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.

BACKGROUND:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.

OBJECTIVE: To explore the effectiveness of primary interventional revascularization combined with secondary perforator composite flap in the treatment of peripheral arterial disease (PAD) accompanied by soft tissue defects around the ankle. METHODS: Between January 2022 and January 2025, 12 patients with PAD and soft tissue defects around the ankle were admitted. Among them, there were 9 males and 3 females; their ages ranged from 52 to 82 years, with an average of 68.9 years. The causes of injury included 4 cases of traffic accident, 5 cases of falls, 1 case of falling from height, 1 case of foreign body puncture injury, and 1 case of electric shock injury. The infection duration ranged from 1 month to 35 years, with a median duration of 3.5 months. The wound size ranged from 5.5 cm×3.0 cm to 15.0 cm×9.0 cm. The ankle-brachial index (ABI) was 0.32±0.12. The visual analogue scale (VAS) score for pain was 3.3±0.5. Preoperative vascular stenosis assessment was performed in all patients, with primary intervention to dredge large and medium-sized arteries, followed by secondary repair of the wound using a perforator composite flap. The flap size ranged from 6.5 cm×4.0 cm to 16.0 cm×10.0 cm. The donor sites were sutured directly or repaired with skin grafts. After two stages of treatment, the effectiveness was evaluated by measuring ABI, observing flap survival and wound healing, assessing VAS scores, and American Orthopedic Foot and Ankle Society (AOFAS) scores. RESULTS: All 12 cases completed two stages of treatment; all patients were followed up after the second-stage treatment, with a follow-up period ranging from 7 to 28 months, with an average of 16.8 months. After the first-stage treatment, the skin temperature around the ankle was significantly higher than that before treatment, and the ABI increased to 0.71±0.07, with a significant difference ( t=9.918, P<0.001). After the second-stage treatment, the blisters on the distal end of the skin flap occurred in 3 cases. The flaps survived and the wounds healed, with a healing time ranging from 10 to 14 days (mean, 11.8 days). The incisions at the donor site healed by first intention, and the skin grafts survived. The VAS score was 0.5±0.5 at 3 weeks, which was significantly lower than that before treatment ( t=13.675, P<0.001). No infection recurrence occurred during follow-up. At 6 months after the second-stage treatment, the AOFAS score of the ankle joint ranged from 92 to 97, with an average of 94.7, all reaching excellent. CONCLUSION Interventional revascularization combined with perforator composite flap for staged treatment of PAD with ankle soft tissue defects can obtain good effectiveness, by unclogging the main blood vessels, improving lower limb blood supply, and improving the survival rate of the skin flap.
Humans ; Male ; Female ; Middle Aged ; Aged ; Peripheral Arterial Disease/surgery* ; Soft Tissue Injuries/surgery* ; Perforator Flap/blood supply* ; Plastic Surgery Procedures/methods* ; Aged, 80 and over ; Ankle/blood supply* ; Treatment Outcome ; Ankle Brachial Index ; Skin Transplantation/methods*

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 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.

Objective:To verify and calibrate the CT modeling curves of three CT devices in RayStation proton treatment planning system (TPS).Methods:CT-mass density (CT-MD) curves were established by CT Hounsfield units of different tissue substitute materials obtained by scanning the model with CT equipment. CT-stopping power (CT-SP) curves were established by calculation based on the chemical composition of various human tissues. The equivalent water thickness of tissue substitute modules was calculated with different CT modeling curves in TPS. The actual equivalent water thickness of various modules was measured by a Bragg peak detector, and compared with the calculated values of TPS to verify the accuracy of different CT models.Results:The differences of CT modeling curves were significantly different under different tube voltage scanning protocols. Compared with CT-MD curves, CT-SP curves based on the stoichiometric calibration were more suitable for proton dose calculation. However, the values of stopping power corresponding to high CT values still needed to be optimized, and the calculation error after calibration was less than 3%.Conclusion:The method of verifying and calibrating CT unit curves of proton TPS is described, proving that the CT-SP curves after stoichiometric calculation are more suitable for proton dose calculation.

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 value of dual-energy CT(DECT)quantitative parameters combined with clinical laboratory indicators in differentiation of portal vein tumor thrombus(PVTT)from thrombosis(PVT).Methods A case-control study was conducted on 65 patients diagnosed with portal vein thrombosis(n=39)or tumor embolus(n=26)who underwent abdominal dual-energy enhanced CT examination in our department from May 2022 to March 2024.Their clinical and imaging data were collected.Linear blending image(LB),non-linear blending image(NLB),40 keV and 100 keV virtual monoenergetic image(VMI),iodine image and electron density/effective atomic number image(Rho/Zeff)were reconstructed with the aid of post-processing workstation.The image characteristics of thrombus were evaluated in LB images,including whether the vessel wall at the thrombus was smooth,whether the vessel at the thrombus was widen,and whether the embolus was neovascularization.The quantitative parameters and clinical laboratory indicators of PVT and PVTT in DECT were compared.Laboratory indicators included apha-fetoprotein(AFP),carcinoembryonic antigen(CEA),alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Univariate and multivariate logistic regression analyses were employed to analyze DECT quantitative parameters,embolus image characteristics and clinical laboratory indicators.Then receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic efficiency of the quantitative parameters and combined model of DECT.Results Among the DECT parameters,except for Rho,the other parameters in PVTT were significantly higher than those in PVT(P＜0.05).Multivariate logistic regression analysis showed that there were obvious differences in LB,NLB,CEA and AST(P＜0.05),and NLB had better diagnostic efficacy(AUC:0.830,sensitivity:53.85％,specificity:100.00％,accuracy:81.54％).The combined model based on DECT quantitative parameters and clinical laboratory indicators(LB+NLB+CEA+AST)obtained the best diagnostic efficacy(AUC:0.983,sensitivity:96.15％,specificity:92.31％,accuracy:93.85％).Conclusion The combined imaging and clinical model based on DECT provides a reliable reference for the differential diagnosis of benign and malignant portal vein embolus,and it has potential application prospects.