BACKGROUND:Traumatic brain injury is a condition in which the normal function of the brain is disrupted by a bump or impact to the head.It is necessary to find effective treatments and objective targets that can help doctors diagnose the injury status and restore the brain function of patients. OBJECTIVE:To explore the effect of electroacupuncture combined with low-frequency transcranial ultrasound stimulation on the electroencephalographic signals of rats with traumatic brain injury. METHODS:Forty 6-week-old SPF male Sprague-Dawley rats were randomly divided into five groups:sham group,model group,electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group(electroacupuncture+low-frequency transcranial ultrasound stimulation),with eight rats in each group.Feeney weight-drop method was used to establish the animal model of traumatic brain injury.In the sham group,the bone window was only opened without impact.Interventions were started at 1 day after modeling.Electroacupuncture in the electroacupuncture group,low-frequency transcranial ultrasound stimulation in the low-frequency transcranial ultrasound stimulation group,and electroacupuncture+low-frequency transcranial ultrasound stimulation in the combined group were performed for days in total.The modified neurological severity scale score for assessing rats'neurological deficits was performed at 8 hours after modeling.The percentage of spontaneous alternation behavior in the Y-maze was measured at 7 days after modeling.Then,the electroencephalographic signals were collected and electroencephalographic data of α,β,θ,and δ waves were extracted by fast Fourier transform,and the value of oscillation amplitude and energy ratio were calculated in α,β,θ,and δ waves,as well as the Lempel-Ziv complexity and sample entropy. RESULTS AND CONCLUSION:Compared with the sham group,the modified neurological severity scale scores in the model group,electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group were significantly increased at 8 hours after modeling(P<0.05).Compared with the sham group,the value of oscillation amplitude in δ wave and the value of δ energy ratio were significantly increased in the model group at 7 days after modeling,meanwhile the percentage of spontaneous alternation behavior in Y-maze,and the value of α/β energy ratio,Lempel-Ziv complexity,and sample entropy were significantly decreased(P<0.05).Compared with the model group,the value of oscillation amplitude in α and δ waves was significantly decreased in the combined group(P<0.05),while the value of α/β energy ratio was significantly increased(P<0.05)and the value of δ energy ratio was significantly decreased(P<0.05)in the electroacupuncture group,low-frequency transcranial ultrasound stimulation group and combined group.Compared with the electroacupuncture group and low-frequency transcranial ultrasound stimulation group,the value of δ energy ratio was significantly decreased in the combined group(P<0.05),while the percentage of spontaneous alternation behavior,the value of α/β energy ratio,the Lempel-Ziv complexity,and the sample entropy were significantly increased(P<0.05).To conclude,abnormal electroencephalographic signals can appear in rats with traumatic brain injury,while the electroacupuncture combined with low-frequency transcranial ultrasound stimulation can alleviate the abnormal electroencephalographic signals in rats,which suggests the electroencephalographic frequency domain value and nonlinear features can be used to assess the severity of traumatic brain injury.

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.

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.

Objective:To explore the clinical efficacy of apatinib combined with tirelizumab in the treatment of advanced gastric cancer patients who failed first-line chemotherapy, as well as its impact on peripheral blood tumor angiogenesis regulatory factor levels and long-term survival.Methods:A prospective study was conducted on 144 advanced gastric cancer patients who failed first-line chemotherapy and were admitted to the Handan Central Hospital from January 2020 to December 2021. They were divided into two groups using a random number table method, with 72 patients in each group. The control group was treated with tirezizumab alone, while the observation group was treated with apatinib combined with tirezizumab. After four consecutive courses of treatment, the short-term efficacy of both groups was observed. We compared the levels of serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA724, CA125], tumor angiogenesis regulatory factors [vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1 α), insulin-like growth factor-1 (IGF-1), matrix metalloproteinase-9 (MMP-9)], and quality of life scores between two groups before and after treatment. Long term follow-up was conducted on all patients, and the long-term survival status of two groups was statistically analyzed. Two groups of adverse reactions were compared.Results:The objective remission rate and disease control rate (51.39%, 80.56%) of the observation group were significantly higher than those of the control group (31.94%, 61.11%, all P<0.05). After treatment, the serum levels of CEA, CA199, CA724, CA125, VEGF, SDF-1α, IGF-1, and MMP-9 in both groups were significantly reduced compared with those before treatment (all P<0.05), and the observed group showed a more significant decrease in the above indicators (all P<0.05). After treatment, the scores of physical function, emotional function, social function, role function, and overall health status in the European Organization for Research and Treatment of Cancer Core Scale C30 were significantly higher than before treatment (all P<0.05), and the increase was more significant in the observation group (all P<0.05). The median progression free survival and median overall survival in the observation group were 5.9 months and 13.1 months, respectively, significantly longer than those in the control group (4.5 months and 9.6 months) (all P<0.05). During the treatment period, both groups experienced varying degrees of adverse reactions such as hypertension, leukopenia, thrombocytopenia, and liver and kidney damage, but both were mainly grade Ⅰ-Ⅱ. The overall adverse reactions were clinically controllable and tolerable by patients. The incidence of hypertension, thrombocytopenia, hand foot syndrome, and oral ulcers in the observation group was significantly higher than that in the control group (all P<0.05). Conclusions:The combination of apatinib and tirezizumab can effectively regulate the levels of peripheral blood tumor markers and angiogenic regulatory factors in advanced gastric cancer patients who have failed first-line chemotherapy, improve short-term anti-tumor efficacy, and bring more survival benefits to patients.

Objective To analyze the daily quality assurance(QA)measurement results of IBA Sphinx Compact device on the Mevion compact pencil beam scanning proton therapy system for evaluating its clinical application value in proton therapy.Methods The daily QA measurement of Mevion S250i proton therapy system was carried out with Sphinx Compact device for 30 consecutive days,and the measurement results were analyzed.Results The average deviation between the positioning laser and the image center was(0.42±0.27)mm in 30 days.All of the proximal and distal depth errors of the high-and low-energy pencil beams were within 0.50 mm.The position deviation of all the spots measured did not exceed 1.00 mm,and the size deviation was less than 7.5%.The deviation between the image center and the beam center was not more than 0.75 mm.The relative deviation of the flatness of the rectangular field was about 0.5%.The deviation of the output dose of the square field was within 1.0%.Conclusion The proton system daily QA measurement items recommended by AAPM TG-224 report can be accurately and rapidly measured with Sphinx Compact device.The device is a practical and efficient daily QA tool with high practical value in clinic.

Objective To explore the mechanism by which Sestrin2(SESN2)regulates autophagy activity of chondrocytes by mediating mammalian rapamycin target protein complex 1(mTORC1)signaling pathway.Methods The normal chondrocytes were treated with interleukin-1 β(IL-1β)to establish an osteoarthritis(OA)chondrocyte model,which was divided into the control group and the IL-1 β-treated group.Real-time quantitative PCR(qPCR)and Western blot were used to detect the expression levels of matrix metalloproteinase 13(MMP13),type Ⅱ collagen(COL2A1)and SESN2 in the two groups.The cell models of the chondrocyte overexpression SESN2 group and knockdown SESN2 group were obtained via cell transfection technology,and the expression levels of SESN2 in each group were detected by qPCR while those of SESN2,MMP13,COL2A1,mTORC1 pathway-related proteins and autophagy-related proteins in each group were detected by Western blot.The effects of SESN2 on cell proliferation and migration were detected by CCK-8 and cell scratch assay.Results(1)The expression level of MMP13 in the IL-1 β-treated group was significantly up-regulated,while the expression levels of COL2A1 and SESN2 were significantly decreased.(2)Compared with the control group,the expressions of p-mTORC1,ribosomal protein S6 kinase 1(S6K1),and MMP13 protein in OA chondrocytes in the overexpression group were significantly down-regulated,while the expressions of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)and chondroprotective gene COL2A1 were significantly increased,and the expression level of Beclin-1 and the ratio of microtubule associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)/(LC3-Ⅰ)were increased.Meanwhile,overexpression of SESN2 could up-regulate the proliferation and migration of chondrocytes,but the results were opposite after knockdown of SESN2.Conclusion SESN2 can enhance autophagy,proliferation and migration of chondrocytes by inhibiting mTORC1 pathway,which has provided data for revealing the pathogenesis of OA and exploring new therapeutic methods.

Objective:This study aimed to develop a rapid and accurate integrated nucleic acid detection method tailored for the influenza virus.Methods:We designed primers and probes targeting the predominant influenza virus strains circulating in China in recent years. These were integrated with extraction and amplification reagents and a point of care testing (POCT) system to facilitate a seamless and expedited process involving nucleic acid extraction, reaction system preparation, amplification, and result interpretation for the influenza virus. The specificity of the POCT system was evaluated using cultured influenza viruses, while its cross-reactivity was assessed against common respiratory pathogens, including adenovirus and respiratory syncytial virus.Results:Our study successfully developed duplex amplification primers and probes for both influenza A and B viruses, achieving a detection threshold as low as 500 copies/ml. Specificity tests confirmed that the detection reagents did not show cross-reactivity with other respiratory pathogens such as adenovirus and respiratory syncytial virus. The POCT-based rapid nucleic acid detection method for influenza virus was established, it is capable of completing the entire process from nucleic acid extraction to amplification and result interpretation within 50 minutes, while enabling real-time data upload.Conclusions:The POCT-based rapid influenza virus detection kit developed in this study offers a " sample in, results out" convenience, making it suitable for rapid influenza virus detection in primary care settings. This innovation has significant potential for clinical application.

Objective To investigate the changes and clinical significance of plasminogen activator inhibi-tor-1(PAI-1),transforming growth factor-β(TGF-β),vascular endothelial growth factor(VEGF),and inter-leukin-6(IL-6)in patients with tuberculous pleurisy and pleural fibrosis.Methods A total of 103 patients with tuberculous pleurisy and pleural fibrosis who were treated in a hospital from July 2020 to July 2023 were selected as the research subjects.After 2 weeks of treatment,they were divided into a significant effect group and a non-significant effect group based on the therapeutic efficacy of glucocorticoid treatment.The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion were compared before treatment,after 1 and 2 weeks of treatment.The correlation between the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion and the therapeutic efficacy was analyzed by Spearman correlation analysis.Pearson correlation analy-sis was used to analyze the correlation between the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleu-ral effusion and the levels of these indicators in pleural effusion after 2 weeks of treatment.A receiver operat-ing characteristic curve was drawn to analyze the predictive value of the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion for the efficacy of tuberculous pleurisy and pleural fibrosis patients after 1 and 2 weeks of treatment.Results The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 1 and 2 weeks of treatment in both groups were lower than those before treatment,and the levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 1 and 2 weeks of treatment in the significant effect group were lower than those in the non-significant effect group,with statistically significant differences(P＜0.05).The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 1 and 2 weeks of treatment were negatively correlated with the efficacy(P＜0.05).The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion after 2 weeks of treatment were positively correlated(r=0.761,0.783,0.812,0.741,all P＜0.05).The area under the curve(AUC)of combined detection of serum and pleural effusion in-dicators after 1 and 2 weeks of treatment was greater than the AUC of individual indicators(P＜0.05).Con-clusion The levels of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion of patients with tubercu-lous pleurisy and pleural fibrosis are related to the efficacy of treatment.The combined detection of PAI-1,TGF-β,VEGF,and IL-6 in serum and pleural effusion has good predictive value and can provide reference for clinical intervention.

Objective Cervical disc herniation(CDH)is one of the common orthopaedic diseases.With the in-depth study of it and the development of cervical implants,the establishment of cervical fusion animal models has become an indispensable part.Notably however,studies of the establishment and evaluation of cervical fusion animal models in China are currently lacking.This study aimed to provide a suitable animal model and evaluation scheme for implants for cervical spine-related research.Methods Small-tailed Han sheep were chosen for anterior cervical discectomy fusion(ACDF)after modified surgery,and a polyetheretherketone(PEEK)interbody fusion cage(Cage)(control group),3D-printed Ti6Al4V Cage(group 1),and new method Ti6Al4V Cage(group 2)were implanted in different cervical segments(C2/3～C4/5)in each sheep,respectively.Hematology and histopathological analyses were carried out after surgery to evaluate recovery of sheep and the biosafety of the materials.Bone in-growth and bone fusion were assessed by X-ray,computed tomography(CT),Micro-CT and quantitative analysis,hard tissue section staining,and biomechanical tests.Results The modified ACDF ovine model was established successfully.There were no significant differences in important hematology indexes(P＞0.05)and histopathological analysis showed no pathological changes,such as inflammatory cell infiltration.The implants had good biosafety.Furthermore,X-ray and CT examinations showed that the position of internal fixation and the interbody fusion were good.Micro-CT and quantitative analysis at 3 and 6 months after operation showed that compared with PEEK Cage group,the bone volume/total volume and trabecular number were significantly increased(P＜0.01)while the trabecular spacing was significantly decreased in the new method Ti6Al4V and 3D-printed Ti6Al4V groups compared with the PEEK Cage group(P＜0.01).Moreover,the new method new method Ti6Al4V Cage group had more bone growth(P＜0.01).Hard tissue section staining demonstrated that the pores of the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage had obvious bone growth and relatively dense pores in the new method Ti6Al4V and 3D-printed Ti6Al4V groups,and the combination was slightly better than that of PEEK Cage.Biomechanical evaluation indicated that the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage reduced the range of cervical flexion-extension,lateral bending,and axial rotation(P＜0.05)compared with the PEEK cage,as well as enhancing the stability of the cervical vertebra,and the new method Ti6Al4 V Cage was more advantageous(P＜0.05).Conclusions After the establishment of the modified ACDF ovine model,reasonable and effective assessment method were used to demonstrate the suitability and effectiveness of the model and the good biosecurity of all three Cage materials.Compared with the PEEK Cage,the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cages showed better performances in terms of bone growth and bone fusion,which could enhance the stability of the cervical vertebrae.The new method Ti6Al4V Cage was particularly advantageous.

Lumbar spinal stenosis(LSS) is a common degenerative spinal disease. Over the past 30 years, under the concept of minimally invasive spine surgery (MISS), spinal endoscopy has seen significant advancements, particularly in endoscopic unilateral laminotomy for bilateral decompression (ULBD). This technique, utilizing a fluid medium and small incision, achieves spinal canal decompression while maintaining spinal stability, resulting in satisfactory clinical outcomes. However, endoscopic spinal decompression surgery still has some complications, such as nerve injury, dural tears, myeloid hypertension, and epidural hematomas. Some scholars have begun exploring robotic endoscopic spinal surgery to reduce complications and improve clinical outcomes. This article provides an overview of the current state of endoscopic treatment for LSS, aiming to equip surgeons with a comprehensive understanding of this surgical approach to deliver better patient care.