Objective:To investigate the effect of goal-directed fluid therapy(GDFT)under the guidance of LIDCOrapid hemodynamic monitor on postoperative nausea and vomiting(PONV)of patients after gynecological laparoscopic surgery.Methods:A total of 90 patients who underwent laparoscopic extensive hysterectomy under general anesthesia in Affiliated Hospital of Shandong Second Medical University from August 2020 to June 2021 were selected,and they were divided into observation group and control group as random number table,with 45 cases in each group.Patients in control group supplemented fluid according to the guidance of urine output and mean arterial pressure(MAP).Patients in observation group supplemented fluid according to GDFT under guidance of stroke volume variation(SVV).The MAP values,heart rates(HR),SVV values and cardiac index(CI)values at the 10th min after patients entered the operation room(T0),the 3rd min after anesthesia induction(T1),and the 3rd min(T2),the 30th min(T3)and the 1st h(T4)after Terndelenburg position,and the time of completing surgery(T5)were observed.In addition,the intraoperative intake and output volume of liquid,the indicators of gastrointestinal function recovery after surgery,and the length of stay also were observed.The PONV incidence of main outcome indicators,and the PONV scores of postoperative 0-6h(T6),6-12 h(T7),12-24 h(T8)and 24-48 h(T9)of secondary outcome indicators,as well as the number of patients who received the treatment of antiemetic compensation after surgery,were analyzed.Results:The PONV incidence of observation group was significantly lower than that of control group(x2=6.40,P<0.05).The PONV scores of postoperative T6 and T7 of observation group were significantly lower than those of control group(t=4.92,3.42,P<0.05),respectively.The HR and CI value at T4 of observation group were significantly higher than those of control group(t=0.73,0.64,P<0.05),while the SVV of observation group increased from T3 to T5,with significant differences(t=2.28,3.42,4.10,P<0.05),respectively.The intraoperative crystalline fluid input and total infusion volume decreased,while colloidal fluid input increased,and the differences of them between two groups were significant(t=15.10,12.36,8.19,P<0.05),respectively.The postoperative exhaust time,defecation time and feeding time of observation group were significantly earlier than these of control group(t=3.79,2.09,2.54,P<0.05),respectively.But there was no statistical difference in the length of stay between the two groups.Conclusion:GDFT,which is guided by LIDCOrapid hemodynamic monitor,may decrease the incidence of PONV of gynecological laparoscopic surgery and the severity of PONV within 12 hours after surgery.

This paper summarized the clinical experience of Professor LIU Shenlin in diagnosing and treating gastric cancer with the thinking of "prescription according to tendency". In this paper， the thinking of diagnosis and treatment for gastric cancer and medication skills were summarized into four dimensions： power， energy， chronology and situation. The diagnosis emphasizes the tendency of qi power， considering that the onset of gastric cancer primarily stems from the disorder of qi movement in zang-fu organs， and emphasizing the importance of regulating the liver and spleen qi to intercept the tendency of disease. It points out that dampness-phlegm-stasis-toxin is a crucial link leading to the metabolic imbalance of body energy， and Professor LIU adepts at using methods such as breaking up blood and expelling stasis， and clearing heat and resolving toxins to block the pathological chain reaction caused by energy imbalance and to restore the homeostasis of the organism. In the treatment process， according to the characteristics of gastric cancer staging and chronological evolution， we will explore the changes of the exuberance and weakness of healthy qi and pathogenic qi in the context of the chronologic tendency， and adjust the dosage of attacking and tonic medicines in different stages of the disease in order to balance and restore the body. The "situation" is in line with the state of consumptive disease in advanced gastric cancer， Professor LIU skillfully uses large doses of Huangqi （Astragalus mongholicus） with flexible combination of medicinals to replenish deficiencies， invigorate qi， and regulate blood vessels.

OBJECTIVE To investigate the effect of Jianpi Yangzheng(JPYZ)formula regulating tumor-associated macrophage(TAM)exosomes on anoikis in gastric cancer and its mechanism.METHODS TAM model was established by inducing human mononuclear THP-1 cells in vitro;M0,TAM and TAM+JPYZ formula exosomes were extracted by ultracentrifugation and co-incuba-ted with gastric cancer cells.Flow cytometry was used to detect the effect of exosomes in each group on anoikis in gastric cancer cells.A BALB/c transplanted tumor mouse model was constructed,and the expression level of apoptotic proteins in transplanted tumors was detected by Western blot.Label-free mass spectrometry proteomics and bioinformatics were used to analyze the differential proteins in gastric cancer cells before and after intervention;Western blot and qPCR experiments were used to detect the expression level of dif-ferential protein isocitrate dehydrogenase 1(IDH1),and ubiquitination experiments were used to detect the ubiquitination level of IDH1;kits were used to detect the levels of α-ketoglutarate(α-KG),NADPH/NADP+,glutathione(GSH/GSSG)and reactive oxy-gen species(ROS)content.RESULTS The anoikis rate of gastric cancer cells was reduced after TAM exosomes intervention(P<0.05,P<0.01),while it was significantly increased after TAM+JPYZ exosomes intervention(P<0.05,P<0.01).In the in vivo mouse experiment,the ratio of Cleaved Caspase-3/Caspase-3 in the tumor of the TAM exosome group was reduced(P<0.05),while the ra-tio was significantly increased after TAM+JPYZ exosome intervention(P<0.05).Proteomic analysis showed that IDH1 was significant-ly different after intervention,and was related to tricarboxylic acid cycle metabolism.Compared with the M0 group,the IDH1 ubiquiti-nation level of gastric cancer cells in the TAM group with exosome intervention was increased,the levels of α-KG,NADPH/NADP+and GSH/GSSG were significantly increased,and the ROS content was reduced(P<0.05),while TAM+JPYZ exosomes could reverse the above phenomenon.CONCLUSION JPYZ Formula can regulate TAM exosomes to cause ubiquitin degradation of IDH1 in gas-tric cancer cells,reduce the level of tricarboxylic acid cycle metabolism in gastric cancer cells,promote ROS accumulation,induce anoikis in gastric cancer,and thus inhibit the development of gastric cancer.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

【Objective】 To investigate the improvement of motor function recovery and the activation of endogenous neural stem cells (eNSCs) via voluntary exercise in mice with hyperlipidemia after intracerebral hemorrhage (ICH). 【Methods】 Four-month-old male Nestin-CreERT2: tdTomato transgenic mice were fed with high-fat diet (HFD) for eight weeks. Type Ⅳ collagenase was micro-injected into the corpus striatum to construct mouse ICH model with the help of stereotaxic apparatus. Voluntary exercise (wheel running) was initiated on the second day after ICH and monitored daily for seven days. Neurological severity score (NSS) and beam walking test were applied to evaluate motor function and coordination. Liver and brain tissues were collected at day 9 after ICH and sliced for staining. Then the Nestin-labeled cells, Ki67⁺, and doublecortin (DCX)⁺ in subventricular zone (SVZ) were counted to evaluate eNSCs activation. 【Results】 ① Compared with those of mice fed by chow diet (CD), the body weight, blood glucose level, concentration of lipid metabolism factors and the number of Nile Red positive cells in liver tissue were significantly higher in HFD-fed mice, confirming hyperlipidemia. ② Compared with the sham group, NSS score increased and the distance of cross-beam walking of ICH mice significantly decreased, showing the deficiency of motor function. It could be rescued by 7-day wheel running, as shown by a lower NSS score and a longer cross-beam walking distance. ③ Compared with the sham group, the number of Nestin⁺/Ki67⁺ cells decreased and Nestin⁺/DCX⁺ cells increased after ICH. After 7-day voluntary exercise, the number of Nestin⁺/Ki67⁺ cells decreased but that of Nestin⁺/DCX⁺ cells further increased significantly. However, compared with ICH, the increase of Nestin⁺/DCX⁺ cells in ICH+Ex was not significant. 【Conclusion】 Short-term voluntary exercise during the acute stage of ICH improved the recovery of motor function and enhance the proliferation of eNSCs in mice with hyperlipidemia. This provides a new idea for further developing ICH accelerated rehabilitation strategy based on eNSCs.

Organoids are three-dimensional structures formed by self-organizing growth of cells in vitro, which own many structures and functions similar with those of corresponding in vivo organs. Although the organoid culture technologies are rapidly developed and the original cells are abundant, the organoid cultured by current technologies are rather different with the real organs, which limits their application. The major challenges of organoid cultures are the immature tissue structure and restricted growth, both of which are caused by poor functional vasculature. Therefore, how to develop the vascularization of organoids has become an urgent problem. We presently reviewed the progresses on the original cells of organoids and the current methods to develop organoids vascularization, which provide clues to solve the above-mentioned problems.
Humans ; Organoids ; Neovascularization, Pathologic ; Technology

Objective:To study the efficacy and safety of EndoClot polysaccharide hemostatic system (EndoClot PHS) for heparinized arterial hemorrhage of upper digestive tract (Forrest Ⅰa) in animal model.Methods:Twelve experimental pigs were randomly divided into the test group ( n=6) and the control group ( n=6) by simple random grouping method. Gastric arterial hemorrhage models were established. Endoclot PHS and Hemospray were used to spray on the wound to stop bleeding in the test group and the control group respectively. The time of effective hemostasis, the amount of hemostatic particles used, and the blockage of the powder feeding tube and its replacement were compared between the two groups. The survival and complications of experimental pigs were observed after the operation. In 10 days after the operation, the experimental pigs were euthanized for pathological dissection. Results:Spurting or pulsatile bleeding was achieved in all experimental pigs. There were significant differences in the time of effective hemostasis (8.75±0.84 min VS 9.83±0.62 min, t=-2.53, P=0.030) and the amount of hemostatic particles used to achieve effective hemostasis (6.71±0.39 g VS 14.10±1.62 g, t=-10.86, P<0.001) between the test group and the control group. There was no significant difference in the occurence of clogging or the replacement of powder feeding pipes between the two groups (0.64±0.02 times VS 0.67±0.04 times, t=-1.64, P=0.131). In addition, the gas source of the test group was stable, and the visual field under the endoscope was clear. Neither the test group nor the control group had gastric lesions, perforation, or embolism. The blood glucose, blood routine, and liver and kidney functions were normal, and no thrombosis or embolism of the main organs occurred in either group. Conclusion:EndoClot PHS is safe and effective for heparinized upper gastrointestinal arterial hemorrhage (Forrest Ⅰa) in animal models.

Objective:To evaluate the feasibility and effectiveness of sentinel lymph node (SLN) detection in the ovarian neoplasms.Methods:A search of the literature describing ovarian SLN was performed using China National Knowledge Infrastructure (CNKI), WANFANG DATA, VIP, PubMed, Embase, web of science, Cochrane library from 2000.01.01 to 2020.07.29. The quality evaluation and data extraction of the included literature were conducted, and the development rate, sensitivity and negative predictive value of SLN were calculated.Results:Eight prospective single-arm studies were included, with heterogeneity I2=57.41%>50%, and the P<0.1. A total of 96 patients with ovarian cancer [Stage International Federation of Gynecology and Obstetrics (FIGO)Ⅰ-Ⅱ] were included, of whom 93 completed systematic pelvic and para-aortic lymphadenectomy after SLN detection. The most common tracers were technetium-99m radioactive colloid ( 99Tc m), blue dye or indocyanine green (ICG), and the most common injection sites were the infundibulopelvic ligaments and the proper ovarian ligaments. The SLN detection rate was 88.5%(85/96) and the average number was 2-3. SLN was found in the ipsilateral or contralateral regions of the tumor, 40.8%(31/76) was found only in the para-aortic, 14.5%(11/76) was found only in the pelvic, and 44.7%(34/76) was found only in the para-aortic and pelvic region. The sensitivity was 90.9%(10/11) and the negative predictive value was 98.8%(82/83) of lymph node metastasis. Conclusions:SLN detection for ovarian neoplasms is feasible, and whether it can effectively predict lymph node status of ovarian cancer still needs large sample, multi-center, prospective clinical studies to further verify.

Objective:To study preoperative MRI imaging and its enhanced mode on tumor features in predicting microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).Methods:The clinical data of patients with a solitary HCC who underwent MRI examination followed by surgical resection at the General Hospital of Ningxia Medical University from January 2017 to June 2019 were studied. The patients were divided into the MVI (+ ) and MVI (-) groups according to the findings on postoperative pathological diagnosis. The relationship between the rates of MVI and MRI tumor features including diffusion weighted imaging (DWI) signal, enhancement mode, enhancement type and other imaging characteristics were analysed.Results:Of 84 patients with HCC enrolled into this study, there were 65 males and 19 females. Their age (Mean±SD) was (54.94±11.51) years. MVI (+ ) was found in 46 patients and MVI (-) in 38 patients. The maximum tumor diameters (Mean±SD) of the two groups were (7.08±3.45) cm and (4.28±2.47) cm ( P<0.01). Single-factor analysis and comparison of imaging characteristics of the two groups of patients showed tumor DWI signal, tumor encapsulation, enhancement mode, tumor edge smoothness, abnormal enhancement around tumors, and intratumoral arteries were significantly different ( P<0.05); There were no significant differences in T 1WI signals, T 2WI signals, tumor periphery, and enhancement types between groups. After inputting MVI(+ ) as a risk factor into the logistic regression model, tumor maximum diameters >6.33 cm, type 3/4 enhancement mode, and unsmoothness of tumor edge were independent risk factors (all P<0.05). Through combined diagnosis using ROC curve analysis with a cut-off value of 0.53, the area under the curve was 0.881, the sensitivity 0.870, specificity 0.789, and the Youden index 0.659. Conclusion:The multivariate logistic regression model and combined diagnosis using ROC curve analysis improved the diagnostic efficacy of MVI in its prediction of HCC on imaging studies. The risk predictors were easy to use and to promote in clinical practice.