Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form"， this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells （BMSCs） by mediating peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and peroxisome proliferators-activated receptor γ （PPARγ）， providing theoretical support for the prevention and treatment of postmenopausal osteoporosis （PMOP） using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group， Zuogui Wan （ZGW） group， Yougui Wan （YGW） group， and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide （MTT） method， and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ， CCAAT/enharcer-binding protein （C/EBP）α， C/EBPβ， lipoprotein lipase （LPL） protein， brown adipose tissue-related （BAT） proteins PGC-1α， uncoupcing protein 1 （UCP1）， PR domdin-containing protein 16 （PRDM16）， mitochondrial biogenesis-related PGC-1α， nuclear respiratory factor 1 （Nrf1）， nuclear factor E₂-related factor 2 （Nrf2）， and mitochondrial transcription factor A （TFAM）. The expression of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， LPL genes， and the copy number of cytochrome B （CytoB mtDNA） gene was detected using real-time polymerase chain reaction （Real-time PCR）. Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group， the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed， and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， and LPL were significantly downregulated （P<0.01）， while those of the BAT-related factors PGC-1α， UCP1， PRDM16 were significantly upregulated （P<0.01）. The number of mitochondria increased， accompanied by reduced swelling. The double membrane and cristae structure were clear， and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased （P<0.01）. The protein expression levels of mitochondrial biogenesis-related PGC-1α， Nrf1， Nrf2， and TFAM in each treatment group were significantly increased （P<0.01）. ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Peroxisome proliferator-activated receptor gamma(PPAR-γ)is a member of the ligand-activated nuclear tran-scription factor superfamily.Activated PPAR-γ is involved in the regulation of many central nervous system(CNS)events,and is involved in cholesterol metabolism by inducing or inhibi-ting a series of gene pathways,thereby inhibiting the deposition of β-amyloid protein(Aβ).It plays an important neuroprotec-tive role in Alzheimer's disease(AD),improves memory and cognition in AD,and is a potential target for AD.Drug develop-ment aimed at restoring cholesterol homeostasis may be a poten-tial strategy to counteract AD.By analyzing the distribution and structure of PPAR-γ,focusing on the biological correlation be-tween PPAR-γ-mediated cholesterol metabolism and AD,this paper describes the mechanism regulation of PPAR-γ on key proteins,genes and their corresponding molecules,providing a new reference for the treatment of AD.

Aim To construct a DC-targeted modified(lacto-N-fucop-entose Ⅲ,LewisX)Pseudomonas aeruginosa(PA)DNA vaccine PLGA nanoparticle(LewisX-PLGA)loading PA PcrV and OprF genes combination,and provide a new idea for the prevention of PA clinical infection.Methods The PLGA nano-particles loading PA PcrV and OprF combined DNA(PLGA+PcrV/OprF)or loading pEGFP(PLGA+pEGFP)were pre-pared by double emulsification-solvent evaporation method.On this basis,the DC-SIGN-targeted ligand LewisX was connected to the surface of PLGA nanoparticles by amide condensation reac-tion.LewisX-modified PLGA-PcrV/OprF(LewisX-PLGA+PcrV/OprF)and LewisX-modified PLGA-pEGFP(LewisX-PL-GA+pEGFP)were prepared.Particle size,Zeta potential,en-capsulation rate and drug loading were evaluated to characterize LewisX-PLGA+PcrV/OprF.The cytotoxicity of LewisX-PLGA+PcrV/OprF was investigated by CCK-8.DC targeting of LewisX-PLGA+pEGFP was validated in vitro transfection.Further,LewisX-PLGA+PcrV/OprF lysosome escape was used to evalu-ate the targeting performance of LewisX-modified PLGA nanopar-ticles loading DNA in vitro.The immunoefficacy of the nanopar-ticles was evaluated by detecting the level of lymphocyte prolifer-ation,humoral immunity and immune protection.Results The diameter of LewisX-PLGA+PcrV/OprF was(201.17±1.6)nm.The encapsulation efficiency of LewisX-PLGA+PcrV/OprF was(85.72±5.3)％.The Zeta potential of LewisX-PLGA+PcrV/OprF was+(31.17±1.8)mV.In the DC2.4 cytotoxici-ty test,the cell survival rates were above 85％.The results of fluorescence microscopy after LewisX-PLGA+pEGFP transfec-tion in vitro showed that LewisX-PLGA+pEGFP was more readi-ly taken up by DC2.4,and LewisX-PLGA+pEGFP had a DC-SIGN specific targeting performance.The CLSM's observation of LewisX-PLGA+Pcrv/OprF showed that more DNA escaped from the lysosome into the cytoplasm.The results suggested that LewisX-PLGA had DC2.4 targeting performance.Because DC2.4 cells endocyted more LewisX-PLGA+Pcrv/OprF into the lysosome,the amount of DNA carried by the nanoparticles esca-ping into the cytoplasm increased.in vivo immune results showed that the lymphocyte proliferation level and antibody titer level of targeted DNA vaccine increased significantly,further improved the survival rate of mice infected with acute pneumoni-a,and reduced the bacterial load of mouse lungs.Conclusions The DC-SIGN-targeted aptamer-modified PA DNA vaccine nanoparticle LewisX-PLGA can be successfully constructed.It promotes the transfection of DNA into DC.It promotes the endo-cytosis of PA DNA vaccine into the DC lysosome and the escape of PA DNA into the cytoplasm.This results in a significant im-mune response in body,which enhances the protective efficacy of vaccine.

Objective To investigate the effect of Polyetheretherketone(PEEK)rod semi-rigid pedicle screw fixation sys-tem in lumbar spine non-fusion surgery.Methods A total of 74 patients with tow-level lumbar degenerative diseases who un-derwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group.In the PEEK rod group,there were 34 patients,including 13 males and 21 females,aged from 51 to 79 years old with an average of(62.4±6.8)years old;There were 1 patient of L1-L3 segments,7 patients of L2-L4 segments,20 patients of L3-L5 segments and 6 pa-tients of L4-S1 segments.In the titanium rod group,there were 40 patients,including 17 males and 23 females,aged from 52 to 81 years old with an average of(65.2±7.3)years old;There were 3 patient of L1-L3 segments,11 patients of L2-L4 segments,19 patients of L3-L5 segments and 7 patients of L4-S1 segments.The general conditions of operation,such as operation time,intraoperative blood loss,postoperative drainage was recorded.The visual analogue scale(VAS)for low back pain and Os-westry disability index(ODI)were compared in preoperatively and postoperatively(3 months,12 months and last follow-up)between two groups.The change of range of motion(ROM)was observed by flexion and extension x-ray of lumbar Results All patients successfully completed the operation.The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6)months.The operative time(142.2±44.7)min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group[(160.7±57.3)min、(212.8±85.4)ml](P＜0.05).There was no significant differences in postoperative drainage between the two groups(P＞0.05).At the final follow-up visit,in PEEK group and titanium group VAS of low back pain[(0.8±0.4)points vs(1.0±0.5)points],VAS for leg pain[(0.7±0.4)points vs(0.8±0.5)points]and ODI[(9.8±1.6)％vs(12.1±1.5)％]were compared with preoperative[(5.8±1.1)points vs(6.0±1.1)points],[(7.2±1.7)points vs(7.0±1.6)points],[(68.5±8.9)％vs(66.3±8.2)％]were significantly different(P＜0.05).There was no significant difference in VAS scores between the two groups at each postoperative time point(P＞0.05).At 3 months after surgery,there was no difference in ODI between the two groups(P＞0.05).There were significant differences in ODI between PEEK group and titanium rod group at 12 months[(15.5±2.1)％vs(18.4±2.4)％]and at the last follow-up[(9.8±1.6)％vs(12.1±1.5)％](P＜0.05).The total range of motion(ROM)of lumbar decreased in both groups after surgery.At 12 months after surgery and the last follow-up,the PEEK group compared with the titanium rod group,the total range of motion of lumbar was statistically significant(P＜0.05).The range of motion(ROM)of the fixed segments decreased in both groups after surgery.The ROM of the fixed segments in PEEK group decreased from(9.5±4.6)° to(4.1±1.9)° at the last follow-up(P＜0.05),which in the titanium rod group was de-creased from(9.8±4.3)°to(0.9±0.5)° at the last follow-up(P＜0.05).The range of motion(ROM)of upper adjacent segment increased in both groups,there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up,(P＜0.05).There was no screw loosening and broken rods in both groups during the follow-up period.Conclusion The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment,showing comparable short-term clinical efficacy to titanium rod fu-sion.PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degener-ative diseases,and its long-term efficacy needs further follow-up observation.