AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

Objective:Studies have linked lack of sleep to oxidative stress,which can lead to learning and memory impairments.The melatonin derivative agomelatine(AGO)has antioxidant and neuroprotective effects.This study explored whether AGO can overcome oxidative stress and prevent cognitive dysfunction caused by sleep deprivation.Methods:Rapid eye movement sleep deprivation(REM-SD)model was prepared by multi-platform model induction.AGO was administered to REM-SD rats intragastrically.The spatial learning and memory ability of rats was detected by a novel object recognition test(NOR).The content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in hippocampal tissue of rats were detected by commercial kits.Results:REM-SD severely impaired the ability of rats to recognize novel objects(P＜0.05),and AGO treatment prevented this effect.In addition,MDA increased in hippocampus induced by REM-SD,while SOD activity decreased(P＜0.05).Conclusion:REM-SD causes cognitive dysfunction in rats,and AGO treatment may prevent this impairment by normalizing the antioxidant stress mechanism in the hippocampus.

Objective To explore the mechanism of Wenyang Shengji Ointment(温阳生肌膏,WYSJO)in the treatment of diabetic wounds from the perspective of network pharmacology,and to veri-fy it by animal experiments. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and related literature were used to screen active compounds in WYSJO and their corresponding targets.GeneCards,Online Mendelian Inheritance in Man(OMIM),DrugBank,PharmGkb,and Therapeutic Target Database(TTD)databases were employed to identify the targets associated with diabetic wounds.Cytoscape 3.9.0 was used to map the ac-tive ingredients in WYSJO,which was the diabetic wound target network.Search Tool for the Retrieval of Interaction Gene/Proteins(STRING)platform was utilized to construct protein-protein interaction(PPI)network.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were performed to identify signaling pathways be-tween WYSJO and diabetic wounds.AutoDock 1.5.6 was used for molecular docking of core components in WYSJO to their targets.Eighteen rats were randomly divided into control,model,and WYSJO groups(n=6).The model and WYSJO groups were used to prepare the model of refractory wounds in diabetes rats.The wound healing was observed on day 0,5,9,and 14 after treatment,and the wound tissue morphology was observed by hematoxylin-eosin(HE)staining.The expression levels of core genes were detected by quantitative real-time polymerase chain reaction(qPCR). Results A total of 76 active compounds in WYSJO,206 WYSJO drug targets,3 797 diabetic wound targets,and 167 diabetic wound associated WYSJO targets were screened out through network pharmacology.With the use of WYSJO-diabetic wound target network,core targets of seven active compounds encompassing quercetin,daidzein,kaempferol,rhamnetin,rham-nocitrin,strictosamide,and diisobutyl phthalate(DIBP)in WYSJO were found.GO enrich-ment analysis showed that the treatment of diabetes wounds with WYSJO may involve lipopolysaccharide,bacteria-derived molecules,metal ions,foreign stimuli,chemical stress,nutrient level,hypoxia,and oxidative stress in the biological processes.KEGG enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve advanced glycation end products(AGE-RAGE),p53,interleukin(IL)-17,tumor necrosis factor(TNF),hypoxia inducible factor-1(HIF-1),apoptosis,lipid,atherosclerosis,etc.The results of animal experiments showed that WYSJO could significantly accelerate the healing process of diabetic wounds(P<0.05),alleviate inflammatory response,promote the growth of granulation tis-sues,and down-regulate the expression levels of eight core genes[histone crotonyltrans-ferase p300(EP300),protoc gene-oncogene c-Jun(JUN),myelocytomatosis(MYC),hypoxia inducible factor 1A(HIF1A),mitogen-activated protein kinase 14(MAPK14),specificity pro-tein 1(SP1),tumor protein p53(TP53),and estrogen receptor 1(ESR1)]predicted by the net-work pharmacology(P<0.05). Conclusion The mechanism of WYSJO in treating diabetes wounds may be closely related to AGE-RAGE,p53,HIF-1,and other pathways.This study can provide new ideas for the phar-macological research of WYSJO,and provide a basis for its further transformation and appli-cation.

Objective:To analyze the causes of postoperative stricture of biliary-enteric anastomotic for congenital choledochal cysts.Methods:These 28 patients underwent salvage operation on an average 15 years (0.2-25 years) after initial surgeries at the Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital from Jan 2014 to Jun 2018.Results:In 26 patients the biliary-enteric anastomotic stenosis was benign, and in 2 the stricture was caused by cancerration. In 26 cases the Roux-en-Y hepaticojejunostomy was redone,among them 8 cases underwent concurrent hepatectomy for a better exposure of the intrahepatic bile duct. In 2 cases the anastomotic stenosis was found to be caused by canceration with extensive intraabdominal metastasis ,an external drainage was adopted. There were no inhospital deaths, and no serious complications. The postoperative follow-up time was 6-67 months. Two cancerated patients died within half a year, and the remaining patients had no long-term complications.Conclusions:Biliary-enteric anastomotic stenosis is one of the serious complications in postoperative patients for congenital choledochal cysts. Hence a wide, tension free biliary-enteric anastomosis performed by a experienced hand is necessary.

Objective:To evaluate partial ventral hepatectomy in the treatment of patients with complicated iatrogenic high bile duct injury.Methods:The clinical data of 8 cases of complicated iatrogenic high bile duct injury treated with the assistance of hepatic ventral segmentectomy from Mar 2013 to May 2020 at Hunan Provincial People's Hospital was retrospectively analyzed.Results:Among the 8 patients, 5 patients underwent partial Ⅳb lobectomy, and 3 patients received partial Ⅳb and Ⅴ segmentectomy of the liver. All the operation was successful without death in hospital. One case developed subphrenic infection and seroperitoneum, which was healed by anti-infection treatment and abdominocentesis. The postoperative follow-up time was 5-90 months, and all of patients are doing well. There was no stenosis in intrahepatic bile duct by postoperative cholangiography or MRI.Conclusions:Quadrate lobe hepatectomy provides a wide view for the treatment of complicated iatrogenic high bile duct injury by fully opening the first porta hepatis and exposing the primary and secondary bile duct branch helping establish a wide patent tension free bile duct-jejunostomy.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective To observe the effect of a high temperature environment on IL-17 concentration , neutrophil and lymphocyte in peripheral blood of soldiers on a training task .Methods Totally 160 health training soldiers were randomly and equally divided into two groups .The test group was trained and exposed to an environment of ( 32 ±1 )℃ vs control group at ( 22 ±1 )℃ for 2 hours before the IL-17 levels in venous blood were measured and peripheral neutrophils and lymphocytes were determined.Results The body temperatures were (38.74 ±0.26),(39.23 ±0.24),and (39.51 ± 0.34)℃after training for 40 min,50 min,and 60 min under a high temperature environment , respectively, and there was a significant increase of body temperature compared to the soldiers trained under normal conditions (P <0.05).Their perceived exertion rating was 17.62 ±0.66, 18.03 ±0.56, and 18.47 ±0.84, respectively, much unlike the control group (P<0.05).After 2 hours of training under high temperature , the concentration of IL-17 was (7.12 ±4.03) pg/ml, while the number of neutrophils and lymphocytes was (6.43 ±1.27) ×109/L and (9.84 ±1.36) ×109/L, respectively in peripheral blood, significantly higher than in the control group (P <0.05).Conclusion The body temperature and rating of perceived exertion of the training soldiers are significantly elevated under a high temperature environment, and the concentration of IL-17, and the neutrophils and lymphocytes counts in peripheral blood are increased .

Objective To investigate the effects of the low-osmolar nonionic contrast media on renal function in elderly patients suffering from ischemic cerebral vascular disease and undergoing angiography.To study the incidence and risk factors for contrast-induced nephropathy (CIN).Methods 276 elderly patients who were going to receive selective cranial angiography and bilateral renal angiography were included.The 0.9 ％ sodium chloride (1 ml · kg-1 · h-1) was administered in all patients 6 hours before and 12 hours after contrast media administration.No patients suffered from obviously congestive heart failure.The levels of serum creatinine (Scr) and serum urea nitrogen (SUN) were measured 3 days before and at day 1,2,6 after the administration of contrast media respectively.Then creatinine clearance rate (Ccr) was calculated.Multivariate predictors of contrastinduced nephropathy were determined by logistic regression.Results Among the 276 patients,CIN occurred in 19 patients (6.9％),among whom 4 patients suffered from severe renal artery stenosis and received percutaneous transluminal renal angioplasty (PTRA) at 1 week after undergoing angiography.The renal function in the other 15 cases with CIN were recovered to baseline 1evel 3 months after the use of contrast media.No patients underwent a maintenance hemodialysis.In the 19 patients with CIN,the levels of SUN and Scr were higher and Ccr was lower at day 1 and 2 after angiography than before the procedure (all P ＜ 0.05),but the parameters were decreased to preoperative level at day 6 after angiography (all P＞0.05).Logistic regression analysis showed that renal dysfunction,diabetes mellitus and severe renal artery stenosis were the major risk factors for contrast-induced nephropathy.Conclusions Low-osmoiar nonionic contrast used in angiography is safe for elderly patients if adequately hydrated with 0.9 ％ sodium chloride.The clinical risk factors for CIN are renal dysfunction,diabetes mellitus and severe renal artery stenosis.

ObjectiveTo reveal the relation between rhBNP and vascular remodeling,the relation between rhBNP and levels of serum high sensitive C reactive protein (hs-CRP).Methods20 male New Zealand rabbits were randomly divided into two groups.All the rabbits were constructed to be models of angioplasty with BC.After injury,the control group were feed with standard forage,the rhBNP group received standard forage plus sibeutaneous rhBNP [0.1mmg/(kg · day),20 days].The rabbits were killed 4weeks after initial injury.The injured segments were dissected free from arteria iliaca externa,processed for histological and morphological study by TD 2000 analysis system of pathology image.The data of vascular remodeling was determined.The levels of hs-CRP were measured at the beginning and the end of the experiment.ResultsThere was significant difference in AUIEM and AUEEM[ (643.2±134.06) μm2 vs (493.7±139.32) μm2 ; (1495.1±204.98)μm2 vs (1265.9±232.56)μm2,P ＜ 0.05 ],extremely significant difference in residual cavity areas and ratios of stenosis[ (519.1±93.47) μm2 vs (308.6±86.50) μm2;(18.68±7.72) μm2 vs (38.04±8.32) μm2,P ＜ 0.01 ].There was no significant difference between the areas of media (P＞ 0.05).rhBNP reduced the levels of hs-CRP on the 28th day.ConclusionsrhBNP can benefit vascular remodeling after angioplasty which might be through its anti -inflammatory action.