Correlations of brain network functional connectivity alterations with cerebrospinal fluid pathological markers in patients with Alzheimer's disease / 中华神经医学杂志

Objective:To explore the correlations of brain network functional connectivity (FC) alterations with cerebrospinal fluid (CSF) pathological biomarkers in patients with Alzheimer's disease (AD).Methods:A total of 39 patients with cognitive impairment, admitted to Department of Neurology, Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2020 to December 2022 were recruited; 23 patients were with AD and 16 with non-AD. Clinical data were compared between the 2 groups. Resting-state functional MRI (rs-fMRI) data were collected, and FC differences between brain networks and FC differences within brain networks were compared by independent component analysis. Correlations of FC differences between brain networks and FC differences within brain networks with concentrations of β-amyloid protein 1-42 (Aβ 1-42) and Tau protein in CSF were analyzed. Results:Compared with the non-AD group, AD group had significantly lower Aβ 1-42 in CSF ( P<0.05). Compared with those in the non-AD group, FC alterations between the left frontoparietal network (lFPN) and anterior default mode network (aDMN) and between the visual network (VN) and posterior cingulate cortex (PCC), as well as FC alterations in lFPN, were significantly increased in AD group ( P<0.05). Compared with those in the non-AD group, FC alterations between lFPN and cerebellar network (CEN), and FC alterations in aDMN, sensorimotor network (SMN) and VN were significantly decreased in AD group ( P<0.05). In AD group, FC in SMN was positively correlated with total Tau and phosphorylated-Tau181 in CSF ( P<0.05); FC between VN and PCC was positively correlated with total Tau in CSF ( P<0.05). CSF Aβ 1-42 was positively correlated with FC alterations in aDMN and VN, but negatively correlated with FC in FPN ( P<0.05). Conclusion:In AD patients, characteristic changes in FC within and between multiple brain networks are noted, which are related to changes of Tau protein and Aβ 1-42 in CSF.

Regulation effect of dopamine on sepsis-associated macrophage functions and the mechanisms involved / 中国小儿急救医学

Sepsis is a life-threatening organ dysfunction caused by the host disordered response to infections.As one of the most important innate immune cells in the body，macrophages can maintain the immune homeostasis by recruiting other immune cells，clearing pathogens，presenting antigens，and play important regulatory roles in infectious diseases such as sepsis by releasing inflammatory factors.As a critical neurotransmitter，dopamine not only participates in the neurological processes such as learning and cognition，but also regulates the immune processes，including regulating the activation，proliferation and functional changes of immune cells such as neutrophils，lymphocytes，monocytes and macrophages.Current studies demonstrate that during the infection and inflammation process of sepsis，the phagocytosis，polarization，and release of inflammatory factors of macrophages are regulated by dopamine.This review summarized the recent research progress on the regulatory functions and the underlying mechanisms of dopamine on macrophages in sepsis.

Correlations of hippocampal subfield volumes with cerebrospinal fluid biomarkers in patients with Alzheimer's disease / 中华神经医学杂志

Objective:To study the correlations of hippocampal subfield volumes with cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) patients.Methods:Forty-nine patients with cognitive impairment, including 30 AD patients and 19 non-AD patients, were recruited in Department of Neurology, Drum Tower Clinical College, Nanjing University of Chinese Medicine from May 2017 to December 2021. Concentrations of Aβ 1-42, total tau protein and phosphorylated tau protein in CSF were analyzed by enzyme-linked immunosorbent assay (ELISA). Volumes of 12 hippocampal subfields were calculated using FreeSurfer image analysis. Differences of clinical data, neuropsychological scores and CSF biomarker concentrations between the 2 groups were compared. Partial correlation was performed to analyze the correlations of volumes of hippocampal subfields with CSF biomarker concentrations. Results:AD patients had significantly lower Mini-mental State Examination (MMSE) scores and Aβ 1-42 concentration in CSF than non-AD patients ( P<0.05); AD patients had significantly lower volumes of the right hippocampal parasitulum, dentate gyrus and CA4 than non-AD group ( P<0.05); the right parasubiculum volume was negatively correlated with CSF Aβ 1-42 ( r=-0.445, P=0.023) and positively correlated with CSF P-tau ( r=0.393, P=0.047) in AD patients. Volumes of left hippocampus tail, parasubiculum, CA1, molecular layer, dentate gyrus, CA3 and CA4 were negatively correlated with CSF total tau ( P<0.05). No significant correlation was noted between hippocampal subfield volumes and CSF biomarker concentrations in non-AD patients. Conclusion:Some right hippocampal subfields in AD patients atrophy compared with those in non-AD patients with cognitive impairment; the right parasubiculum may play a compensatory role in disease process, while volumes of the left hippocampus decreased with increased CSF total tau.

Progress in role of intercellular mitochondrial transfer in diabetes and its complications / 中国病理生理杂志

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and has become a com-mon chronic disease worldwide.Mitochondria play key roles in energy production,signal transduction and apoptosis.Mi-tochondrial dysfunction is an important factor that promotes the development of diabetes and its complications.Maintaining mitochondrial function is expected to have a therapeutic effect on diabetes and its complications.Mitochondria can be transferred between cells,replacing dysfunctional mitochondria with exogenous healthy mitochondria and thereby reversing cell damage.Mitochondrial transfer through actin-based tunnel nanotubes,extracellular vesicles,connexins,cell fusion and extrusion has been shown to restore the bioenergetics of damaged mammalian cells.In addition,mitochondrial trans-plantation,which is an innovative strategy to treat mitochondrial diseases by increasing and replacing mitochondria,has at-tracted increasing attention.This article focuses on improving mitochondrial function in damaged cells as an entry point for the treatment of diabetes and its complications,focusing on the role of mitochondrial transfer among cells in diabetes and its complications.

Clinical efficacy of fractional CO 2 laser treatment for vaginal relaxation syndrome / 中华医学美学美容杂志

Objective:To evaluate the clinical efficacy and safety of fractional CO 2 laser for the treatment of vaginal relaxation syndrome. Methods:Twenty-one females with vaginal relaxation syndrome receiced between December 2016 and January 2017 in our department were treated for 3 times at 1 month interval with femilift fractional CO 2 laser. Vaginal palpation, vaginal squeeze pressure test, vaginal ultrasound, pelvic floor MRI, and Incontinence Questionnaire Short-Form (ICIQ-SF) assessments were performed at baseline and at post-treatment. Results:Significant improvement in female sexual dysfunction and stress urinary incontinence was especially seen based on patient＇s feelings after treatments. A noted progressive differences were observed in FSFI and vaginal pressure test, which were much higher after treatment than before treatment ( P<0.01). Moreover, in 13 cases suffering from mild to moderate stress urinary incontinence (SUI), fractional CO 2 laser treatment was associated with a significant improvement of ICIQ-SF scores ( P<0.01). All subjects successfully completed the study with no adverse events such as infections, bleeding and pain, etc. Conclusions:Fractional CO 2 laser treatment is an effective treatment for female sexual dysfunction and stress urinary incontinence caused by vaginal relaxation syndrome.

Effect ofRong-ShuanCapsule on Rodent Tolerance against Cerebral Ischemia, Hypoxia and Cerebral Reserve Capacity / 世界科学技术-中医药现代化

This study was aimed to observe the effect ofRong-Shuan (RS) capsule on rodent tolerance against cerebral ischemia, hypoxia and cerebral reserve capacity, which was related to promote blood circulation and remove blood stasis. Acute cerebral ischemia and anoxia models were established by permanent left carotid artery ligation on C57 BL/6 mice and hypoxia inhalation (O2?N2 = 8?92) for 15 min. Duodenal administration of RS capsule at different doses (100, 200 or 400 mg·kg-1) or saline were given 10 min after ischemia onset. The local brain blood circulation changes and neurobehavioral function were evaluated 24 h after ischemia onset. SD rats were given RS capsule at different doses (75, 150, 300 mg·kg-1) or saline. The effect of RS capsule on improvement of microcirculation disturbance induced by high molecular dextran was observed. The results showed that compared with the sham operation group, the brain blood circulation in the model group was significantly decreased; the cerebral infarction area increased; and the behavioral score after cerebral hypoxia was significantly increased (P < 0.05, orP < 0.01). Meanwhile, after the injection of high molecular dextran among rats in the model group, the cerebral leptomeninx microcirculation was obviously slowed down at 3 timepoints, which were 10, 20 and 30 min. Compared with the model group, RS capsule (400 mg·kg-1) can significantly increase the local blood circulation in the brain of mice, improve behavioral disturbance, reduce cerebral ischemia area (P< 0.05, orP < 0.01). RS capsule can also improve blood flow velocity and flow pattern in cerebral leptomeninx microcirculation disturbance induced by high molecular dextran at different timepoints (P < 0.05, orP < 0.01). It was concluded that RS capsule can increase the tolerance against cerebral ischemia, hypoxia and cerebral reserve capacity in order to protect the neural tissues to promote neuronal recovery.

Study on Effect ofQi-supplementing and Depression-relieving ofJie-Du Tong-LuoCapsule on Post-stroke Depression Rat Model / 世界科学技术-中医药现代化

This study was aimed to observe behavioral changes of post-stroke depression (PSD) rats, and to assess effect ofJie-Du Tong-Luo(JDTL) capsule onqi-supplementing and depression-relieving. Microspheres were injected from external carotid artery of rats under anesthesia to prepare the multiple cerebral infarction. Aftermid long term feeding, PSD rat model was established. Then, open-field test (OFT), tail suspension test (TST), forced swimming test (FST) and glucose preference test were employed to study behavioral changes of rats. The results showed that rats suffered multiple cerebral infarction after mid long term feeding formed PSD, which were indicated by reduced food consume, slow body weight increasing, reduction of spontaneous movement and inquiry activity, prolonged accumulative immobility time in TST, FST and lowered glucose preference, compared with rats in the normal group. Compared with the model group, rats in the JDTL capsule group andBu-Chang Xin-Nao-Tonggroup showed larger body weight increase, higher scores in OFT, reduced immobility time in TST, FST, and elevated glucose preference. It was concluded that JDTL capsule had significant efficacy on rats’ body weight, behavior and glucose preference, which might be its pharmacological basis onqi-supplementing and depression-relieving.

Study on Qi-supplementing and Mind-tranquilizing Efficacy ofLing-Qi-JiaOral Solution on Heart-spleen Deficiency Mouse / 世界科学技术-中医药现代化

This study was aimed to observe the body weight and behavioral changes of heart-spleen deficiency mouseandtoassesstheefficacyofLing-Qi-Jia (LQJ)oralsolutiononqi-supplementingandmind-tranquilizing. The heart-spleen deficiency syndrome mouse model was established by using loading swimming anddrugdaily.Thebodyweight,foodconsumption,intestinepropulsion,tailsuspensiontest (TST),forced swimmingtest (FST),sleepingtimeandtheamountofbrainneurotransmitterweredetected.Theresultsshowed that mouse suffered loading swimming and drug formed heart-spleen deficiency syndrome model, which were indicated by lowering body weight and food consumption, shortened time in FST, prolonged accumulative immobility time in TST, intestine propulsion hyperfunction, shortened sleeping time and lowering brain neurotransmitter amount. LQJ oral solution can obviously improve experiment indexes mentioned above. It was concluded that LQJ oral solution, which can improve insomnia due to heart-spleen deficiency, might had close relation to the efficacy of qi-supplementing and mind-tranquilizing. Meanwhile, changes of brain neurotransmitters might also be the material basis on its efficacy.

Effects of heat treatment and UVB radiation alone or in combination on the expression of heat shock protein 72 in human epidermal melanocytes / 中华皮肤科杂志

ObjectiveTo explore the effects of heat treatment and ultraviolet B (UVB) radiation alone or in combination on the expression of heat shock protein (HSP) 72 in human epidermal melanocytes.Methods Melanocytes were obtained from human foreskin,and subjected to primary culture.After 3 to 5 passages,the melanocytes were classified into 4 groups:control group (receiving no treatment),heat treatment group (treated with heat at 42 ℃ for 1 hour every day for 3 days),UVB group(irradiated with UVB at 50 mJ/cm2 daily for 3days),combination group(treated with heat at 42 ℃ for 1 hour followed by irradiation with UVB at 50 mJ/cm2daily for 3 days).After another 2- to 6-hour culture following the last treatment,melanocytes were collected and subjected to real time PCR and Western blot for the detection of HSP72 mRNA and protein expression,respectively.ResultsThe mRNA and protein expressions of HSP72 were significantly higher in the heat treatment group and combination group than in the control group (mRNA:6.584 ± 0.871 and 7.269 ± 0.454 vs.0.975 ± 0.089,both P ＜ 0.001; protein:2.022 ± 0.058 and 2.080 ± 0.045 vs.0.532 ± 0.033,both P ＜ 0.001 ),but was similar between the UVB group and control group (mRNA:0.832 ± 0.084 vs.0.975 ± 0.089,P ＞ 0.05;protein:0.546±0.021 vs.0.532 ± 0.033,P ＞ 0.05).The ANOVA of factorial design showed that neither heat treatment nor UVB irradiation had interaction effect on the mRNA or protein expression of HSP72 (F =2.106,1.399 respectively,both P ＜ 0.05).ConclusionsHeat treatment can cause an increase in the expression of HSP72,which may enhance the function of melanocytes and protect melanocytes from UVB induced damage.

Effects of heat treatment on the activity of cultured human melanocytes irradiated by ultraviolet B in vitro / 中华皮肤科杂志

ObjectiveTo investigate the effect of heat treatment combined with narrow band ultraviolet B(NB-UVB) on cultured normal human melanocytes in vitro.MethodsMelanocytes were isolated from the foreskin of normal human,cullured in vitro,and irradiated with NB-UVB of different doses(20,30,50,70,90,120 and 180 mJ/cm2).Then,MTT assay was performed to evaluate the proliferation and activity of melanocytes to determine the optimal dose of UVB for the next experiment.Melanocytes were classified into 3 groups to be treated with heat at 42 ℃ for 1 hour (heat group),irradiated with UVB at 50 mJ/cm2 (UVB group),or irradiated with UVB at 50 mJ/cm2 followed by heat treatment at 42 ℃ for 1 hour (combination group),daily for 3 successive days; those receiving no treatment served as the control.After 24-hour culture following the last treatment,tyrosinase activity was evaluated with L-dopa as the substrate,melanin content was detected by NaOH assay,and cell cycle stages were determined by flow cytometry.ResultsNB-UVB irradiation decreased the viability of melanocytes in a dose-dependent manner,and the optimum dose of UVB was 50 mJ/cm2.The tyrosinase activity of melanocytes was 0.244 ± 0.018 and 0.310 ± 0.015 respectively in the UVB group and combination group,and increased by 3.8％ (P ＜ 0.05) and 31.9％ (P ＜ 0.05) respectively compared with the control group (0.235 ± 0.018); the melanin content was 0.201 ± 0.016 and 0.286 ± 0.019,respectively in the UVB group and combination group,and increased by 17.5％ (P ＜ 0.05 ) and 67.3％ (P ＜ 0.05) compared with the control group (0.171 ± 0.016).In comparison with the control group,the percentage of melanocytes in G1 phase was decreased by 23.94％ in the UVB group(P＜ 0.05) and 33.51％ in the combination group(P ＜ 0.05),while that in S phase and G2 phase increased by 15.35％ (P ＜ 0.05 ) and 11.93％ (P ＜ 0.05),respectively in the UVB group,and 17.76％ (P ＞ 0.05) and 16.08％ (P ＞ 0.05),respectively in the heat group.ConclusionHeat treatment and NB-UVB can synergistically enhance the tyrosinase activity and accelerate melanogenesis,proliferation and differentiation,of melanocytes.

Influences of infrared irradiation on human epidermal melanocytes / 中华皮肤科杂志

ObjectiveTo observe the increasing effect of infrared irradiation on tyrosinase activity and melanin content in cultured normal human epidermal melanocytes in vitro and to explore the optimal dose of infrared irradiation.MethodsEpidermal melanocytes were isolated from normal human foreskin tissue,and subjected to primary culture.Methyl thiazolyl tetrazolium(MTT) assay was performed to evaluate the effect of different doses(0,20,60,80,100,140,240,320 J/cm2)of infrared light on the proliferation of melanocytes and to select the optimal irradiation dose.Then,melanocytes were irradiated with infrared light at the optimal dose for 3 consecutive days followed by the determination of tyrosinase activity,melanin content,and cell cycle via dopa oxidation assay,NaOH solubilization method and flow cytometry,respectively.ResultsThe best intervention dose of infrared light was 80 J/cm2.The tyrosinase activity(A492 nm) and melanin content(A492 nm)were 0.3601 ± 0.0301 and 0.2748 ± 0.0243 respectively in melanocytes after irradiation with infrared light of 80 J/cm2 for 3 days,significantly higher than those in unirradiated melanocytes(0.3114 ± 0.0341,0.2325 ±0.0254,respectively,both P ＜ 0.05),with an increase rate of 15.64％ and 18.19％ respectively.Cell cycle analysis revealed a decline in cell percentage in G1 phase(P ＜ 0.01 ) but a concomitant increase in cell percentage in G2 and S phase (both P ＜ 0.05) in irradiated melanocytes compared with unirradiated melanocytes.ConclusionsThe optimal dose of infrared light is 80 J/cm2 for the irradiation of melanocytes,and this dose of infrared light can increase melanin content,tyrosinase activity,differentiation and proliferation of melanocytes.

Effect of sailuotong capsule on Glu and GABA levels as well as NMDA receptor subtypes expression in recovery period of rat multiple cerebral infarction / 药学学报

The rat model of multi-infarct was adopted in this study to elucidate the protective mechanism of Sailuotong capsule (Sailuotong) in recovery period of multiple cerebral infarction. The effects of Sailuotong on levels of Glu, GABA and the expression of NMDA receptor subtypes including NR1, NR2A and NR2B, were detected. The multi-infarct model rats were established by injecting embolizing microsphere via internal carotid artery, and were given Sailuotong treatment (16.5 and 33.0 mg x kg(-1)) for 60 days. The pathological changes in brain ultrastructure were observed by transmission electron microscope. The levels of Glu and GABA in brain tissue were measured with high performance liquid chromatography. The expression of NMDA receptors including NR1, NR2A and NR2B in neurons was evaluated by immunohistochemical staining. Compared with the sham rats, abnormal changes were observed in ultrastructures of neurons, neuroglia cells and synapses of model rat brains. Moreover, significant decrease of Glu and GABA, as well as the elevated expression of NR1, NR2A and NR2B were detected in brain tissues. Sailuotong (16.5 and 33.0 mg x kg(-1)) could improve ultrastructure of cerebral tissue, facilitate synthesis of Glu and GABA, and down-regulate expression of NR1, NR2A and NR2B in neurons. The results demonstrated that Sailuotong could exert neuroprotective effects to some extent in the recovery phase of multiple cerebral infarction by promoting expression of NMDA receptors and synthesis of Glu and GABA.

Review on application of microdialysis in medicine study / 中国中药杂志

Recent publications are quoted to summarize multiple use of microdialysis in medical fields, especially in pharmacology and pharmacokinetics. Microdialysis was coupled with HPLC-ECD, HPLC-MS and other detectors to study endogenous substances and medicines, including neurotransmitters, amino acid, other endogenous metabolites and drugs as well as Chinese medicines. Microdialysis is a relatively new sampling technique and its advantages as well as disadvantages are briefly assessed. At the end of this review, an outlook to apply this technique in traditional Chinese medicine study is given forward.