AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P＜0.05,P＜0.01);prolonged evasion latency(P＜0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P＜0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P＜0.01);decreased levels of M2-type marker CD206(P＜0.05);elevated levels of TNF-α and IL-1β(P＜0.01);decreased expressions of IL-13 and IL-4(P＜0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P＜0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P＜0.05,P＜0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.

AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P＜0.05,P＜0.01);prolonged evasion latency(P＜0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P＜0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P＜0.01);decreased levels of M2-type marker CD206(P＜0.05);elevated levels of TNF-α and IL-1β(P＜0.01);decreased expressions of IL-13 and IL-4(P＜0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P＜0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P＜0.05,P＜0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.

Objective To design an individually portable oral treatment device to solve the problems of oral diagnosis and treatment under field conditions in alpine regions.Methods The individually portable oral treatment device had a trolley box structure and consisted of an outer box,an inner framework and an operation panel.The outer box was made of low-density polyethylene material and formed by by one-time rotational moulding process;the inner framework integrated a plateau com-pressor,an independent negative-pressure compressor,an integrated control system for programmable logic controller(PLC),an individually portable respiratory synchronized pulsed oxygen supply module for plateau application;there were several curative devices equipped in the operation panel,including a 3-way syringe,a high-speed turbine handpiece,an electric variable-speed handpiece,a water control switch,a light curing machine and an ultrasonic dental cleaning handpiece.Trials were carried out with the test-phase prototype in alpine regions so as to verify the performance of the device.Results Trials proved that the prototype gained advantages in mobility,multifunctionality and pressure supply facilitating continuous operation of power gas source for oral diagnosis and treatment in alpine regions.Conclusion The device developed solves the problems in pressure insufficiency and instability,control system integration,portability and oxygen supply for medical staffs,improves the mobility of oral diagnosis and treatment in alpine regions and enhances the oral support service and equipment effectively.[Chinese Medical Equipment Journal,2025,46(1):108-113]

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective:To investigate the efficacy and safety of transurethral water vapor thermal therapy(WVTT)using the Rezūm system for benign prostatic hyperplasia(BPH)in the real world.Methods:A total of 181 patients with BPH were recruited from the Second Affiliated Hospital of Nanjing Medical University from August 2022 to December 2023,of whom 173 patients were treated with WVTT using the Rezūm system,while 8 patients were treated with WVTT combined with TURP.They were followed up at 1,3,and 6 months postoperatively to assess changes in the IPSS,QoL,Qmax,IIEF-5,and the occurrence of any complications.Results:All 181 surgeries in this group were successfully completed.The operation time of the Rezūm system was(4.6±1.4)mi-nutes.The postoperative indwelling catheterization time was(8.0±2.1)days.With a follow-up of at least 6 months,there was a significant decrease in PV,IPSS and QoL,and a remarkable increase had been found in Qmax as well(P＜0.05).There was no sig-nificant difference in IIEF-5 before and after the operation(P＞0.05).In this groups of patients,postoperative complications mainly included 95 cases(52.5％)of gross hematuria,6 cases(3.3％)of retrograde ejaculation,5 cases(2.8％)of urethral stricture,4 cases(2.2％)of prostatitis,and 10 cases(5.5％)of urinary tract infection.Four cases(2.2％)underwent surgical retreatment for BPH after surgery.Conclusion:In the real world,the use of Rezūm thermal steam ablation system for the treatment of BPH has sat-isfactory short-term effect,short surgical time,and significant improvement in IPSS,QoL,Qmax,which does not adversely affect sexu-al function.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective:To evaluate the effects and underlying mechanisms of preoperative intestinal microbiota modulation on the recovery of prolonged postoperative ileus(PPOI)in gastric cancer patients with sarcopenia Methods:Skeletal muscle mass(SMM)was assessed using bioelectrical impedance analysis(BIA),and the skeletal muscle index(SMI)was calculated.A total of 156 gastric cancer patients with sarcopenia who underwent surgery at the Department of Gastrointestinal Surgery,Liyang People's Hospital,from January 2022 to December 2024 were randomly assigned to either the control group or the experimental group.The control group received conventional prehabilitation interventions,including nutritional support,respiratory function training,and physical exercise.The experimental group received probiotic-based intestinal microbiota modulation in addition to conventional prehabilitation interventions.Postoperative recovery indicators,including time to first flatus,incidence of postoperative complications,length of hospital stay,and hospitalization costs,were compared between the two groups.Results:Among the 156 sarcopenic gastric cancer patients,121 were male,and 35 were female.Statistically significant differences were observed between the two groups in terms of time to first flatus,incidence of postoperative complications,and length of hospital stay(P<0.05).Postoperative complications occurred in 38 patients(24.3%),with 10 cases(6.4%)in the experimental group and 28 cases(17.9%)in the control group.The time to first flatus in the experimental group was significantly shorter than in the control group(48.0 hours vs 72.0 hours,P<0.001).Conclusion:Preoperative intestinal microbiota modulation significantly reduces the incidence of PPOI and postoperative complications in gastric cancer patients with low SMI,thereby promoting postoperative gastrointestinal function recovery.

Objective To design an individually portable oral treatment device to solve the problems of oral diagnosis and treatment under field conditions in alpine regions.Methods The individually portable oral treatment device had a trolley box structure and consisted of an outer box,an inner framework and an operation panel.The outer box was made of low-density polyethylene material and formed by by one-time rotational moulding process;the inner framework integrated a plateau com-pressor,an independent negative-pressure compressor,an integrated control system for programmable logic controller(PLC),an individually portable respiratory synchronized pulsed oxygen supply module for plateau application;there were several curative devices equipped in the operation panel,including a 3-way syringe,a high-speed turbine handpiece,an electric variable-speed handpiece,a water control switch,a light curing machine and an ultrasonic dental cleaning handpiece.Trials were carried out with the test-phase prototype in alpine regions so as to verify the performance of the device.Results Trials proved that the prototype gained advantages in mobility,multifunctionality and pressure supply facilitating continuous operation of power gas source for oral diagnosis and treatment in alpine regions.Conclusion The device developed solves the problems in pressure insufficiency and instability,control system integration,portability and oxygen supply for medical staffs,improves the mobility of oral diagnosis and treatment in alpine regions and enhances the oral support service and equipment effectively.[Chinese Medical Equipment Journal,2025,46(1):108-113]

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).