AIM To explore the effects of Buyang Huanwu Decoction on mitochondrial oxidative damage and PKCε-Nampt pathway in rats following cerebral ischemia reperfusion(I/R).METHODS The rats were randomly divided into the sham operation group,the model group,Buyang Huanwu Decoction group(14.3 g/kg)and edaravone group(3 mg/kg).Except those of the sham operation group,SD rats of other groups were induced into models of brain I/R injury by MCAO method,followed by corresponding drug administration 24 hours after operation.After 7 days of administration,the rats had their neurological deficit evaluated by neurological function scoring;thier expression of neuron marker MAP-2 detected by immunofluorescence staining;their neuron damage observed and the oxidative damage evaluated through assessment of their ROS levels and MDA and SOD activities;their changes of mitochondrial membrane potential detected by fluorescent probe JC-1;their ratio of NAD+/NADH detected using modified enzyme circulation method;their expressions of PKCε,p-PKCε and Nampt proteins detected with Western blot;and their positive expressions of p-PKCε and Nampt proteins detected with immunohistochemistry method.RESULTS Compared with the model group,Buyang Huanwu Decoction group shared decreased cerebral infarction volume and neurological function score(P<0.05);increased cerebral fluorescence intensity of MAP-2(P<0.05);reduced neuronal damage,decreased cerebral levels of ROS and MDA(P<0.05);increased SOD activity,mitochondrial membrane potential and NAD+/NADH ratio(P<0.05);and increased protein expressions of p-PKCε and Nampt(P<0.05).CONCLUSION Buyang Huanwu Decoction can improve mitochondrial function and reduce brain I/R injury in rats by activating their PKCε-Nampt signaling pathway.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To compare the feasibility and efficacy of translocator protein (TSPO) molecular probes N, N-diethyl-2-(2-(4- 18F-fluorophenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-FDPA) and 18F-(R)-( N-sec-butyl)-3-fluoromethyl- N-methyl-4-phenylquinoline-2-carboxamide (LW223) for the detection of abdominal vulnerable atherosclerotic plaques (VAP) in rabbit models. Methods:Nine healthy New Zealand white rabbits were divided into group A (control group, n=3), group B (VAP group, n=3) and group C (VAP treatment group, n=3) using completely randomized design. Animals were injected with 18F-FDPA and 18F-LW223 at the end of 12, 16 and 24 weeks. PET/CT and CT angiography (CTA) was performed 40-50 min post injection. All rabbits were sacrificed at the end of 24 weeks after imaging studies. All abdominal aortas were collected for pathological and immunofluorescence examination. Repeated measures analysis of variance (Bonferroni test) and paired t-test were used to analyze the data. Results:Target-to-background ratio (TBR; abdominal aortic lesion/left ventricular blood pool) values of 18F-FDPA in 3 groups at the end of 12, 16 and 24 weeks were significantly different ( F values: 68.09-144.88, all P<0.001). At the end of 12 weeks, there was no increased uptake of 18F-FDPA in the abdominal aorta region in 3 groups. The local 18F-FDPA uptake of the abdominal aorta in group B was significantly higher than the uptake in group C and that in group A at the end of 16 and 24 weeks( P<0.05 or P<0.001), and there were significant differences between group C and group A, with higher uptake in group C (both P<0.01). In 3 groups, there was no significant 18F-LW223 uptake in the abdominal aorta region at 3 time points of PET/CTA imaging. At the end of 12, 16 and 24 weeks, TBR values of 18F-FDPA and 18F-LW223 in 3 groups exhibited statistical differences ( t values: 2.88-36.79, all P<0.05). HE, immunofluorescent CD68 and TSPO staining showed more macrophage infiltration in group B than group C. Conclusion:18F-FDPA can be used to detect VAP in rabbits′ abdominal arteries at early time compared to 18F-LW223, and to evaluate the changes in the stability of vulnerable plaque after lipid-lowering drug intervention.

AIM To study the chemical constituents from salt-processed Citri Reticulatae Semen and their antioxidant activities.METHODS The 85% ethanol extract from salt-processed Citri Reticulatae Semen was isolated and purified by silica gel,D101 macroporous resins,MCI,ODS,Sephadex LH-20 and semi-prepative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their antioxidant activities in vitro of the ethanol extract of Citri Reticulatae Semen,salt-processed Citri Reticulatae Semen and all the obtained compounds were evaluated by DPPH and ABTS+assay.RESULTS Sixteen compounds were isolated and identified as limonin(1),obacunone(2),nomilin(3),deacetyl nomilin(4),kaempferol(5),nobiletin(6),diosmetin(7),isosakuranetin(8),hesperetin(9),epicatechin(10),trans-p-menthane-1α,2β,8-triol(11),byakangelicin(12),vanillin(13),p-coumaric acid(14),4-[(1-ethoxy-2-hydroxy)ethyl]phenol(15),catechol(16).Compound 10 showed strong DPPH free radical scavenging activity,with an IC50 value of(0.015±0.001)μmol/mL,and strong ABTS+radical scavenging activity,with an IC50 value of(0.010±0.005)μmol/mL.CONCLUSION Compounds 8,11,15-16 are isolated from genus Citrus for the first time,5,12,14 are obtained from Citri Reticulatae Semen for the first time.Compound 10 shows obvious antioxidant activities.After salt roasting,the antioxidant activity of the ethanol extract of Citri Reticulatae Semen is enhanced.

AIM To study the chemical constituents from the leaves of Citrus reticulata Blanco and their anti-inflammatory activities.METHODS The 85%ethanol extract from the leaves of C.reticulata was isolated and purified by silica gel,D101 macroporous resin,MCI,ODS and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The Griess method was used to determine their inhibitory activities on lipopolysaccharide-induced NO production in macrophages RAW 264.7 cells.The mice foot swelling inflammation model induced by carrageenan was established,and the levels of IL-1β,TNF-α were detected.RESULTS Twelve compounds were isolated and identified as nobiletin(1),tangeretin(2),5-demethylinoblitin(3),5,4'-dihydroxy-6,7,8,3'-tetramethoxy flavone(4),5-hydroxy-7,8,3',4'-trimethoxyflavanone(5),3,5,6,7,8,3',4'-heptamethoxyflavanone(6),hesperetin(7),5-hydroxy-6,7,3',4'-tetramethoxyphenone(8),β-balsam alcohol(9),stigmaster-5-en-3β-alcohol(10),p-hydroxybenzaldehyde(11),vanillin(12).Compounds 1,4,6,7,10 and 12 had strong inhibitory activites on NO release in LPS-induced RAW 264.7 cells,and the IC50 values were(25.21±2.10),(37.77±0.50),(38.19±1.58),(21.89±1.73),(43.81±1.18),(47.98±2.55),(41.23±1.11),(43.80±1.43)μmol/mL,respectively.Compounds 2-3 reduced IL-1β and TNF-α levels(P＜0.05,P＜0.01).CONCLUSION Compounds 6-7,9 are isolated from this plant for the first time.Compounds 1-4,8 exhibit strong in vitro anti-inflammatory activities,and compounds 2-3 exhibit significant in vivo anti-inflammatory activities.

[Abstract] Objective To study the role of hypoxia inducible factor-1α (HIF-1α) / stromal cell-derived factor-1 (SDF-1) pathway in high altitude hypoxia preconditioning in rat. Methods Seventy-six adult male SD rats, which through fed in low-pressure oxygen chamber (altitude 5000 m) and Xining (altitude 2260 m) to establish the rat model of hypoxia preconditioning. Rats randomly divided into 6 groups: control group (Ctrl), high altitude hypoxic preconditioning 1 day group (HHP-1d), high altitude hypoxic preconditioning 4 days group (HHP-4d), high altitude hypoxic preconditioning 15 days group (HHP-15d), high altitude hypoxic preconditioning 30 days group (HHP-30d), medium altitude hypoxic preconditioning group (MHP). 7. 0 T small animal MRI was used to observe the intracranial structure, diameter of basilar artery and cerebral blood flow in the hippocampus and brainstem regions by the sequences of T2 weighted images (T2WI) and arterial spin labeling (ASL) in the groups of Ctrl, HHP-4d, HHP-30d and MHP. In each group, blood routine was tested, the concentrations of HIF-1α, SDF-1 in serum, platelet activating factor (PAF)and P-selectin (SELP) in plasma were detected by the method of ELISA. Results In the hypoxia preconditioning groups, intracranial structure and diameter of basilar artery had no significant difference, while cerebral blood flow in the regions of brainstem and hippocampus increased significantly (P<0. 05). Meanwhile, red blood cell and white blood cell increased significantly, while platelet decreased significantly in the groups of hypoxia preconditioning (P<0. 05). Red blood cell and platelet in MHP group were closer to Ctrl group. The concentrations of HIF-1α and SDF-1 (except HHP-1d group) increased significantly in hypoxia preconditioning groups (P<0. 05).The concentrations of PAF and SELP increased significantly in HHP-1d and HHP-15d groups. The concentration of PAF decreased significantly in the HHP-4d and HHP-30d groups, and SELP decreased significantly in HHP-4d group (P<0. 05). Conclusion Hypoxia preconditioning can increase oxygen storage and immune defense capacity, improve brain reserve capacity and play the effect of brain protection through HIF-1α/ SDF-1 pathway. The best effect preconditioning was feed at medium altitude (altitude 2260 m) for 30 days.

Objective:To serially characterize the myocardial perfusion, myocardial hibernation and left ventricular (LV) function as well as LV remodeling in progressive coronary artery stenosis in Chinese mini-pigs.Methods:In 8 Chinese mini-pigs (5 males, 3 females; age: 10 months), chronic progression of coronary stenosis and finally occlusion was established using Ameroid constrictor implantation at the 1 cm below the bifurcation of the first diagonal branch of the left anterior descending (LAD) artery. Serial gated 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT, gated 18F-FDG PET/CT imaging and coronary angiography (CAG) were performed before surgery and at the 1st, 4th and 8th week after surgery. Longitudinally, total perfusion defect (TPD), LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), summed motion score (SMS), summed thickening score (STS) and hibernating myocardium (HM) were analyzed. Repeated measures analysis of variance, Kruskal-Wallis rank sum test and Bonferroni correction method were used to analyze data. Results:One mini-pig died of infection after the Ameroid constrictor implantation. In the remaining 7 mini-pigs, TPD was progressively increased with time prolonged (0, 12.0%(0, 33.0%), (41.1±23.7)% and (49.3±24.5)%; H=17.03, P=0.001); Compared with HM before the surgery (100%), HM was gradually reduced from the 1st (21.0%(6.0%, 100%)) to the 4th (18.0%(3.0%, 33.0%)) week after surgery, and then increased to the 8th week after surgery ((23.0±15.4)%; H=13.09, P=0.004), but there was no significant difference between the 1st and 4th week, or between the 4th and 8th week after surgery (both P>0.05 (Bonferroni correction method)). Accordingly, LVEF gradually decreased ((73.7±8.4)%, (63.7±19.1)%, (53.7±14.6)% and (49.9±15.4)%; F=6.22, P=0.004). LVEDV (9.0(6.0, 21.0), (31.4±16.3), (32.9±17.4) and (36.4±17.5) ml; H=8.58, P=0.035)and LVESV ((3.8±3.2), (15.9±15.3), 12.0(10.0, 17.0)and (19.3±10.9) ml; H=10.51, P=0.015) gradually increased. SMS and STS continuously increased as well ( H values: 16.49, 13.33, P values: 0.001, 0.004). Conclusions:With the progression of coronary artery stenosis to occlusion, myocardial perfusion is gradually decreased, while the global and regional LV function, LV remodeling are gradually aggravated, and HM is gradually reduced. After the chronic coronary artery occlusion, myocardial perfusion has a trend to be improved and HM is gradually recovered.

Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m²(range: 18.1 to 30.1 kg/m²). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ² test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.
Adolescent ; Adult ; Aged ; Child ; Duodenum/surgery* ; Female ; Humans ; Male ; Middle Aged ; Pancreas/surgery* ; Pancreatectomy ; Pancreatic Neoplasms/surgery* ; Pancreaticoduodenectomy ; Postoperative Complications ; Retrospective Studies ; Young Adult

Lysophosphatidic acid (LPA), a bioactive lipid medium, plays an important role in the development and progression of ovarian cancer. Doxorubicin hydrochloride (DOX) is a first-line drug in the ovarian cancer clinical therapy, while the effect and molecular mechanism of LPA in the ovarian cancer with DOX treatment is still unclear. This study intended to explore the effect and molecular mechanism of LPA in ovarian cancer treated with DOX. SKOV3 and OVCAR-3 cells of human ovarian cancer and Chinese hamster ovary cells were treated with control, LPA (lOp-mol/L), DOX (2jjLmol/L) and LPA (10jJLmol/L) + DOX (2p,mol/L) respectively for 24 hours. The morphological changes of SKOV3 cells were observed under optical microscope and transmission electron microscope. Results showed that LPA reduced cell death and the degree of chromatin aggregation in SKOV3 cells treated with DOX; RT-qPCR showed that LPA treatment could down-regulate the mRNA levels of caspase-3 in DOX-treated SKOV3 cells (P<0. 05); Western blot showed that LPA treatment could reduce caspase-3 and cleaved caspase-3 levels treated with DOX in SKOV3, OVCAR-3 and CHO cells (P<0. 05); Flow cytometry using Annexin V/PI double staining showed that LPA could down-regulate apoptosis in SKOV3 cells treated with DOX (P<0. 05); DCFH-DA method was used to detect intracellular levels of reactive oxygen species (ROS) in SKOV3 cells. It was found that LPA reduced the intracellular ROS level treated with DOX (P<0. 05). Our preliminarily study showed the effect of LPA in the apoptosis of ovarian cancer treated with DOX, which may provide a reference for the drug therapy of ovarian cancer targeting LPA.