Objective To explore the expression and significance of neutrophil extracellular traps(NETs)in peripheral blood of primary Sj?gren's syndrome(pSS)patients across different disease activity levels,and the predictive value of NETs and routine laboratory markers antithrombin Ⅲ(AT Ⅲ),alkaline phosphatase(ALP)and carbohydrate antigen 125(CA125)for pSS disease activity.Methods A total of 94 newly diagnosed pSS patients at the Affiliated Lianyungang Hospital of Xuzhou Medical University from October 2021 to December 2023 were categorized into active(n=49)and non-active(n=45)groups based on the European League Against Rheumatism(EULAR)Sj?gren's Syndrome disease activity index(ESSDAI).The levels of NETs biomarkers,namely serum myeloperoxidase(MPO)-DNA,were measured using ELISA.Laboratory routine indicators and MPO-DNA were integrated into multivariate Logistic regression to screen for independent influencing factors of pSS disease activity.Pearson's correlation was used to evaluate the relationship between MPO-DNA levels and ESSDAI scores.The efficacy of MPO-DNA alone or in combination with AT Ⅲ,ALP and CA125,for predictors of disease activity was evaluated using ROC curve.Results Serum MPO-DNA(23.884±3.494 μg/L),ALP(80.159±34.318 U/L)and CA125(20.300±16.560 U/ml)levels of active pSS patients were higher than those in the non-active patients(19.024±3.324 μ g/L,67.500±21.166U/L,13.200±6.340 U/ml),while AT Ⅲ(89.180±15.040 ng/ml)was lower than that in non-active patients(94.650±11.620 ng/ml),with significant differences(t=-7.921,-2.426,-2.925,2.094,all P＜0.05).Multivariate Logistic regression analysis showed laboratory indicator MPO-DNA,ALP and CA125 were independent risk factors,while AT Ⅲ was an independent protective factor(all P＜0.05).MPO-DNA was positively correlated with ESSDAI scores(r=0.602,P＜0.01).The AUC(95％CI)of the combination of ALP,CA125 and AT Ⅲ for predicting disease activity in pSS was 0.711(0.612～0.810).The AUC(95％CI)of MPO-DNA alone for predicting disease activity in pSS was 0.837(0.758～0.915),and the AUC(95％CI)of combination of MPO-DNA,ALP,CA125 and AT Ⅲ for predicting disease activity in pSS was 0.866(0.797～0.935),showing an improving in the predictive value.Conclusion The involvement of NETs in the occurrence and expression levels of pSS is related to its disease activity.NETs combined with ALP,CA125 and AT Ⅲ have effective diagnostic performance for the disease activity of pSS.This tool can serve as a biological indicator for predicting the disease activity of pSS.

Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that CRLF1 was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of CRLF1 had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for CRLF1 up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.
Animals ; Humans ; Mice ; Disease Models, Animal ; Fibroblasts/metabolism* ; Fibrosis ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 3/metabolism* ; Myocardial Infarction/metabolism* ; Receptors, Cytokine/metabolism* ; Signal Transduction ; Transforming Growth Factor beta1/pharmacology*

OBJECTIVE To systematically evaluate the hemostatic effect and safety of snake venom hemocoagulase drugs in abdominal surgery， so as to provide evidence-based evidence for clinic. METHODS Retrieved from Embase， Cochrane Library， PubMed， China Biomedical Literature Database， CNKI and Wanfang database， randomized controlled trials （RCTs） about 3 kinds of snake venom hemocoagulase drugs （Hemocoagulase injection， Hemocoagulase Bothrops atrox for injection， Haemocoagulase Agkistrodon for injection） in abdominal surgery were collected from the establishment of the database to Aug. 2023. Screening， quality evaluation， and data extraction were conducted on literature according to the inclusion and exclusion criteria， and Cochrane 5.1 was used for literature quality evaluation. The risk bias diagram and network diagram were drawn by Stata 15.1 software， and the Bayesian network meta-analysis was carried out by using R 3.6.2 software and Markov chain-Monte Carlo method. RESULTS A total of 11 studies were included， involving 1 401 patients， 852 in the study group， and 549 in the control group. In terms of hemostatic effect， Hemocoagulase injection was significantly superior to Haemocoagulase Agkistrodon for injection [MD＝－2.45， 95%CI （－4.39，－0.24）， P＜0.05]， and the probability of reducing intraoperative bleeding was ranked as follows： Hemocoagulase injection＞hemocoagulase B. atrox for injection＞Haemocoagulase Agkistrodon for injection； in terms of safety， there was no statistically significant difference between the three snake venom hemocoagulase drugs and placebo （P＞0.05）. CONCLUSIONS The hemostatic effect of Hemocoagulase injection in abdominal surgery is significantly better than that of Haemocoagulase Agkistrodon for injection； all three snake venom hemocoagulase drugs have good safety.

Objective:To design a tracheotomy cannula cuff filling device for hyperbaric oxygen therapy, which is convenient for clinical operation, improves work efficiency and reduces the incidence of aspiration pneumonia.Methods:This study was a randomized controlled trial. From July 2020 to June 2022, 90 patients with tracheotomy who were treated with hyperbaric oxygen in the First Hospital of Jiaxing were selected as the research objects. According to the random number table method, the patients were divided into the experimental group and the control group, with 45 cases in each group. In the experimental group, the cuff pressure was maintained by the tracheotomy cannula cuff filling device, and in the control group, the traditional water injection method was used to maintain the cuff pressure. The operation time, infection index and incidence of aspiration pneumonia were compared between the two groups.Results:The operation time in the experimental group was (6.33 ± 1.31) s lower than that in the control group (40.96 ± 3.70) s, and the difference was statistically significant ( t=-59.11, P<0.05). Body temperature, C-reactive protein and procalcitonin after treatment in the experimental group were (36.91 ± 0.83) ℃, (34.59 ± 16.25) mg/L, (1.57 ± 0.82) μg/L, respectively, lower than those in the control group (37.42 ± 0.72) ℃, (44.18 ± 18.10) mg/L, (2.45 ± 0.92) μg/L, the differences were statistically significant ( t=-3.09, -2.64, -4.73, all P<0.05). The difference of white blood cell count post-treatment between the two groups was not statistically significant ( P>0.05). The incidence of aspiration pneumonia in the experimental group was 11.11%(5/45) lower than 31.11%(14/45) in the control group, and the difference was statistically significant ( χ2=5.17, P<0.05). Conclusions:The application of tracheotomy cannula cuff filling device can simplify the operation process, reduce the incidence of infection and aspiration pneumonia, and optimize the clinical work.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Objective To analyze the effect of different anesthesia induction time on postoperative circadian rhythm in patients undergoing robot-assisted radical prostatectomy.Methods A total of 103 pa-tients,aged 50-85 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ,undergoing robot-assisted radi-cal prostatectomy from January 2022 to October 2022 were recruited.The patients were grouped according to the induction time:the morning 8:00-11:59 group(group M,n=53)and the afternoon 12:00-18:00 group(group A,n=50).D'Amico risk grade,duration of anesthesia,number of effective com-pressions of analgesic pump(D1)and actual compressions(D2)were recorded,D1/D2 were calculated.HR,MAP,SpO2 were recorded at 5 minutes after entrying the operation room(T0),5 minutes after anes-thesia induction(T,),5 minutes after the surgery start(T2),60 minutes after the surgery start(T3),at the end of surgery(T4)and 5 minutes after extubation(T5).BIS at T1-T4 were recorded.Sleeping status was assessed by the Athens insomnia scale(AIS)1 day before surgery,1 day and 3 days after surgery,and pain level was assessed 1 and 3 days after surgery using the digital rating scale(NRS).According to the re-sults of the morningness-eveningness questionnaire of sleep-wake assessment(MEQ-SA)1 day before surgery and 3 days after surgery,the patients'circadian rhythm was determined.Results There were no statistically significant differences in D'Amico risk grade,duration of anesthesia,D1/D2,HR,MAP,SpO2 and BIS at different time point,AIS scores 1 day before surgery,1 day and 3 days after surgery,and NRS scores 1 day and 3 days after surgery between the two groups.In group M,there were 11 cases(21％)of circadian rhythm changes,of which 5 people's circadian rhythm changed to"later"and 6 people's circadian rhythm changed to"earlier".In group A,there were 3 cases(6％)of circadian rhythm changes,of which 1 person's circadian rhythm changed to"later"and 2 people's circadian rhythm changed to"earlier".The rate of circadian rhythm change in group M was significantly higher than that in group A(P＜0.05).Conclusion The incidence of perioperative circadian rhythm alteration is significantly higher in patients undergoing robot-assisted radical prostatectomy who starts anesthesia in the morning than those in the after-noon.

Non-invasive mechanical ventilation(NIV)is increasingly being used as a respiratory support technique in clinical practice.However,the pressure-related injuries should not be overlooked.In order to prevent local pressure injuries caused by NIV technology,a series of preventive measures have been adopted in clinical work.These measures include the use of dressings to provide pressure relief to the local skin.Currently,in clinical practice,when using preventive dressings,nurses need to cut them themselves based on the physiological structure of the patient's nose,forehead,or face.However,precise cutting can be challenging.If the dressing is cut too small,it may not provide adequate prevention,and if it's cut too large,it can cover too much skin,affecting the nurse's observation and the patient's comfort.Additionally,during NIV treatment,the preventive dressings used may become curled or displaced,requiring nurses to re-cut and replace them.This process inevitably leads to material wastage,increasing the cost of dressing use for patients.Moreover,the cutting tools used must meet infection control requirements,adding to the nursing workload and reducing the compliance of nurses in changing dressings.Our research team has designed a ready-made pressure injury prevention dressing component for use with NIV masks to prevent pressure injuries to the nasal and facial areas.It is precisely designed,flexible in composition,easy to use,and can provide multiple usage modes.It effectively combines emergency care with pressure relief measures,reducing the occurrence of pressure injuries to the patient's nasal and facial areas.This improves patient comfort and treatment compliance,facilitates technology-based nursing,and enhances clinical efficiency.It has significant clinical application value and has been granted a National Utility Model Patent(ZL 202020529121.6).

OBJECTIVE According to the rapid Health Technology Assessment （HTA） for postmenopausal osteoporosis （PMOP），To evaluate the efficacy ，safety and economy of calcitonin in the treatment of PMOP ，and provide evidence -based medical evidence for clinical drug decision . METHODS Retrieved from the Cochrane Library ，PubMed，Embase，CNKI，Wanfang database，CBM and HTA official website ，systematic review/meta -analysis，pharmacoeconomics research and HTA reports about calcitonin in the treatment of PMOP were retrieved from the inception to Sept . 30th，2022. Two researchers independently carried out screening ，data extraction and quality evaluation ，and analyzed the data results descriptively . RESULTS A total of 18 studies were included ，including 12 SR/meta-analysis and 6 economic studies ，and no HTA report was retrieved . In terms of effectiveness ， the results of the included studies were basically consistent ：calcitonin had a certain advantage in reducing the incidence of vertebral fracture compared with calcium and lasoxifene alone ，but did not show clinical advantage compared with other positive drugs . In terms of reducing the incidence of non -vertebral fractures ， calcitonin had some advantages ，compared with calcium al one and raloxifene ，but did not show clinical advantage compared with other positive drugs . In terms of improving bone mineral density（BMD），only 2 studies showed that calcitonin had a certain advantage over calcium but no advantage was observed compared with other positive drugs . In terms of improving non - vertebral BMD ，only 1 study showed that calcitonin combined with calcium had certain advantages compared with calcium alone in improving femoral BMD ，but there was no advantage compared with other positive drugs . In terms of lowering bone pain scores ， both included studies demonstrated short -term benefit of nasal calcitonin in reducing acute pain was found in patients with vertebral fractures，but not in patients with chronic pain . In terms of safety ，the three included studies showed that calcitonin caused mild adverse reactions compared with other positive drugs ，but there was a risk of malignant tumors after long -term use . In terms of economy，only 1 study showed the use of nasal calcitonin in the treatment of PMOP had more economic advantages than no treatment or etidronate . CONCLUSIONS Calcitonin has a certain effect on reducing acute pain in patients with PMOP vertebral fracture，and its safety needs further investigation . No obvious economic advantage has been found .

OBJECTIVE：To analyze the effects of mangiferin （MGF）on glucose and lipid metabolism in insulin resistance （IR）HepG2 cells，and to explore the potential mechanism. METHODS ：Using human hepatoma HepG 2 cells as research objects ， 1 mmol/L palmitic acid and 2 mmol/L oleic acid were used to establish the IR-HepG 2 cell model. Using metformin hydrochloride as positive control ，the effects of low-concentration ，medium-concentration and high-concentration MGF （125，250，500 μmol/L）on the corrected glucose consumption ，the contents of triglyceride （TG）and total cholesterol （TC）in IR-HepG 2 cells were detected. The mRNA expression of APN ，AdipoR2，APPL1，AMPK in the upstream of AMPK signaling pathway and IRS- 1，Akt and GLUT4 in the downstream insulin signaling pathway were detected by RT-PCR. The phosphorylation level of AMPK protein was detected by Western blot assay. RESULTS ：Compared with control group ，corrected glucose consumption ，mRNA expression of APN，AdipoR2，APPL1，AMPK，IRS-1 and GLUT 4，as well as the phosphorylation level of AMPK protein were decreased significantly in model group ，while the contents of TG and TC were increased significantly （P＜0.05 or P＜0.01）. Compared with model group ， corrected glucose consumption ， mRNA expression of APN （except for MGF medium-concentration and high-concentration groups ），AdipoR2，APPL1，AMPK（except for MGF medium-concentration and high-concentration groups ）， IRS-1（except for MGF medium-concentration and high-concentration groups ），Akt（except for positive control group ），GLUT4 （except for MGF high-concentration group ）were increased significantly in administration groups ，while the contents of TG and TC were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Mangiferin may activate APN ，which is the upstream target of pathway ，and then regulate AMPK signaling pathway ，so as to promote glucose uptake of IR-HepG 2 cells，reduce TG and TC contents，and improve IR and abnormal glucose and lipid metabolism.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.