Objective To evaluate the therapeutic effects of different intracranial pressure lower-ing regimens in patients with acute large-area cerebral infarction based on electrical impedance tomo-graphy(EIT)technology.Methods A total of 75 patients with acute large-area cerebral infarction were selected as the study subjects and randomly divided into study group(n=40,using mannitol combined with albumin to decrease intracranial pressure)and control group(n=35,using mannitol alone to decrease intracranial pressure).EIT technology was used to continuously monitor the changes in intracranial pressure within 48 hours in the patients.Clinical data of the two groups were collected,and the 24-hour intracranial pressure change rate,48-hour intracranial pressure change rate,ICU stay duration,hospitalization duration,antibiotic use duration,and National Institutes of Health Stroke Scale(NIHSS)score at discharge were observed and compared between the two groups.A 90-day sur-vival follow-up was also conducted.Results There was no statistically significant difference in the 24-hour intracranial pressure change rate between the two groups(P＞0.05).The 48-hour intracrani-al pressure change rate in the study group was higher than that in the control group,and the difference was statistically significant(P＜0.05).The ICU stay duration,hospitalization duration,and antibiotic use duration in the study group were all shorter than those in the control group,and the NIHSS score at discharge in the study group was lower than that in the control group,with statistically significant differences(P＜0.05).The follow-up results showed that the survival duration in the study group was longer than that in the control group,and the 90-day cumulative survival rate in the study group was higher than that in the control group,but the differences were not statistically significant(P＞0.05).The modified Rankin Scale score in the study group was lower than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion Compared with the use of mannitol alone,early use of mannitol combined with albumin can effectively decrease the in-tracranial pressure within 48 hours,shorten the hospitalization duration,and improve neurological function in patients with acute large-area cerebral infarction.

Diffuse pediatric-type high-grade glioma (pHGG), H3- and isocitrate dehydrogenase (IDH)-wild-type, is a World Health Organization (WHO) grade 4 diffuse glioma with malignant histological features, which typically affects in children and adolescents. This multidisciplinary treatment case involves a 24-year-old young female patient initially diagnosed via biopsy. After concurrent chemoradiotherapy reduced the tumor size, complete resection was achieved, followed by adjuvant therapy with temozolomide and regorafenib. After recurrence, the tumor was resected again, and a second course of radiotherapy was administered, but the disease ultimately progressed rapidly, with an overall survival exceeding 32 months. pHGGs are highly malignant, aggressive, and associated with poor prognosis. Accurate diagnosis and targeted intervention require close collaboration among a multidisciplinary team, which highlights the critical value of multidisciplinary manage-ment in clinical practice.

Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

Objective To establish a new program of blood cell processing apparatus(NGL-BBS)for the preparation of washed mixed plateletsand to study the effect on biological activity of platelets compared with tradi-tional manual method.Methods Mixed concentrated platelets were separated and prepared from whole blood by white membrane method.Blood cell processing apparatus with new program set(experimental group)and manual method(control group)was used for thepreparation of washed mixed platelets.The expression rate of CD62P and CD63 in the two groups of washed mixed platelets was compared by flow-cytometry.Thrombus elastography(TEG)was used to measure and compare the MA value between the two groups.Results The expression rate of CD62P and CD63 in the experimental group was lower than that in the control group(t = 4.11,P<0.01;t = 10.78,P<0.01).TheTEG MA valueof the experimental group was higher than that of the control group(t = 6.67,P<0.01).Conclusion The present study demonstrates that the use of NGL-BBS for the preparation of washed mixed plate-lets has a lesser impact on biological activity compared to manual preparation methods.

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

Dengue; dengue virus; dengue vaccine; Aedes

Objective To analyze the anesthetic effect and hemodynamic impact of oxybutynin(OBI)combined with dexmedetomidine(DEX)on patients undergoing endoscopic dacryocystorhinostomy(En-DCR).Methods Patients who underwent En-DCR from February 2024 to May 2024 at Mianyang Wanjiang Eye Hospital were recruited.They were randomly divided into the DEX group(DEX administration only)and the combined group(DEX combined with OLI administration)according to the random number table method.The primary observational index in this study was the 24-h postoperative pain numerical rating scale(NRS)scores.The secondary observation indexes were heart rate(HR),mean arterial pressure(MAP),respiratory recovery time(SRT),extubation time(ET)and awakening time(AT),peak systolic value(PSV),end-diastolic blood flow velocity(EDV),resistance index(RI)and blood flow(BF).The occurrence of adverse events in patients during hospitalization was observed and recorded.Results A total of 80 patients were included in the study,with 40 in each of the DEX group and the combined group.In terms of analgesia,the NRS scores in the combined group were lower than those in the DEX group at T1(within 0.5 h after catheter removal),T2(4 h postoperatively),T3(8 h postoperatively),and T4(24 h postoperatively)(P＜0.05),and the remedial analgesia rate in the combined group was significantly lower than that in the DEX group(P＜0.05).Regarding anesthetic effects,HR and MAP at time points T6(during induction of anesthesia),T7(intraoperatively)and T8(during resuscitation)were lower in the combined group than in the DEX group(P＜0.05);and SRT,ET and AT were shorter in the combined group compared with the DEX group(P＜0.05).In terms of hemodynamics,at 24 h postoperatively,PSV,EDV and BF were significantly higher in both groups compared with those before anesthesia,whereas RI was significantly lower than before anesthesia(P＜0.05);PSV,EDV and BF were higher in the combined group than those in the DEX group,and RI was lower than that in the DEX group(P＜0.05).Regarding adverse reactions,the incidence of adverse reactions in the combined group was significantly lower than that in the DEX group(P＜0.05).Conclusion OLI combined with DEX prophylactic analgesia for patients with En-DCR is effective,not only to reduce postoperative pain,stabilize hemodynamics,shorten the time of extubation and awakening,and reduce the incidence of adverse reactions.

Objective:To evaluate the clinical efficacy of pushing reduction with our self-designed spinal fracture reduction device in the treatment of A3N0/1 thoracolumbar fractures.Methods:A retrospective study was conducted to analyze the medical records of 53 patients who had undergone surgery for thoracolumbar vertebrae fracture at Department of Minimally Invasive Spine Surgery, Zhengzhou Orthopedic Hospital from January 2019 to January 2022. All patients were treated by internal fixation via the Wiltse approach and bone grafting through the pedicle of the injured vertebrae. Clinical data: 35 males and 18 females; age: (37.8±10.2) years; injured segments: 23 cases at the thoracic spine and 30 cases at the lumbar spine; time from injury to surgery: (3.3±1.5) days. According to whether our self-designed spinal fracture reduction device was used or not, the patients were assigned into group A (23 cases) in which the injured vertebrae were pushed and reduced using our novel spinal fracture reduction device after vertebral distraction reduction by the pedicle screw and group B (30 cases) in which the injured vertebrae were distracted and reduced using the pedicle screw alone. The operation time, intraoperative blood loss and complications were compared between the 2 groups. The anterior vertebral body height ratio (AVBHr), middle vertebral body height ratio (MVBHr), posterior vertebral body height ratio (PVBHr), Cobb angle of the injured vertebra, visual analogue scale (VAS) and Oswestry disability index (ODI) at preoperation, postoperative 3 and 6 months, and the last follow-up were compared between the 2 groups.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (16.3±5.9) months. All incisions healed at one stage postoperatively without any related complications. The operation time in group A was significantly longer than that in group B [(115.1±16.6) min. versus (101.0±11.5) min.], the intraoperative blood loss in group A was significantly greater than that in group B [(136.5±17.0) mL versus (121.6±19.8) mL], the MVBHr at postoperative 3 months in group A (93.9%±4.0%) was significantly better than that in group B (83.3%±7.6%), and the MVBHr, AVBHr, Cobb angle, VAS, and ODI at the last follow-up in group A [86.6%±5.5%, 89.8%±4.1%, 4°(4°, 6°), 1 (0, 1) point, and 4.7%±2.0%] were significantly better than those in group B [78.0% (74.0%, 79.0%), 84.5%±4.9%, 12.2°±3.3°, 2 (1, 3) points, and 7.3%±2.7%] (all P<0.05). However, there was no statistically significant difference in PVBHr between the 2 groups at postoperative 3 months or at the last follow-up ( P>0.05). Conclusion:In the treatment of A3N0/1 thoracolumbar fractures, pushing reduction with our self-designed spinal fracture reduction device can directly and effectively reduce the fracture zone of the injured vertebra, which is conducive to maintaining postoperative vertebral reduction, reducing vertebral height loss and kyphotic deformity at a later stage, relieving lumbar pain and improving lumbar spine function.

Ossification of the posterior longitudinal ligament (OPLL) is a condition comprising ectopic bone formation from spinal ligaments. This disease is a leading cause of myelopathy in the Asian population. However, the molecular mechanism underlying OPLL and efficient preventive interventions remain unclear. Here, we performed single-cell RNA sequencing and revealed that type I interferon (IFN) signaling was activated in the ossified ligament of patients with OPLL. We also observed that IFN-β stimulation promoted the osteogenic differentiation of preosteoblasts in vitro and activated the ossification-related gene SPP1, thereby confirming the single-cell RNA sequencing findings. Further, blocking the IFN-α/β subunit 1 receptor (IFNAR1) using an anti-IFNAR1 neutralizing antibody markedly suppressed osteogenic differentiation. Together, these results demonstrated that the type I IFN signaling pathway facilitated ligament ossification, and the blockade of this signaling might provide a foundation for the prevention of OPLL.
Humans ; Signal Transduction ; Interferon Type I/metabolism* ; Ossification of Posterior Longitudinal Ligament/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Osteogenesis/genetics* ; Receptor, Interferon alpha-beta/metabolism* ; Male ; Female ; Cell Differentiation ; Middle Aged

Objective To investigate the effect of esketamine combined with sufentanil for postoperative patient-controlled intravenous analgesia(PCIA)on rebound pain after single nerve block.Methods From January 2021 to December 2022,80 patients undergoing upper limb fracture surgery in Jinshan Hospital,Fudan University with single nerve block anesthesia were included and randomly divided into two groups:the Ket group(esketamine combined with sufentanil PCIA)and the Ctrl group(sufentanil PCIA),with 40 patients in each group.Several indicators were recorded,including pain scores at 8 h,12 h,24 h,and 48 h postoperatively,the time to first pain and its score,pain scores 30 min after pressing the PCIA pump self-control button,as well as opioid consumption at 24 h and 48 h postoperatively,and the number of PCIA button presses.Rebound pain was defined as a sudden transition from"no pain"to"severe pain"(NRS ≥ 7)requiring pressing the PCIA self-control button.Results Rebound pain occurred in 17(45.95％)patients in the Ctrl group and 12(36.36％)patients in the Ket group,with no statistically significant difference.The Ket group had significantly lower sufentanil consumption and fewer PCIA presses at 24 h postoperatively compared to the Ctrl group(P=0.007).At 48 h postoperatively,there was no significant difference in sufentanil consumption and PCIA presses among patients who experienced rebound pain in the two groups.At 30 min after pressing the PCIA button for breakthrough pain,12 patients(100.00％)in the Ket group had NRS＜4,compared to 3 patients(17.65％)in the Ctrl group,with a statistically significant difference(P=0.02).Conclusions Compared with using sufentanil alone for PCIA,the combination of esketamine and sufentanil does not reduce the incidence of rebound pain following single nerve block in upper limb fracture surgery.However,the combination of esketamine and sufentanil may provide a faster relief of rebound pain.