance imaging is an important diagnosis of hematorrhachis.The most common site of disease was cervicothoracic and thoracolumbar spinal epidural hemorrhage.Of the 4 patients in this article, 1 patient was treated with surgery combined with infusion factor Ⅷ replacement therapy.Three patients were treated with infusion factor Ⅷ replacement therapy alone to obtain clinical rehabilitation.The prognosis of early diagnosis was good, the time from onset to diagnosis in 3 cases was within 1 week, after treatment all had rehabilitation; 1 case within 2 weeks of diagnosis, partial rehabilitation.It is suggested that hemophilia complicated with hematorrhachis in infants is hidden, and it can only be irritable and crying in the early stage, and neurological symptoms appear in the late stage.Improving diagnostic awareness, early diagnosis and early infusion factor replacement therapy are critical for prognosis.

Objective To evaluate the left ventricular systolic function of patients with type 2 diabetes combined with microangiopathy using two dimensional speckle tracking imaging. Methods A total of 29 simple diabetes patients from January 2016 to December in Zhejiang Chinese Medicine University Affiliated Jiaxing Hospital of Traditional Chinese Medicine (DM group), 35 diabetes patients with microvascular disease (diabetic microangiopathy group), and 35 healthy volunteers (healthy control group) were enrolled in present study. The conventional echocardiography was used to evaluated the left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVEDS), end diastolic ventricular septal thickness (IVSDD), left ventricular posterior wall end diastolic thickness (LVPWTD), left ventricular ejection fraction (LVEF), and left atrial volume index (LAVI). Using pulsed Doppler technique, the mitral early diastolic and late diastolic blood flow velocity ratio (E/A), E peak deceleration time (DCT), the organization of the mitral E wave velocity and the Doppler organization Doppler e' ratio (E/e) were measured. Automatic functional imaging was used to calculate the left ventricular apical axis, the four cavities of the apex, the two cavities of the apex and the overall mean longitudinal strain of the left ventricle. The clinical data, routine echocardiographic parameters and strain parameters among 3 groups were compared by one-way ANOVA. The Tukey HSD method was used to compare the differences between two groups. Pearson correlation analysis was used to analyze the correlation between the total mean longitudinal strain of left ventricle and the concentration of glycosylated hemoglobin, triglyceride concentration and systolic pressure. Results Among the 3 groups, the subject age, heart rate, body mass index had no significant difference. In diabetic microangiopathy group, the glycosylated hemoglobin concentration, triglyceride, systolic blood pressure were higher than that in healthy control and diabetic groups, and the differences were statistically significant (t=16.135, 8.947; t=8.777, 10.947; t=13.806, 8.278, all P＜0.05). The 3 groups had no significant differences in LVEDD, LVEDS, IVSDD, LVPWTD, DCT and LVEF. Compared with healthy controls, patients with diabetes mellitus showed decreased E/A and increased E/e; while patients with diabetic microangiopathy had decreased E/A and increased LAVI and E/e (t=13.786, 13.565; t=9.571, 11.267, 8.351, all P＜0.05). In the left ventricular apical long axis view, four chamber view, two chamber view and left ventricular overall average longitudinal strain values, increasing trend was found from healthy control group, to DM group, and to diabetic microangiopathy group, and the differences between any 2 groups were statistically significant (t=5.491, 10.907, 6.076; t=4.276, 7.011, 3.250; t=10.445, 11.633, 3.683; t=10.746, 18.731, 9.532; all P＜0.05). Pearson correlation analysis showed that the mean longitudinal strain value of left ventricle was negatively correlated with glycosylated hemoglobin concentration (r=-0.746, P=0.000), and there was no correlation with the triglyceride concentration and systolic blood pressure (r=0.079, P=0.438; r=0.067, P=0.416). Conclusion The two-dimensional speckle tracking imaging technique can effectively evaluate the left ventricular systolic function in patients with type 2 diabetic microangiopathy.