Objective:To investigate alterations in brain function among elderly patients with interstitial cystitis/bladder pain syndrome(IC/BPS)during the resting state.Methods:We prospectively recruited seven elderly patients with IC/BPS admitted to the Urology Department of Beijing Hospital from December 2023 to May 2024 as the experimental group, and concurrently selected twelve elderly healthy individuals as the control group.After enrollment, all participants underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans.General clinical data, including age and gender, as well as standardized assessment scores from the Interstitial Cystitis Symptom Index(ICSI), Interstitial Cystitis Problem Index(ICPI), Visual Analogue Scale(VAS), Self-Rating Anxiety Scale(SAS), and Self-Rating Depression Scale(SDS), were collected.The data were processed using Matlab.This study employed a paired sample t-test to analyze the differences in gray matter volume between the two groups.The functional activities of the subjects' brains were analyzed using regional homogeneity(ReHo)and low-frequency amplitude(ALFF)algorithms.Based on the identified abnormal brain regions, further functional connectivity(FC)analysis was conducted to explore the connectivity patterns among the functional brain regions.Results:No significant differences were observed in age( t=-0.68, P=0.536)or gender( χ2=0.019, P=0.891)between the experimental group and the control group.The scores of SAS and SDS in the experimental group were significantly higher than those in the control group( P<0.001).No significant difference was observed in cerebral gray matter volume between the two subject groups.In contrast to the control group, the ALFF value of the left superior parietal lobe(MNI: x, y, z=-21, -66, 60; t=12.530 5)was elevated in elderly patients with IC/BPS, and the ReHo value of the left precuneus(MNI: x, y, z=-9, -54, 63; t=9.410 3)was also increased.Through FC analysis, it was revealed that elderly IC/BPS patients exhibited significantly lower FC values between the left superior parietal lobule and the central sulcus(MNI: x, y, z=21, 15, 3; t=-27.835 6), as well as between the left anterior cingulate and the left posterior cingulate gyrus(MNI: x, y, z=-12, 0, 42; t=-8.738 9)in comparison with the control group. Conclusions:In contrast to normal individuals, elderly IC/BPS patients demonstrate functional aberrations in the left superior parietal lobule and the left precuneus.Moreover, a decrease in functional connectivity is observed between the left superior parietal lobule and the central sulcus, as well as between the left precuneus and the left posterior cingulate gyrus.These abnormal functional alterations in the brain may be implicated in the maintenance and development of symptoms in IC/BPS patients.This study conducted research from the perspective of central nervous system regulation, presenting possible directions for further exploration of the pathophysiological mechanisms of IC/BPS.

Acupotomy therapy demonstrates the definite clinical efficacy on knee osteoarthritis (KOA). After reviewing systematically the mechanism studies on acupotomy for KOA over the past 5 years, It is revealed that acupotomy synergistically intervenes in the pathological progression of KOA through multi-target approaches, such as regulating cartilage homeostasis, restoring skeletal muscle function, alleviating synovial inflammatory responses, remodeling subchondral bone, and neuromodulation. But the current research still limits to single-tissue phenotypic observation, and is insufficiency in the in-depth exploration of multi-tissue synergistic interactions and molecular upstream-downstream regulatory mechanisms. Future studies should focus on the inheritance and innovation of acupotomy theory, and integrating multi-omics analytical technologies, artificial intelligence, and novel biochemical detection methods. The mechanism research targets on the interaction mechanisms among tissues, direct effects of acupotomy, immune-inflammatory regulatory mechanisms, and analgesic mechanisms, so as to comprehensively elucidate the therapeutic mechanism of acupotomy for KOA.
Humans ; Acupuncture Therapy ; Osteoarthritis, Knee/genetics* ; Animals

Objective:To explore the effects of anshen jieyu decoction on hippocampal morphology and regulation of PI3K/AKT signalling pathway with hypothalamic-pituitary-adrenal axis expression in CUMS depressed rats.Methods:Rats were divided into a control group(Control),CUMS model group(CUMS),and ASJYD treatment group(CUMS+ASJYD).Rats in the CUMS and CUMS+ASJYD groups were exposed to 10 different chronic stressors to induce depressive-like behaviors.After modeling,the CUMS+ASJYD group received ASJYD via gavage.Depressive-like behaviors were assessed using the sucrose preference test and open field test.Serum levels of adrenocorticotropic hor-mone(ACTH)and corticosterone(CORT)were measured by ELISA.Hippocampal neuronal morphological changes were observed via Nissl staining,mitochondrial ultrastructure was examined using transmission electron microscopy,and hippocampal PI3K and AKT protein phosphorylation levels were detected by Western blot.Results:Compared with the Control group,the CUMS group showed significantly reduced sucrose consumption,preference rate,total travel distance in the open field,and central zone activity time(P＜0.01).Serum ACTH and CORT levels were elevated(P＜0.01),with disorganized hippocampal cell arrangement,reduced cell count,mitochondrial swelling,cristae blurring/rupture observed under electron microscopy,and decreased phosphorylation levels of PI3 K and AKT proteins(P＜0.01).After ASJYD treatment,the CUMS+ASJYD group exhibited significant improvements in sucrose consumption,preference rate,locomotor activity,and central zone exploration(P＜0.01),accompanied by reduced ACTH/CORT expression,alleviated hippocampal pathology,restored mitochondrial integrity with clear cristae,and increased PI3K/AKT phosphorylation(P＜0.01).Conclusion:Anshen Jieyu decoction significantly improved the depression-like be-haviour of CUMS rats,which may be achieved by down-regulating the hyperactive hypothalamic-pituitary-adrenal axis,regulating the expression of PI3K/AKT signaling pathway,and ameliorating the damage to hippocampal neurons and mi-tochondria.

Objective:To explore the effects of anshen jieyu decoction on hippocampal morphology and regulation of PI3K/AKT signalling pathway with hypothalamic-pituitary-adrenal axis expression in CUMS depressed rats.Methods:Rats were divided into a control group(Control),CUMS model group(CUMS),and ASJYD treatment group(CUMS+ASJYD).Rats in the CUMS and CUMS+ASJYD groups were exposed to 10 different chronic stressors to induce depressive-like behaviors.After modeling,the CUMS+ASJYD group received ASJYD via gavage.Depressive-like behaviors were assessed using the sucrose preference test and open field test.Serum levels of adrenocorticotropic hor-mone(ACTH)and corticosterone(CORT)were measured by ELISA.Hippocampal neuronal morphological changes were observed via Nissl staining,mitochondrial ultrastructure was examined using transmission electron microscopy,and hippocampal PI3K and AKT protein phosphorylation levels were detected by Western blot.Results:Compared with the Control group,the CUMS group showed significantly reduced sucrose consumption,preference rate,total travel distance in the open field,and central zone activity time(P＜0.01).Serum ACTH and CORT levels were elevated(P＜0.01),with disorganized hippocampal cell arrangement,reduced cell count,mitochondrial swelling,cristae blurring/rupture observed under electron microscopy,and decreased phosphorylation levels of PI3 K and AKT proteins(P＜0.01).After ASJYD treatment,the CUMS+ASJYD group exhibited significant improvements in sucrose consumption,preference rate,locomotor activity,and central zone exploration(P＜0.01),accompanied by reduced ACTH/CORT expression,alleviated hippocampal pathology,restored mitochondrial integrity with clear cristae,and increased PI3K/AKT phosphorylation(P＜0.01).Conclusion:Anshen Jieyu decoction significantly improved the depression-like be-haviour of CUMS rats,which may be achieved by down-regulating the hyperactive hypothalamic-pituitary-adrenal axis,regulating the expression of PI3K/AKT signaling pathway,and ameliorating the damage to hippocampal neurons and mi-tochondria.

Objective·To construct an interpenetrating network hydrogel(HMGL)that can induce hypoxia in situ,investigate its effects on promoting the secretion of extracellular matrix in nucleus pulposus cells(NPCs),and evaluate its potential in the treatment of intervertebral disc degeneration.Methods·HMGLs capable of long-term in situ hypoxia induction were prepared by a two-step polymerization method.Hypoxic hydrogels with laccase concentrations of 5 U/mL and 10 U/mL,namely HMGL-5 and HMGL-10,were constructed,whereas a hyaluronic acid methacryloyl(HAMA)hydrogel served as the control.The molecular structures of HAMA and gelatin grafted with vanillin(GelVA)were verified by 1H nuclear magnetic resonance spectra(1H NMR)and Fourier transform infrared spectroscopy(FTIR).The microstructures of the hydrogels were observed by scanning electron microscope(SEM),and the mechanical properties of the hydrogels were tested by a rotational rheometer and a dynamic mechanical analyzer(DMA).The induced hypoxic behaviors of the hydrogels were detected by an oxygen consumption fluorescent probe.The biocompatibility of the hydrogels was tested by live/dead staining and the cell counting kit 8(CCK-8)assay,and the expression of hypoxia-inducible factor-1α(HIF-1α)and type Ⅱ collagen(Col Ⅱ)in NPCs was detected by immunofluorescence staining.A rat model of intervertebral disc degeneration was established,and hydrogels loaded with NPCs were injected into degenerated intervertebral discs to evaluate their repair effects.Disc height and disc water content changes were detected by X-ray imaging and magnetic resonance imaging(MRI),and the integrity of disc structure and proteoglycan levels were detected by histological staining.Results·Structural characterization demonstrated that the materials had been successfully prepared.SEM showed that the three hydrogels all had a loose and porous structure,and their elastic moduli increased with the decrease of pore size.Hypoxia test results indicated that the hypoxia-inducing ability of HMGL-10 hydrogel was the strongest.In vitro experimental results showed that the three hydrogels all had good biocompatibility.Compared with the HAMA hydrogel,the HIF-1α of NPCs was significantly activated in the HMGL-10 hydrogel.The expression levels of HIF-1α and Col Ⅱ in the HMGL-10 hydrogel group were 3.38 and 4.15 times higher than those in the HAMA hydrogel group.In vivo experimental results showed that the integrity,height,and water content of the intervertebral discs in the hypoxia hydrogel group were all superior to those in the other treatment groups.Conclusion·The in situ hypoxia-inducing hydrogel effectively activates HIF-1α,promotes extracellular matrix secretion,and demonstrates superior regenerative potential for intervertebral disc repair.

Objective·To construct an interpenetrating network hydrogel(HMGL)that can induce hypoxia in situ,investigate its effects on promoting the secretion of extracellular matrix in nucleus pulposus cells(NPCs),and evaluate its potential in the treatment of intervertebral disc degeneration.Methods·HMGLs capable of long-term in situ hypoxia induction were prepared by a two-step polymerization method.Hypoxic hydrogels with laccase concentrations of 5 U/mL and 10 U/mL,namely HMGL-5 and HMGL-10,were constructed,whereas a hyaluronic acid methacryloyl(HAMA)hydrogel served as the control.The molecular structures of HAMA and gelatin grafted with vanillin(GelVA)were verified by 1H nuclear magnetic resonance spectra(1H NMR)and Fourier transform infrared spectroscopy(FTIR).The microstructures of the hydrogels were observed by scanning electron microscope(SEM),and the mechanical properties of the hydrogels were tested by a rotational rheometer and a dynamic mechanical analyzer(DMA).The induced hypoxic behaviors of the hydrogels were detected by an oxygen consumption fluorescent probe.The biocompatibility of the hydrogels was tested by live/dead staining and the cell counting kit 8(CCK-8)assay,and the expression of hypoxia-inducible factor-1α(HIF-1α)and type Ⅱ collagen(Col Ⅱ)in NPCs was detected by immunofluorescence staining.A rat model of intervertebral disc degeneration was established,and hydrogels loaded with NPCs were injected into degenerated intervertebral discs to evaluate their repair effects.Disc height and disc water content changes were detected by X-ray imaging and magnetic resonance imaging(MRI),and the integrity of disc structure and proteoglycan levels were detected by histological staining.Results·Structural characterization demonstrated that the materials had been successfully prepared.SEM showed that the three hydrogels all had a loose and porous structure,and their elastic moduli increased with the decrease of pore size.Hypoxia test results indicated that the hypoxia-inducing ability of HMGL-10 hydrogel was the strongest.In vitro experimental results showed that the three hydrogels all had good biocompatibility.Compared with the HAMA hydrogel,the HIF-1α of NPCs was significantly activated in the HMGL-10 hydrogel.The expression levels of HIF-1α and Col Ⅱ in the HMGL-10 hydrogel group were 3.38 and 4.15 times higher than those in the HAMA hydrogel group.In vivo experimental results showed that the integrity,height,and water content of the intervertebral discs in the hypoxia hydrogel group were all superior to those in the other treatment groups.Conclusion·The in situ hypoxia-inducing hydrogel effectively activates HIF-1α,promotes extracellular matrix secretion,and demonstrates superior regenerative potential for intervertebral disc repair.

Objective:To investigate alterations in brain function among elderly patients with interstitial cystitis/bladder pain syndrome(IC/BPS)during the resting state.Methods:We prospectively recruited seven elderly patients with IC/BPS admitted to the Urology Department of Beijing Hospital from December 2023 to May 2024 as the experimental group, and concurrently selected twelve elderly healthy individuals as the control group.After enrollment, all participants underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans.General clinical data, including age and gender, as well as standardized assessment scores from the Interstitial Cystitis Symptom Index(ICSI), Interstitial Cystitis Problem Index(ICPI), Visual Analogue Scale(VAS), Self-Rating Anxiety Scale(SAS), and Self-Rating Depression Scale(SDS), were collected.The data were processed using Matlab.This study employed a paired sample t-test to analyze the differences in gray matter volume between the two groups.The functional activities of the subjects' brains were analyzed using regional homogeneity(ReHo)and low-frequency amplitude(ALFF)algorithms.Based on the identified abnormal brain regions, further functional connectivity(FC)analysis was conducted to explore the connectivity patterns among the functional brain regions.Results:No significant differences were observed in age( t=-0.68, P=0.536)or gender( χ2=0.019, P=0.891)between the experimental group and the control group.The scores of SAS and SDS in the experimental group were significantly higher than those in the control group( P<0.001).No significant difference was observed in cerebral gray matter volume between the two subject groups.In contrast to the control group, the ALFF value of the left superior parietal lobe(MNI: x, y, z=-21, -66, 60; t=12.530 5)was elevated in elderly patients with IC/BPS, and the ReHo value of the left precuneus(MNI: x, y, z=-9, -54, 63; t=9.410 3)was also increased.Through FC analysis, it was revealed that elderly IC/BPS patients exhibited significantly lower FC values between the left superior parietal lobule and the central sulcus(MNI: x, y, z=21, 15, 3; t=-27.835 6), as well as between the left anterior cingulate and the left posterior cingulate gyrus(MNI: x, y, z=-12, 0, 42; t=-8.738 9)in comparison with the control group. Conclusions:In contrast to normal individuals, elderly IC/BPS patients demonstrate functional aberrations in the left superior parietal lobule and the left precuneus.Moreover, a decrease in functional connectivity is observed between the left superior parietal lobule and the central sulcus, as well as between the left precuneus and the left posterior cingulate gyrus.These abnormal functional alterations in the brain may be implicated in the maintenance and development of symptoms in IC/BPS patients.This study conducted research from the perspective of central nervous system regulation, presenting possible directions for further exploration of the pathophysiological mechanisms of IC/BPS.

Abstract On 18 May 2021, the Center for Disease Control and Prevention (CDC) of X District in P City, Z Province received a co-investigation of a suspected case of intentional HIV transmission from the public security branch, and conducted epidemiological investigations on Zhao and Wang (both males). Wang was confirmed HIV-positive in 2019. Zhao had unprotected sexual encounters several times with Wang in March 2021 without being informed of Wang's HIV infection. Zhao developed fever, sore throat and other symptoms of acute infection phase on 28 March, and were confirmed HIV positive by the CDC of P City on 11 May. Zhao did not have sex with anyone else before or after having sex with Wang. In addition, Zhao had no history of surgery, blood transfusions, drug use or any other history of HIV exposure. Laboratory tests conducted by the CDC of Z Province showed that the HIV nucleic acid sequences between the samples of Zhao and Wang had a high degree of homology. Combined with the epidemiological investigation, laboratory testing and the evidence from the public security branch, it was concluded that Wang intentionally transmitted HIV to Zhao through unprotected anal sex without disclosing his HIV infection status.

Objective:To screen the interacting protein of ubiquitin-conjugating enzyme E2S(UBE2S)and construct the hepatocellular carcinoma(HCC)based on UBE2S interacting protein prognosis model(UIPM),and to discuss the value of UIPM in assessing the prognosis of the HCC patients.Methods:Co-immunoprecipitation(Co-IP)was used to screen the protein complexes binding to Flag-UBE2S.After validation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting methods;liquid chromatography-mass spectrometer(LC-MS)was used to identify the UBE2S interacting proteins;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted on these proteins;the prognosis-related proteins from The Cancer Genome Atlas(TCGA)were cross-referenced with UBE2S interacting proteins by survival package of R software;the key proteins were extracted through LASSO regression analysis to build the UIPM;the prognostic model risk scoring formula was established.The HCC patients in TCGA were divided into high risk group and low risk group based on median value of the risk scores.The predictive accuracy of UIPM was evaluated by receiver operating characteristic curve(ROC),and the predictive accuracy was further validated by International Cancer Genome Consortium(ICGC)Database;univariate regression analysis and multivariate Cox regression analysis were used to detect whether the UIPM risk score was an independent prognostic factor for HCC.Furthermore,the nomogram model was built.Results:A total of 97 UBE2S interacting proteins were identified through Co-IP combined with LC-MS analysis.The GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the interacting proteins were closely associated with cysteine-type endopeptidase activity,oxidative stress,and cell death.The TCGA revealed 5 163 HCC prognosis-related proteins;after intersecting with UBE2S interacting proteins,40 prognosis-related interacting proteins were found.Seven key proteins were determined through LASSO regression analysis,including UBE2S,heat shock protein family A member 8(HSPA8),heterogeneous nuclear ribonucleoprotein H1(HNRNPH1),chaperonin containing TCP1 subunit 3(CCT3),eukaryotic translation initiation factor 2 subunit 1(EIF2S1),receptor for activated C kinase 1(RACK1),and actin related protein 2/3 complex subunit 4(ARPC4),and the UIPM was constructed.There was significant difference in survival rate of the patients between high risk group and low risk group(P<0.05).The ROC curve analysis results showed the area under ROC curve(AUC)values of UIPM for predicting 1-year,2-year,and 3-year survival risk scores of the HCC patients were all greater than 0.7,indicating the model had high predictive accuracy.This was also confirmed by ICGC Database data.The univariate and multivariate Cox regression analysis results showed that the UIPM risk score was an independent prognostic risk factor for the HCC patients(P<0.05).The nomogram results showed good consistency between predicted survival rate and actual survival rate of the patient.Conclusion:A total of 97 interacting proteins that interact with UBE2S may promote the occurence and devolopment of HCC through oxidative stress and dysregulation of ferroptosis pathways.The UIPM risk score is an independent risk factor for the prognosis of HCC and can be used to predict the outcomes of the patients.UBE2S,HSPA8,HNRNPH1,CCT3,EIF2S1,RACK1,and ARPC4 could be regarded as the new biomarkers and therapeutic targets for HCC.