Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective To investigate the effect of Ophiopogonin D on lipopolysaccharide(LPS)-induced apoptosis of alveolar epithelial cells by regulating the interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A549 AT Ⅱ cells cultured in vitro were randomly divided into four groups:control group,LPS group,LPS+Ophiopogonin D group,LPS+Ophiopogonin D+colivelin(JAK2/STAT3 signal activator)group,except for the control group,and cells in all other groups were established injury models while being grouped with Ophiopogonin D and colivelin for treatment.Cell counting kit-8(CCK-8)experiment and flow cytometry were applied to detect cell proliferation and apoptosis in each group;Western blotting was applied to detect the expression of IL-6/JAK2/STAT3 signaling pathway proteins of cells in each group.Results The apoptosis rates of A549 cells in control group,LPS group,LPS+Ophiopogonin D group and LPS+Ophiopogonin D+colivelin group were(2.52±0.73)％,(52.43±4.14)％,(1.67±0.52)％and(47.94±3.43)％;IL-6 protein levels were 0.14±0.03,0.49±0.05,0.17±0.04 and 0.45±0.06,and p-JAK2/JAK2 protein levels were 0.17±0.04,0.64±0.08,0.19±0.06 and 0.61±0.07;p-STAT3/STAT3 protein levels were 0.20±0.06,0.69±0.10,0.22±0.07 and 0.65±0.09;the apoptosis rates of AT Ⅱ cells were(3.01±0.69)％,(55.16±3.94)％,(2.35±0.71)％and(50.28±3.78)％;the levels of IL-6 protein were 0.11±0.03,0.87±0.13,0.19±0.04 and 0.84±0.12;the p-JAK2/JAK2 protein levels were 0.13±0.04,0.56±0.08,0.15±0.03 and 0.53±0.07;p-STAT3/STAT3 protein levels were 0.30±0.08,0.79±0.14,0.33±0.09 and 0.75±0.13.The above indexes:control group,LPS+Ophiopogonin D group compared with LPS group,LPS+Ophiopogonin D+colivelin group compared with LPS+Ophiopogonin D group,the differences were statistically significant(all P＜0.05).Conclusion Ophiopogonin D can reduce LPS induced inflammation and oxidative stress levels by inhibiting the activation of IL-6/JAK2/STAT3 signaling pathway,ultimately reducing LPS-induced apoptosis of alveolar epithelial cells.

OBJECTIVES: To observe the effects of zhongfeng cutong moxibustion (moxibustion therapy for unblocking and treating stroke) on the motor function and the structure of corticospinal tract (CST) in the patients with motor dysfunction during the recovery period of cerebral infarction, and to explore the central mechanism of this moxibustion therapy for improving the motor function. METHODS: Fifty patients with motor dysfunction during the recovery period of cerebral infarction were randomly divided into an observation group (25 cases, 1 case dropped out) and a control group (25 cases, 1 case dropped out). The patients in both groups underwent the conventional basic treatment. In the control group, acupuncture was applied to Baihui (GV 20) and Shuigou (GV 26), as well as Chize (LU 5), Neiguan (PC 6), Weizhong (BL 40) and Sanyinjiao (SP 6) etc. on the affected side. Besides the intervention of the control group, in the observation group, zhongfeng cutong moxibustion therapy was combined at Baihui (GV 20), Shenque (CV 8) and bilateral Zusanli (ST 36). Both acupuncture and moxibustion therapies were delivered once daily, 5 times a week, for 2 weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were compared between the two groups before and after treatment. The diffusion tensor imaging technique was used to observe the fractional anisotropy (FA) of CST at the bilateral whole segment, the cerebral cortex, the posterior limb of the internal capsule and the cerebral peduncle before and after treatment in the two groups. RESULTS: The scores of the upper and the lower limbs of FMA, as well as the total FMA score swere increased after treatment when compared with those before treatment in the two groups (P<0.05), the upper limb FMA score and the total FMA score in the observation group were higher than those in the control group (P<0.05), and NIHSS scores of the two groups were dropped compared with those before treatment (P<0.01). FA of CST at the bilateral sides of the posterior limb of the internal capsule and the whole segment on the focal side was improved in comparison with that before treatment in the observation group (P<0.05), and FA of CST at the healthy side of the whole segment was higher than that before treatment in the control group (P<0.05). CONCLUSIONS Zhongfeng cutong moxibustion improves motor function and reduces neurological deficits in the patients with motor dysfunction during the recovery period of cerebral infarction, which may be related to enhancing the remodeling of white matter fiber bundles in the corticospinal tract on the focal side of the whole segment and the bilateral posterior limb of the internal capsule.
Humans ; Moxibustion ; Pyramidal Tracts ; Diffusion Tensor Imaging ; Acupuncture Therapy ; Cerebral Infarction/therapy* ; Stroke/therapy* ; Acupuncture Points ; Treatment Outcome

ObjectiveTo investigate the effect of quantitative pulmonary administration of the essential oil from Alpiniae Zerumbet Fructus （EOAZF） on porcine pancreatic elastase （PPE）-induced emphysema in mice and explore its action mechanism. MethodC57BL/6J mice were randomly divided into five group， namely the control group， model group， low- （2 mg·kg^-1） and high-dose （20 mg·kg^-1） EOFAZ groups， and positive control dexamethasone （DEX，1 mg·kg^-1） group. The mice were treated with pulmonary administration of PPE using a microsprayer aerosolizer， once every seven days， for four times in total， for inducing emphysema. During this period， EOFAZ were administered with a quantitative microsprayer aerosolizer once every other day， for 14 times. The lung tissues were then sampled and stained with hematoxylin-eosin （HE） for observing the morphological changes and calculating the pulmonary mean linear intercept （MLI）. The concentrations of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the plasma were determined by enzyme-linked immunosorbent assay （ELISA）. The activities of superoxide dismutase （SOD） and catalase （CAT） and the content of malondialdehyde （MDA） in the lung tissues were measured using the biochemical assay kits. The protein expression levels of nuclear factor E₂-related factor 2 （Nrf2）， quinone oxidoreductase1 （NQO1）， B cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， and Bcl-2 in lung tissues were detected by Western blot. ResultThe results of lung morphological observation and MLI detection showed that compared with the control group， the model group showed obvious inflammatory infiltration， alveolar enlargement and fusion， and increased MLI （P<0.05）. Compared with the model group， EOFAZ effectively alleviated the pathological changes such as alveolar dilatation， pulmonary inflammatory cell infiltration， and lung cell apoptosis caused by PPE， and decreased the MLI （P<0.05）. As revealed by ELISA， the inflammatory level of mice in the model group increased significantly （P<0.01）， while the TNF-α， IL-1β， and IL-6 levels in the plasma were decreased after quantitative administration of EOFAZ （P<0.01）. Compared with the control group， the model group exhibited significantly enhanced oxidative stress （P<0.01）. After treatment with EOFAZ by quantitative administration， the activities of SOD and CAT in the lung tissue were increased （P<0.01） and the content of MDA was decreased （P<0.01）. Western blot results demonstrated that the apoptosis-related protein expression in the model group was increased significantly as compared with that in the control group （P<0.01）， whereas the expression levels of antioxidant stress proteins Nrf2 and NQO1 declined （P<0.05）. The relative protein expression of apoptosis-related proteins Bax/Bcl-2 in the EOFAZ groups was lower than that in the model group （P<0.01）， while the expression of antioxidant stress proteins Nrf2 and NQO1 was higher （P<0.05）. ConclusionQuantitative pulmonary administration of EOFAZ effectively alleviates the inflammation and oxidative stress， reduces lung cell apoptosis， and hinders the occurrence and development of emphysema. Its antioxidant mechanism is closely related to the up-regulation of Nrf2 and its downstream NQO1.

This paper summarizes Professor ZHANG Jian-bin's experience in "moving cupping therapy on the back" in clinical practice. Professor ZHANG Jian-bin is good at applying the theory of governor vessel to the clinical diagnosis and treatment. He believes that the moving cupping therapy is the supplementation of "spinal therapy" in clinical diagnosis and treatment. He emphasizes that during the moving cupping therapy exerted, the physicians should observe carefully to in-time obtain the perceived feedback of treatment in patients. Afterward, the cupping marks left should be inspected to discover the location of disorder in the body, thus, a targeted treatment can be provided. Besides, the prognosis of the disease can be judged by the feedback after many treatments with the moving cupping therapy. The moving cupping therapy displays its important value in the diagnosis and treatment of disease, as well as the evaluation of the prognosis.
Male ; Humans ; Cupping Therapy ; Meridians ; Acupuncture Points ; Acupuncture Therapy ; Medicine, Chinese Traditional

A series of novel xanthones with terminal amine substituents at xanthone's C3 and C6 positions were designed and synthesized as potential ligands for telomeric G-quadruplex DNA. All the compounds in this series were bound to telomeric G-quadruplex in a "thread intercalation" manner that illustrated both in molecular docking and spectrometric studies. Among them, 10c and 10d showed better binding abilities and specific affinity toward G-quadruplex DNA HTG21 over ctDNA in the fluorescence assay. The antiproliferative activities of four screened compounds were examined in three cancer cells by MTT in vitro, and their inhibitory effects were observed at low micromolar ranges. In addition, the PCR stop assay demonstrated that 10c and 10d effectively inhibited the amplification ability of telomerase.

OBJECTIVETo investigate the relationship of the common Traditional Chinese Medicine (TCM) syndrome pattern of chronic pelvic pain syndrome (CPPS) with the contents of substance p and beta endorphin in the plasma, and provide reference data for the clinical diagnosis, differentiation and treatment of CPPS by TCM.

METHODSWe observed 98 cases of CPPS, which were classified into a lower-part damp-heat invasion group (group A, n = 32), a blood stasis-induced collateral obstruction group (group B, n = 34), and a damp-heat stagnation group (group C, n = 32) according to the TCM syndrome differentiation. Another 35 normal healthy young men were enrolled as controls. We measured the contents of substance p and beta endorphin in the plasma by immunoradiometry and ELISA, and analyzed their relationship with the TCM syndrome pattern.

RESULTSThe contents of plasma substance p were significantly higher in groups A ([1135.76 +/- 166.45] pg/ml), B ([1 337.84 +/- 170.81] pg/ml), and C ([1 210.01 +/- 162.27] pg/ml) than in the control ([574.99 +/- 113.09] pg/ml) (all P < 0.01), while the contents of plasma beta endorphin in groups A ([212.70 +/- 29.49] pg/ml), B ([157.99 +/- 24.01] pg/ml), and C ([180.81 +/- 20.20] pg/ml) were remarkably lower than that in the control ([274.73 +/- 27.64] pg/ml) (all P < 0.01).

CONCLUSIONIn the plasma of CPPS patients, the content of substance p is significantly elevated and that of beta endorphin markedly reduced, which suggests that they may be involved in the inflammatory reaction of CPPS. The levels of plasma substance p and beta endorphin can be used as valuable reference for the TCM classification of chronic prostatitis.

Case-Control Studies ; Chronic Disease ; Humans ; Male ; Medicine, Chinese Traditional ; adverse effects ; Pelvic Pain ; blood ; classification ; Prostatitis ; blood ; classification ; Substance P ; blood ; Syndrome ; beta-Endorphin ; blood

OBJECTIVETo compare the efficacy difference in the treatment of chronic pelvic pain syndrome of Sev-damp-heat stagnation pattern between acupoint catgut embedding therapy and western medication.

METHODSenty cases were randomized into a catgut embedding group (40 cases) and a western medication group (30 cases) at the ratio of 4 : 3. In the catgut embedding group, the catgut embedding therapy was applied to Sanyinjiao (SP 6), Quchi (LI 11), Huiyin (CV 1), Zusanli (ST 36), Zhongji (CV 3), Shenshu (BL 23), etc. The treatment was given once every two weeks, the treatment for 4 weeks was as one session and totally 2 sessions were required. In the western medication group, tamsulosin hydrochloride capsules 0. 2 mg, oral administration, once a day, and Indometacin sustained release tablets, 75 mg, once a day, 3 tablets each time were prescribed. The symptom score of TCM, score of NIH Chronic Prostatitis Symptom Index (NIH-CPSI), lecithin body number in prostatic fluid, (SAS) score of Self-Rating Anxiety Scale and score of Self-Rating Depression Scale (SDS) were compared before and after treatment in the patients of the two groups. The efficacy was evaluated in the two groups.

RESULTS(1)The total effective rate was 91. 9% (34/37) in the catgutembedding group and was 86. 2% (25/29) in the western medication group. The efficacy in the catgutembedding group was better than that in the western medication group (P<0. 05). (2) The symptom score of TCM was all reduced significantly after treatment in the two groups (both P<0.01), and the result in the catgut embedding group was superior to the western medication group (6.42 +/-2. 81 vs 10. 99+/-3. 11 ,P<0. 01). (3) Lecithin body number was increased apparently in the two groups after treatment (both P<0.01), and the result in the catgut-embedding group was superior to the western medicine group (33.56+/-5.88 vs 29. 78+/-7. 06,P<0. 05). (4) Total score of NIH-CPSI, score of pain, score of SAS and score of SDS were all improved apparently after treatment in the two groups (all P<0. 01), and the results in the catgut embedding group were superior to the western medication group (P<0. 01, P<0. 05).

CONCLUSIONThe acupoint catgut embedding therapy achieves the superior efficacy on chronic pelvic pain syndrome of damp-heat stagnation pattern as compared with conventional western medicine. This therapy relieves clinical symptoms, improves the states of anxiety and depression and increases lecithin body number obviously.

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Catgut ; utilization ; Chronic Disease ; therapy ; Humans ; Male ; Middle Aged ; Pelvic Pain ; therapy ; Prostatitis ; therapy ; Treatment Outcome ; Young Adult

OBJECTIVE: To explore the relationship between the expression of EIIIA+ fibronectin in incised wound of rat's skin and injury time. METHODS: The wounding model was established by cutting the dorsal skin of 48 adult SD rats. The rats were sacrificed at the pre-set injury time as immediately, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, and 8 h. The skin samples were taken at the margin of wound. The expression of the EIIIA? fibronectin was detected by immunohistochemistry and Western blotting and the relationship be- tween its expression and injury time was observed. Results The expression of EIIIA+ fibronectin was not observed immediately. The basal cell of skin began to show positive expression 0.5 h after injury. With the extension of injury time, positive staining became stronger. The value of relative optical density was gradually increased with prolonged injury time by the Western blotting analysis. CONCLUSION The expression of EIIIA+ fibronectin could be used for estimation of injury time in the early stage of skin injury.
Animals ; Fibronectins/metabolism* ; Immunohistochemistry ; Proteins/metabolism* ; Rats ; Rats, Sprague-Dawley ; Skin/metabolism* ; Staining and Labeling ; Time Factors