Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Objective:To estimate the burden of influenza-associated outpatient consultations in China from 2011 to 2021 surveillance years to provide a reference for developing influenza prevention, control strategies, and vaccination policies.Methods:Data on influenza-like illness (ILI) and virological confirmation of sentinel specimens from 2011 to 2021 surveillance years were extracted from China's national sentinel surveillance system. Generalized additive models were fitted to estimate influenza-associated excess ILI outpatient burden, accounting for seasonal baselines and meteorological factors.Results:Influenza was associated with an average of 1.66 (95% CI: 1.51-1.80) excess ILI consultations per 1 000 person-years (py) in China each year from 2011 to 2021 surveillance years. The influenza-associated outpatient burden was similar across different virus types/subtypes. Influenza A(H1N1)pdm09 led to a higher rate of influenza- associated ILI consultations [0.65 (95% CI: 0.53-0.76) per 1 000 py] compared to other types/subtypes. The age groups with the highest burdens were children aged 0-4 years and 5-14 years, with excess outpatient consultation rates of 15.23 (95% CI: 13.73-16.73) per 1 000 py and 13.53 (95% CI: 12.49-14.52) per 1 000 py, respectively. Conclusions:Influenza caused many outpatient consultations in China, particularly among children aged 0-14. Continuous influenza monitoring and disease burden assessment should be conducted, and close attention should be paid to the changing trends of various influenza virus types/subtypes. When formulating vaccination strategies, priority should be given to recommending vaccination for high-risk populations, such as children.

Objective:To estimate the burden of influenza-associated outpatient consultations in China from 2011 to 2021 surveillance years to provide a reference for developing influenza prevention, control strategies, and vaccination policies.Methods:Data on influenza-like illness (ILI) and virological confirmation of sentinel specimens from 2011 to 2021 surveillance years were extracted from China's national sentinel surveillance system. Generalized additive models were fitted to estimate influenza-associated excess ILI outpatient burden, accounting for seasonal baselines and meteorological factors.Results:Influenza was associated with an average of 1.66 (95% CI: 1.51-1.80) excess ILI consultations per 1 000 person-years (py) in China each year from 2011 to 2021 surveillance years. The influenza-associated outpatient burden was similar across different virus types/subtypes. Influenza A(H1N1)pdm09 led to a higher rate of influenza- associated ILI consultations [0.65 (95% CI: 0.53-0.76) per 1 000 py] compared to other types/subtypes. The age groups with the highest burdens were children aged 0-4 years and 5-14 years, with excess outpatient consultation rates of 15.23 (95% CI: 13.73-16.73) per 1 000 py and 13.53 (95% CI: 12.49-14.52) per 1 000 py, respectively. Conclusions:Influenza caused many outpatient consultations in China, particularly among children aged 0-14. Continuous influenza monitoring and disease burden assessment should be conducted, and close attention should be paid to the changing trends of various influenza virus types/subtypes. When formulating vaccination strategies, priority should be given to recommending vaccination for high-risk populations, such as children.

OBJECTIVE To estimate the quality markers of antioxidant activity for standard decoction of Schisandrae Chinensis Fructus.METHODS 15 batches of Schisandrae Chinensis Fructus standard decoctions were subjected to quality evaluation by ultra high-performance liquid chromatography(UPLC)based on single-marker(QAMS)method,before being summarized by chemometrics analysis.The antioxidant abilities of 15 batches of samples were determined by DPPH and ABTS methods,while gray correlation analy-sis(GRA)and the partial least squares regression(PLSR)methods were subsequently applied to investigating the relationship between the contents of 8 components and the antioxidant activity.Ultimately,molecule docking was utilized to explore the binding properties between candidate quality markers and the core targets of anti-oxidation,with the experimental verification being executed on the indi-vidual compound by in vitro anti-oxidation.RESULTS There was no remarkable difference between the results of QAMS and external standard method(ESM),with P valued greater than 0.05.And it was speculated that protocatechuic acid,gomisin A,schizantherin B and schisandrin B were the constituents of quality difference.Moreover,the 4 quality variation components were reckoned to be the al-ternative markers on antioxidant according to the results of GRA and PLSR.The molecule docking result also showed that 4 candidate quality markers presented good binding affinity with the antioxidant core targets.The antioxidant capacity was presumably originated from the collaborated effects by multi-components in the standard decoction of Schisandrae Chinensis Fructus.In the interim,protocate-chuic acid exhibited noteworthy antioxidant efficacy with dosage-depended manner in the results of single-compound verification,which was best conformed to the characteristics of quality markers and supposed to be the antioxidant quality marker for Schisandrae Chinensis Fructus standard decoction.CONCLUSION This research predicts the potential antioxidant substances on the basis of content deter-mination by UPLC and in vitro antioxidant assay,but also provides rational foundation for quality assessment on other preparations of Schisandrae Chinensis Fructus.

Objective:To explore the expression of endosialin, i.e., CD248 in human hypertrophic scars (HSs) and its regulatory effect on the phenotype of hypertrophic scar fibroblasts (HSFs).Methods:The method of experimental research was used. From March to May, 2023, 3 pediatric patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 2 females and 1 male, aged one year ten months to two years. The HS tissue resected during the surgery and the remaining full-thickness skin graft, i.e., normal skin tissue after full-thickness skin grafting were collected from the aforementioned pediatric patients for subsequent experiments. Using the aforementioned two types of tissue, the histological structures were observed by hematoxylin-eosin staining, collagen distribution was observed by Masson staining, and the expression of CD248 was observed and measured by immunohistochemical staining. The primary HSFs were isolated from HS tissue using explant culture technique, and the 3 rd to 5 th passages of HSFs were used in subsequent experiments. According to the random number table, HSFs were divided into immunoglobulin G78 (IgG78)-treated group and IgG control group, which were treated with 200 nmol/L human CD248 monoclonal antibody IgG78 and human IgG control antibody for 24 h, respectively. The mRNA expressions of collagen type Ⅰ (Col Ⅰ) and α-smooth muscle actin (α-SMA) in HSFs were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction, the protein expressions of Col Ⅰ and α-SMA in HSFs were detected by Western blotting, and the intracellular location and protein expressions of Col Ⅰ and α-SMA were detected by immunofluorescence method. The number of samples in each experiment was 3. Data were statistically analyzed with paired sample t test and independent sample t test. Results:Compared with those in normal skin tissue, the epidermis and dermis in HS tissue were significantly thicker, with massive accumulation and disordered arrangement of collagen in the dermis. The expression of CD248 in HS tissue was significantly upregulated compared with that in normal skin tissue ( t=5.29, P<0.05). At post treatment hour 24, the mRNA expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were 0.39±0.05 and 0.56±0.09, respectively, which were significantly lower than 1.00±0.07 and 1.00±0.08 in IgG control group, respectively (with t values of 11.87 and 6.49, respectively, P values all <0.05). The protein expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were 0.617±0.011 and 0.67±0.14, respectively, which were significantly lower than 1.259±0.052 and 1.23±0.16 in IgG control group, respectively (with t values of 20.92 and 4.52, respectively, P values all <0.05). At post treatment hour 24, immunofluorescence staining showed that Col Ⅰ and α-SMA mainly located in the cytoplasm of HSFs in the two groups, and the protein expressions of Col Ⅰ and α-SMA of HSFs in IgG78-treated group were obviously downregulated compared with those in IgG control group. Conclusions:The expression of CD248 is significantly upregulated in human HS. Targeted blockade of CD248 can significantly inhibit the collagen synthesis by HSFs and the transdifferentiation of HSFs into myofibroblasts.

Objective: To summarize the measures and experience of treatment in mass extremely severe burn patients. Methods: The clinical data and treatment of 8 extremely severe burn patients in August 2 Kunshan factory aluminum dust explosion accident who were admitted in the 100th Hospital of PLA on August 2nd, 2014, were retrospectively analyzed. There were 4 males and 4 females, aging 22-45 (34±7) years, with total burn area of 55%-98% [(89±15)%] total body surface area (TBSA) and full-thickness burn area of 45%-97% [(80±21)%] TBSA. All the 8 patients were accompanied with severe shock, inhalation injury, and blast injury. According to the requirements of former PLA General Logistics Department and Nanjing Military Command, a treatment team was set up including a special medical unit and a special care unit, with Chai Jiake from the First Affiliated Hospital of PLA General Hospital as the team leader, Zheng Qingyi from the 175th Hospital of PLA (the Affiliated Dongnan Hospital of Xiamen University) as the deputy leader, the 100th Hospital of PLA as the treatment base, and burn care, respiratory, nephrology, nursing specialists from the First Affiliated Hospital of PLA General Hospital, and the burn care experts and nursing staff from the 180th Hospital of PLA, 118th Hospital of PLA, 98th Hospital of PLA, and 175th Hospital of PLA, and nurses from the 85th Hospital of PLA, 455th Hospital of PLA, 101th Hospital of PLA, 113th Hospital of PLA as team members. Treatment strategies were adopted as unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns. With exception of one patient who received deep vein catheterization before admission, the other 7 patients were treated with deep vein catheterization 0.5 to 3.0 hours after admission to correct hypovolemic shock as soon as possible. Eight patients received tracheotomy, and 7 patients were treated with mechanical ventilation by ventilator in protective ventilation strategy with low tide volume and low volume pressure to assist breathing. Fiberoptic bronchoscopy was done one to three times for all the 8 patients to confirm airway injuries and healing status. Escharectomy and Meek dermatoplasty in the extremities of all the 8 patients were performed 3 to 6 days after injury for the first time. Escharectomy, microskin grafting, and covering of large pieces of allogeneic skin on the trunks of 4 patients were performed 11 to 16 days after injury for the second time. The broad-spectrum antibiotics were uniformly used at first time of anti-infective therapy, and then the antibiotics species were adjusted in time. The balance of internal environment was maintained and the visceral functions were protected. One special care unit was on responsibility of only one patient. Psychological intervention was performed on admission. The rehabilitative treatment was started at early stage and in company with the whole treatment. Results: Acute renal injury occurred in 5 patients within 36 hours after injury and their renal function was restored to normal 4 days after injury due to active adjustment of fluid resuscitation program. No pulmonary complications, such as severe pulmonary infection and ventilator-associated pneumonia, occurred in the survived patients. One of the 8 patients died, and the other 7 patients were cured successfully. The wounds were basically healed in 2 patients in 26 or 27 days by 2 or 3 times of operation, and in 5 patients by 4 or 5 times of operation. The basic wound healing time was 26-64 (48±15) days for all the 7 patients. Conclusions Treatment strategies of unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns are the bases to successful treatment. Correcting shock as soon as possible is the prerequisite and closing wound as soon as possible is the key to successful treatment. Comprehensive treatment measures, such as maintaining and regulating the function of viscera, improving the body immunity, and preventing and treating the complications, are the important components to successful treatment. It is emphasized that in the treatment of mass extremely severe burn patients, specialist burn treatment should always be in the dominant position, and other related disciplines may play a part in auxiliary function.

Objective To evaluate the feasibility and clinical efficacy of intra-abdominal exposure instruments in laparoendoscopic single-port nephrectomy(LESS-N).Method From February 2012 to July 2016,61 cases of LESS-N were performed in our center.There were 34 males and 27 females with a mean age of (60.3 ± 9.4) years old (ranging 36-72 years old).There were thirty-nine cases of renal tumors and twenty two cases of nonfunctioning kidney.The patients were divided into two groups.Group A included 39 cases that underwent conventional LESS-N (22 radical nephrectomy/17 simple nephrectomy).Group B included 22 cases that underwent intra-abdominal exposure instruments assisted LESS-N (17 radical nephrectomy/5 simple nephrectomy).The perioperative and postoperative data were collected and analyzed retrospectively.Results All the procedures of these two groups were completed successfully.In Group A,four patients were added one 5 cm additional trocar and two patients were converted to open surgery.No additional trocars or conversion to open surgery were needed in Group B.For LESS radical nephrectomy,there were no significant differences of mean tumor diameter (5.7cm vs.5.4 cm,P =0.65) between two groups.The average operative time was (95.1 ± 43.9) min in Group B which was lower than that in Group A (127.4 ± 61.9) min (P ＜ 0.01).The mean renal vascular processing time was declined from (25.4 ± 10.1)rmin in Group A to (18.8 ± 8.9)min in Group B (P ＜ 0.05).The mean estimated blood loss was (128.6 ± 51.1) ml in Group A and (98.7 ±-57.6) ml in Group B (P ＜ 0.05).No severe intraoperative and postoperative complications occurred in both group.Conclusions Intra-abdominal exposure instruments are feasible and effective for LESS-N.This system may shorten the operation time,reduce the amount of bleeding and improve surgical accuracy.

Objectives To identify the Francisella strain isolated from blood of a patient with drowning-associated pneumonia.Methods The whole genome of the strain,designated Wenzhou1,was sequenced using the high throughput sequencing technology by 2000/miSeq system of Illumina platform,and the obtained genome draft was assembled by MicrobeTrakr Plus software.The phylogenetic neighbors of Wenzhou1 were obtained by NCBI BLAST analysis from GenBank database for the gene sequences of 16S rRNA,malate dehydrogenase(mdh),DNA-directed RNA polymerase subunit beta (rpoB) and succinate dehydrogenase subunit alpha (sdhA).The average nucleotide identity(ANI) between Wenzhou1 and its phylogenetic neighbors was analyzed by the software OrthoANI using NCBI BLAST search under the Java Runtime Environment Version 8.Results The genome size of Wenzhou1 was 1.96 × 106 bp,containing 74 contigs.The genomic G + C mol％ of Wenzhou1 was 32.1％,which was similar to the other species of genus Francisella and Allofranicella.Based on the analysis of NCBI BLAST of GenBank for the similarities of 16S rRNA gene,mdh gene,rpoB gene and sdbA gene sequences,Wenzhou1 was most closely related to F.hispaniensis FSC454 and Francisella cf.novicida 3523.The ANI of Wenzhou1 was 97.8％ to F.hispaniensis FSC454,97.5％ to 97.6％ to Francisella cf.novicida 3523,but only 91.3％ to 91.5％ to the four subspecies of F.tularensis.Conclusion ANI analysis based on whole genome sequence should be an accurate,effective method for bacterial identification.Wenzhou1 could be identified as F.hispaniensis by ANI with high-throughput whole genome sequencing technology.

[ ABSTRACT] AIM:To study the effect of idazoxan ( IDA) on the permeability of blood-brain barrier ( BBB) and the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in mouse ex-perimental autoimmune encephalomyelitis (EAE).METHODS: Female C57BL/6 mice (n=36) were randomly divided into control group, EAE group and IDA group, with 12 mice in each group.EAE was induced by myelin oligodendrocyte glycoprotein 35-55 ( MOG35-55 ) .IDA (2 mg/kg, ip, bid) was administered for 15 d after immunization.The neurological defects of the mice were observed daily and scored.The pathological changes were observed under microscope with HE stai-ning and LFB myelin staining.The BBB permeability was detected by Evans blue extravasation.The expression of MMP-9 and TIMP-1 in the brain of EAE mice was determined by Western blotting.RESULTS: Compared with EAE group, the score of neurological defects in IDA group was decreased, the inflammation was relieved, the BBB permeability was re-duced, and the expression MMP-9 and the ratio of MMP-9/TIMP-1 were decreased ( P<0.05 ) .CONCLUSION: The neuroprotective effect of IDA on mouse EAE might be related to the down-regulation of MMP-9 and the ratio of MMP-9/TIMP-1, thus reducing the degradation of BBB and the permeability of BBB, and ameliorating the pathologic process of EAE.

Objective The mechanism of delaying flap with the minimal invasive surgery was approached to understand its effects on the whole delayed survival of skin flaps thoroughly so as to provide the rationale for its clinical use.Methods 80 male or female Wistar rats were randomly subdivided into two groups:delayed by the minimal invasive surgery,and immediately transfer without delay.Flaps in each group delayed were cut at 1,2,3 and 4 weeks,respectively.The flap was designed at the lower back of rat,with the size of 5 cm × 1 cm,crossing the middle area for 2.5 cm and including stem of iliac branch from iliolumbar artery.2 weeks after second operation,the survival area,capillary density and content of lactic acid of the flaps in each group were examined,and the survival of the falps delayed by the minimal invasive surgery was compared.Results The longer delaying time,and the higher survival rate were observed in the experimental group.Delaying for 3 weeks and 4 weeks,the survival rate was (86.13 ±1.13) ％,(93.49 ± 1.15) ％,respectively,in the experimental group.While in control group,the survival rate was no more than 63％.The longer delaying time,the higher the capillary density were noted in two groups,but 3 weeks delayed group equally matched to the 4 weeks delayed group.In the experimental group,the content of lactic acid increased peaked in 1 week delayed group,then fell-down gradually,but kept steady in 3 and 4 weeks delayed group.The content of lactic acid in the control group kept steady.Conclusions The experimental model is selected as cross-area axial flap on the lower back of rats.The minimal invasive surgery plays the same role as in delaying flaps,which causes vasoconstriction,resulting in disorder of internal environment,ischemia and hypoxia,finally vasodilatation.The more ramus anastomosis,the more survival rate of the flap.