OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

Objective To study the role of microRNA(miR)-483-3p in reducing myocardial fibrosis in rats,and explore the relationship between its mechanism and autophagy.Methods A total of 24 male SD rats were randomly divided into sham operation group,model group,blank transfec-tion group and high expression group,with 6 rats in each group.The blank transfection group and the high-expression group were pretreated with a single injection of adeno-associated virus(AAV)-blank transfection and AAV-miR-483-3p(5×1011 vg)in the tail vein,respectively.In 14 d later,the sham group was injected with 2.5 ml/(kg·d)normal saline for 14 d,and rat model of myocardial fibrosis was established by 2 mg/ml isoproterenol[2.5 ml/(kg·d)]injection through tail vein for 14 consecutive days.Myocardial pathological damage,severity of myocardial fibrosis,and expression levels of collagen-Ⅰ,microtubule-associated protein light chain 3(LC3),autoph-agy-related protein 5(Atg5)and autophagy degradation substrate(P62)in cardiomyocytes were evaluated and measured.Results Compared with the sham operation group,the model group had obviously larger myocardial fibrosis area,higher positive expression of Collagen-Ⅰ,and increased protein levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ,and decreased expression level of P62 protein(P＜0.05).The myocardial fibrosis area,positive expression of Collagen-Ⅰ,the expression levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ protein[(13.64±1.51)％vs(27.47±1.55)％,(13.48±3.07)％vs(30.91±2.45)％,0.98±0.17 vs 1.24±0.28,0.66±0.05 vs 1.26±0.09,P＜0.05]were significant-ly decreased,and the expression level of P62 was notably increased(0.91±0.11 vs 0.74±0.06,P＜0.05)in the high expression group than the model group.Conclusion MiR-483-3p attenuates myocardial fibrosis in rats,and the mechanism may be related to the inhibition of cardiomyocyte autophagy.

Objective To explore the therapeutic effect of bicyclol(BIC)on rat model of myocardial fibrosis and its possible mechanism.Methods Twenty-four SPF male SD rats were randomly di-vided into sham group,model group,low-and high-dose groups,with 6 rats in each group.Except for the sham group,all other groups were injected with 5 mg/(kg·d)isoproterenol by tail vein to establish myocardial fibrosis model,and the low-and high-dose groups were administered by ga-vage with 100 and 200 mg/(kg·d)BIC,respectively for 14 consecutive days.HE staining and Masson staining were used respectively to observe the severity of myocardial injury and fibrosis.Western blot assay was employed to detect the protein expression of Collagen Ⅰ,Collagen Ⅲ,al-pha smooth muscle actin(α-SMA),methyltransferase-like protein 3(METTL3),α-ketoglutarate-dependent dioxygenase AlkB homolog 5(ALKBH5)and YTH domain family protein 1(YTHDF1)in rat myocardium.Results Compared with the sham group,myocardial cell necrosis and myocardial fibrosis were significantly more serious in the model group.Low-and high-dose BIC treatment reduced myocardial cell rupture and necrosis and myocardial fibrosis when com-pared with the model group.The expression levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,METTL3 and YTHDF1(P＜0.05)were significantly higher,and that of ALKBH5(0.58±0.02 vs 0.88±0.07,P＜0.05)was notably lower in the myocardial tissues of the model group than the sham group.While,both doses of BIC treatment significantly reversed above changes in protein levels(P＜0.05).Conclusion BIC can effectively alleviate myocardial structural damage and interstitial collagen deposition in rats with isoproterenol-induced myocardial fibrosis,and its mechanism may be related to m6A methylation modification.

Humans ; Parkinson Disease/diagnosis* ; Machine Learning

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

Objective: To explore the value of ultrasound in the differential diagnosis of neonatal upper and lower gastrointestinal tract(GIT)perforation. Methods: We retrospectively reviewed the ultrasound findings of 42 neonates of surgery-confirmed neonatal GIT perforation in our hospital from January 1, 2015 to December 31, 2018.The accuracy of ultrasound for detecting GIT perforation and the ultrasound features of upper and lower GIT perforation were evaluated. Results: (1)Of the 42 neonates with GIT perforation, 1 case didn′t undergo ultrasound, 2 cases were missed, and 1 case was misdiagnosed.Thirty-eight neonates were diagnosed of GIT perforation by ultrasound preoperatively, with a detection rate of 92.7%(38/41). The locations of GIT perforation were identified by ultrasound in 30 cases(78.9%, 30/38), including 11 cases of upper GIT perforation and 19 cases of lower GIT perforation.(2)A common sonographic finding of GIT perforation in 38 cases was pneumoperitoneum, which appeared as an echogenic line with posterior reverberation artifact under diaphragm or anterior to hepatic/splenic surface and a "stratosphere" sign in M-mode sonography.Free gas changed position when the patient′s position was changed, and didn′t change due to respiratory change.Besides, free gas dispersed with compression on abdomen, and gathered without compression.(3)Upper GIT perforation was showed that poor filling of the stomach cavity, and the abdominal free gas sharply increased.Lower GIT perforation was characterized by collapsed bowel, blurred and interrupted intestinal wall structure, and more accompanied with intestinal obstruction.(4)There was no significant difference of detection rate between ultrasound and X-ray in diagnosing GIT perforation[92.7%(38/41)vs.83.3%(35/42)](P>0.05), whereas ultrasound more sensitive for a very small amount of free gas in the early stage of perforation.(5)Helicobacter pylori infection was found in two cases of GIT perforation. Conclusion Ultrasound can be used for differential diagnosis of upper and lower GIT perforation, and could be recommended as the first choice for detecting GIT perforation in neonatal patients.

Objective To assess the safety, feasibility and short?term outcome of totally laparoscopic distal gastrectomy(TLDG). Methods Seventy?five patients who underwent laparoscopic distal gastrectomy in Cancer Hospital of Chinese Academy of Medical Science between August 2015 and April 2018 were enrolled in this study. A total of 46 laparoscopy?assisted distal gastrectomy ( LADG) cases and 29 TLDG cases were included. The Short?term outcomes and safeties of the two groups were compared. Results The operation time of TLDG group was significantly longer than that of LADG group (207±41 vs. 156± 34 min, P＜0.001), while the length of wound was shorter in the TLDG group (3.6±0.6 vs. 5.8±0.8 cm, P＜0.001). The time to first flatus in TLDG group was (3.3±0.6) days, significantly shorter than (3.7±0.8) days in LADG group ( P＝0.034). There were no significant differences between the two groups in the estimated blood loss, intraoperative blood transfusion, extraction of gastric tube, drainage tube removal, interval of the first time to eat semi?liquid food, postoperative hospital stays, surgical complications, number of retrieved lymph nodes, proximal and distal resection margin lengths ( all P＞0.05). The white blood cell count at postoperative day 1 in the TLDG group was (10.96±1.96)×109／L, significantly lower than (12.49± 3.46)×109／L of the LADG group ( P＝0.017).While the CRP level at postoperative day 1 in the TLDG group were lower than that of LADG group, no statistical difference was observed (P＝0.072). Conclusions Our study shows that TLDG is safe and feasible. TLDG has better cosmesis, less blood loss, and faster recovery compared to LADG.

Objective To assess the safety, feasibility and short?term outcome of totally laparoscopic distal gastrectomy(TLDG). Methods Seventy?five patients who underwent laparoscopic distal gastrectomy in Cancer Hospital of Chinese Academy of Medical Science between August 2015 and April 2018 were enrolled in this study. A total of 46 laparoscopy?assisted distal gastrectomy ( LADG) cases and 29 TLDG cases were included. The Short?term outcomes and safeties of the two groups were compared. Results The operation time of TLDG group was significantly longer than that of LADG group (207±41 vs. 156± 34 min, P＜0.001), while the length of wound was shorter in the TLDG group (3.6±0.6 vs. 5.8±0.8 cm, P＜0.001). The time to first flatus in TLDG group was (3.3±0.6) days, significantly shorter than (3.7±0.8) days in LADG group ( P＝0.034). There were no significant differences between the two groups in the estimated blood loss, intraoperative blood transfusion, extraction of gastric tube, drainage tube removal, interval of the first time to eat semi?liquid food, postoperative hospital stays, surgical complications, number of retrieved lymph nodes, proximal and distal resection margin lengths ( all P＞0.05). The white blood cell count at postoperative day 1 in the TLDG group was (10.96±1.96)×109／L, significantly lower than (12.49± 3.46)×109／L of the LADG group ( P＝0.017).While the CRP level at postoperative day 1 in the TLDG group were lower than that of LADG group, no statistical difference was observed (P＝0.072). Conclusions Our study shows that TLDG is safe and feasible. TLDG has better cosmesis, less blood loss, and faster recovery compared to LADG.

Objective To evaluate early skeletal muscle myopathy with contrast‐enhanced ultrasound ( CEUS) in diabetic rabbits . Methods Alloxan ( 100 mg/kg ) was given intravenously to 11 New Zealand w hite rabbits . Another 5 age‐matched normal rabbits were used as controls .CEUS was performed at baseline and 1 ,2 ,3 months after the establishment of diabetes ,respectively . T hen ,skeletal muscle samples were obtained for pathological observation . Additionally ,the diabetic rabbits were divided into 3 groups according to their pathologic findings : mild , moderate , and severe myopathy group . M icro‐perfusion parameters ,including artery‐to‐vein transit time ( A‐VT T ) ,muscle tissue mean transit time ( M‐M T T ) and muscle tissue peak intensity ( M‐PI) were calculated . Results T he diabetic rabbits exhibited a lower body weight increase and a decrease of muscle thickness .Plasma levels of triglyceride ,cholesterol and creatinine were significantly higher in diabetic group than those in control group ( P ＜0 .05) . T he A‐V T T and M‐M T T values of the diabetic rabbits significantly increased over time ( all P ＜ 0 .05 ) ,whereas M‐PI value significantly decreased compared with that in control group ( P ＝ 0 .013 ) . Besides ,the A‐V T T value was significantly higher in severe myopathy group than that in mild group ( P ＝0 .001) . T he M‐M T T values in both moderate and severe groups were significantly higher w hen compared to that in mild group ( all P ＜0 .05) . T he A‐VT T and M‐M T T values were correlated with the severity of diabetic myopathy( e＝0 .898 , P ＜0 .001 ;e＝ 0 .527 , P ＝ 0 .01 ) . Conclusions Diabetic rabbits have defective skeletal muscle micro‐ perfusion in the early stage . CEUS can quantify impaire muscle microcirculation ,and is a valuable tool for assessment of diabetic myopathy .

Objective: To assess the safety, feasibility and short-term outcome of totally laparoscopic distal gastrectomy(TLDG). Methods: Seventy-five patients who underwent laparoscopic distal gastrectomy in Cancer Hospital of Chinese Academy of Medical Science between August 2015 and April 2018 were enrolled in this study. A total of 46 laparoscopy-assisted distal gastrectomy (LADG) cases and 29 TLDG cases were included. The Short-term outcomes and safeties of the two groups were compared. Results: The operation time of TLDG group was significantly longer than that of LADG group (207±41 vs. 156±34 min, P<0.001), while the length of wound was shorter in the TLDG group (3.6±0.6 vs. 5.8±0.8 cm, P<0.001). The time to first flatus in TLDG group was (3.3±0.6) days, significantly shorter than (3.7±0.8) days in LADG group (P=0.034). There were no significant differences between the two groups in the estimated blood loss, intraoperative blood transfusion, extraction of gastric tube, drainage tube removal, interval of the first time to eat semi-liquid food, postoperative hospital stays, surgical complications, number of retrieved lymph nodes, proximal and distal resection margin lengths (all P>0.05). The white blood cell count at postoperative day 1 in the TLDG group was (10.96±1.96) ×10⁹/L, significantly lower than (12.49±3.46)×10⁹/L of the LADG group (P=0.017). While the CRP level at postoperative day 1 in the TLDG group were lower than that of LADG group, no statistical difference was observed (P=0.072). Conclusions Our study shows that TLDG is safe and feasible. TLDG has better cosmesis, less blood loss, and faster recovery compared to LADG.