Considerations for the Use of Photobiomodulation in the Treatment of Retinal Diseases.

Photobiomodulation (PBM) refers to the beneficial effect produced from low-energy light irradiation on target cells or tissues. Increasing evidence in the literature suggests that PBM plays a positive role in the treatment of retinal diseases. However, there is great variation in the light sources and illumination parameters used in different studies, resulting in significantly different conclusions regarding PBM's therapeutic effects. In addition, the mechanism by which PBM improves retinal function has not been fully elucidated. In this study, we conducted a narrative review of the published literature on PBM for treating retinal diseases and summarized the key illumination parameters used in PBM. Furthermore, we explored the potential molecular mechanisms of PBM at the retinal cellular level with the goal of providing evidence for the improved utilization of PBM in the treatment of retinal diseases.

Short-term efficacy of music therapy combined with α binaural beat therapy in disorders of consciousness.

Objective: To investigate the short-term effect of music therapy combined with binaural frequency difference therapy on patients with consciousness disorder. Materials and methods: Ninety patients with definite diagnosis of disorders of consciousness (DOC) were selected. These patients were randomly divided into control group, experiment 1 group and experiment 2 group, with 30 patients in each group. The control group was treated with routine clinical treatment and rehabilitation. In experiment 1 group, music therapy was added to the control group. In experimental group 2, music therapy combined with binaural α frequency difference therapy was added to the control group. All patients were assessed before and after 30 treatments. The assessment items included Glasgow Coma Scale (GCS), Coma Recovery Scale revised (CRS-R), electroencephalogram (EEG), upper somatosensory evoked potential (USEP), and brainstem auditory evoked potential (BAEP). Results: Before treatment, there were no significant differences in GCS score, CRS-R score, USEP, BAEP, and EEG scores among the three groups (P > 0.05). After 30 times of treatment, GCS score, CRS-R score, USEP, BAEP, and EEG scores in 3 groups were significantly higher than those before treatment (P < 0.05), and experimental group 2 >experimental group 1 >control group (P < 0.05). And the consciousness rate of experimental group 2 was better than experimental group 1, experimental group 1 was better than the control group and the difference was statistically significant (P < 0.05). Conclusion: Music therapy combined with binaural α frequency difference therapy is more effective in stimulating DOC patients.

Effects of Interactive Dynamic Scalp Acupuncture on Motor Function and Gait of Lower Limbs after Stroke: A Multicenter, Randomized, Controlled Clinical Trial.

OBJECTIVE: To evaluate the effects of interactive dynamic scalp acupuncture (IDSA), simple combination therapy (SCT), and traditional scalp acupuncture (TSA) on motor function and gait of the lower limbs in post-stroke hemiplegia patients. METHODS: A total of 231 patients with post-stroke hemiplegia was randomly divided into IDSA (78 cases), SCT (78 cases), and TSA (75 cases) groups by a random number table. Scalp acupuncture (SA) and lower-limb robot training (LLRT) were both performed in the IDSA and SCT groups. The patients in the TSA group underwent SA and did not receive LLRT. The treatment was administered once daily and 6 times weekly for 8 continuous weeks, each session lasted for 30 min. The primary outcome measures included Fugl-Meyer assessment of the lower extremity (FMA-LE), berg balance scale (BBS), modified barthel index (MBI), and 6-min walking test (6MWT). The secondary outcome measures included stride frequency (SF), stride length (SL), stride width (SW), affected side foot angle (ASFA), passive range of motion (PROM) of the affected hip (PROM-H), knee (PROM-K) and ankle (PROM-A) joints. The patients were evaluated before treatment, at 1- and 2-month treatment, and 1-, and 2-month follow-up visits, respectively. Adverse events during 2-month treatment were observed. RESULTS: Nineteen patients withdrew from the trial, with 8 in the IDSA and 5 in the SCT groups, 6 in the TSA group. The FMA-LE, BBS, 6MWT and MBI scores in the IDSA group were significantly increased after 8-week treatment and 2 follow-up visits compared with the SCT and TSA groups (P<0.05 or P<0.01). Compared with pre-treatment, the grade distribution of BBS and MBI scores in the 3 groups were significantly improved at 1, 2-month treatment and 2 follow-up visits (P<0.05 or P<0.01). The SF, PROM-H, PROM-K and PROM-A in the IDSA group was significantly increased compared with the SCT and TSA groups after 8-week of treatment (P<0.05 or P<0.01). Compared with the SCT group, ASFA of the IDSA group was significantly reduced after 8-week of treatment (P<0.05). SF, SL, PROM-K and PROM-A were significantly increased at the 2nd follow-up visit whereas the ASFA was significantly reduced in the IDSA group compared with the SCT groups at 1st follow-up visit (P<0.05 or P<0.01). The SF was significantly increased in the SCT group compared with the TSA group after 8-week treatment (P<0.05). Compared with the TSA group, PROM-K, PROM-A were significantly increased at the 2nd follow-up visit (P<0.05). CONCLUSIONS: The effects of IDSA on lower-limb motor function and walking ability of post-stroke patients were superior to SCT and TSA. The SCT was comparable to TSA treatment, and appeared to be superior in improving the motion range of the lower extremities. (Registration No. ChiCTR1900027206).

Effect of Interactive Dynamic Scalp Acupuncture on Post-Stroke Cognitive Function, Depression, and Anxiety: A Multicenter, Randomized, Controlled Trial.

OBJECTIVE: To compare the clinical effects of interactive dynamic scalp acupuncture (IDSA), simple combination therapy (SCT), and traditional scalp acupuncture (TSA) on cognitive function, depression and anxiety in patients with post-stroke cognitive impairment. METHODS: A total of 660 patients with post-stroke cognitive impairment who were admitted to 3 hospitals in Shenzhen City between May 2017 and May 2020 were recruited and randomly assigned to the IDSA (218 cases), SCT (222 cases) and TSA groups (220 cases) according to a random number table. All the patients received conventional drug therapy for cerebral stroke and exercise rehabilitation training. Scalp acupuncture and computer-based cognitive training (CBCT) were performed simultaneously in the IDSA group, but separately in the morning and in the afternoon in the SCT group. The patients in the TSA group underwent scalp acupuncture only. The course of treatment was 8 weeks. Before treatment (M0), 1 (M1) and 2 months (M2) after treatment, as well as follow-up at 1 (M3) and 2 months (M4), the cognitive function of patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) Scales; depression, anxiety, sleep quality, and self-care ability of patients were assessed using Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), and Modified Barthel Index (MBI), respectively. During this trial, all adverse events (AEs) were accurately recorded. RESULTS: There were no significant differences in the MMSE, MoCA, HAMD, HAMA, PSQI, and MBI scores among the 3 groups at M0 (all P>0.05). In the IDSA group, the MMSE, MoCA and MBI scores from M2 to M4 were significantly higher than those in the SCT and TSA groups, while the HAMD, HAMA and PSQI scores were significantly reduced (all P<0.01). The changes of all above scores (M2-M0, M4-M0) were significantly superior to those in the SCT and TSA groups (all P<0.01, except M4-M0 of HAMD). At M2, the severity of MMSE, HAMD, HAMA, PSQI and MBI in the IDSA group was significantly lower than that in the SCT and TSA groups (all P<0.01). There was no serious AE during this trial. CONCLUSIONS: IDSA can not only significantly improve cognitive function, but also reduce depression, anxiety, which finally improves the patient's self-care ability. The effect of IDSA was significantly better than SCT and TSA. (Trial registration No. ChiCTR1900027206).

[Scalp acupuncture combined with lower-limb intelligent feedback training for lower-limb motor dysfunction after stroke: a randomized controlled trial].

OBJECTIVE: To compare the efficacy of scalp acupuncture combined with lower-limb intelligent feedback training and lower-limb intelligent feedback training alone for lower-limb motor dysfunction after stroke. METHODS: A total of 154 patients with lower-limb motor dysfunction after stroke were randomly divided into an observation group (76 cases, 6 cases dropped off) and a control group (78 cases, 8 cases dropped off). The patients in both groups were treated with conventional medication and exercise rehabilitation training. In addition, the patients in the observation group were treated with scalp acupuncture combined with lower-limb intelligent feedback training. The scalp acupuncture was given at upper 1/5 of the anterior oblique line of parietal temporal area and upper 1/5 of the posterior oblique line of parietal temporal area. The patients in the control group were treated with lower-limb intelligent feedback training alone. All the treatment was given once a day, 6 days a week, totaling for 8 weeks. The affected-side lower-limb Brunnstrom stage and modified Ashworth scale (MAS) grade, 6-minute walk test (6MWT), Berg balance scale (BBS) score and modified Barthel index (MBI) score were evaluated before and after treatment in the two groups. The plantar pressure was measured by gait function evaluation system. RESULTS: Compared before treatment, the Brunnstrom stage in the two groups was improved after treatment (P<0.01); the MAS grade in the observation group was improved after treatment (P<0.01); the Brunnstrom stage and MAS grade in the observation group were superior to those in the control group (P<0.01, P<0.05). After treatment, the 6MWT, BBS and MBI scores in the two groups were increased (P<0.05), and those in the observation group were higher than those in the control group (P<0.05). After treatment, the touchdown area of health-side hind foot, affected-side front-hind foot and bilateral full foot in the observation group was increased (P<0.05), and the touchdown area of affected-side front-hind foot and full foot in the observation group was larger than that in the control group (P<0.05). The weight-bearing ratio of health-side forefoot and full foot in the observation group was decreased after treatment (P<0.05), and the weight-bearing ratio of affected-side forefoot, hind foot and full foot was increased after treatment (P<0.05). The weight-bearing ratio of health-side forefoot and full foot in the observation group was lower than that in the control group (P<0.05), and the weight-bearing ratio of health-side hind foot, affected-side forefoot and affected-side full foot in the observation group was higher than that in the control group (P<0.05). CONCLUSION: The scalp acupuncture combined with lower-limb intelligent feedback training could reduce the muscle tension of lower limbs, promote the separation movement mode of lower limbs, improve the plantar pressure distribution, and improve the balance ability and walking ability in stroke patients, and the curative effect is better than lower-limb intelligent feedback training alone.

[Interactive scalp acupuncture for cognitive dysfunction after stroke: a randomized controlled trial].

OBJECTIVE: To compare the efficacy of interactive scalp acupuncture, scalp acupuncture alone and scalp acupuncture plus cognitive training for cognitive dysfunction after stroke. METHODS: A total of 660 patients with cognitive dysfunction after stroke were randomly divided into an interactive scalp acupuncture group (218 cases, 18 cases dropped off), a scalp acupuncture group (220 cases, 20 cases dropped off) and a scalp acupuncture plus cognitive training group (222 cases, 22 cases dropped off). All the patients were treated with routine medication and exercise rehabilitation training. The interactive scalp acupuncture group was treated with scalp acupuncture on the parietal midline, and contralateral anterior parietal temporal oblique line and posterior parietal temporal oblique line at the same time of cognitive training; the scalp acupuncture group was treated with scalp acupuncture alone, and the scalp acupuncture plus cognitive training group was treated with scalp acupuncture and cognitive training in the morning and afternoon respectively. All the treatments were given once a day, 6 times a week for 8 weeks. Montreal cognitive assessment (MoCA) scale score was used to evaluate the cognitive function before treatment, 4 weeks and 8 weeks into treatment. RESULTS: Compared before treatment, the total score of MoCA was increased after 4-week treatment and 8-week treatment in the three groups (P<0.01), and the score in the interactive scalp acupuncture group was higher than that in the scalp acupuncture group and the scalp acupuncture plus cognitive training group (P<0.05, P<0.01). Compared before treatment, each item score of MoCA was increased after 8-week treatment in the three groups (P<0.01), and the score in the interactive scalp acupuncture group was higher than that in the scalp acupuncture group and the scalp acupuncture plus cognitive training group (P<0.01). Except for the attention, the remaining items scores of MoCA in the scalp acupuncture plus cognitive training group were higher than those in the scalp acupuncture group (P<0.01). CONCLUSION: The interactive scalp acupuncture could significantly improve the cognitive function in patients with cognitive dysfunction after stroke, and the efficacy is superior to scalp acupuncture alone and scalp acupuncture plus cognitive training.

Highly selective monitoring of in-source fragmentation sapogenin product ions in positive mode enabling group-target ginsenosides profiling and simultaneous identification of seven Panax herbal medicines.

In-source fragmentation of ginsenosides in the positive ESI mode (pISF-G) frequently occurs, which results in little fragment information useful for the structural elucidation. We are aimed to unveil the genesic mechanism and explore its potential significance in quality control of Ginseng and the related compound formulae. By applying six high-resolution mass spectrometers from Agilent, Waters, and Thermo Fisher, we could primarily demonstrate the susceptibility of pISF-G. The ion clusters in the positive full-scan MS1 spectra were generated from the protonated sapogenins by successive elimination of H2O, and showed specificity for ginsenoside classification. Selective ion monitoring (SIM) of the sapogenin product ions could delineate group-target ginsenoside profiles from Ginseng. A high-selectivity characteristic chromatogram (CC) was elaborated for Ginseng, on the Vion™ IMS-QTOF mass spectrometer by IM (ion mobility) separation and quadrupole filtering of four sapogenin fragments (m/z 407.37/CCS 206.24 Å2; m/z 423.36/CCS 211.26 Å2; m/z 439.36/CCS 209.60 Å2; m/z 457.37/CCS 217.81 Å2). Chemometric analysis, based on the CC data of seven Ginseng drugs (P. ginseng, P. quinquefolius, P. notoginseng, Red ginseng, leaf of P. ginseng, P. japonicus, and P. japonicus var. major), disclosed 35 marker compounds. We could readily discriminate among P. ginseng, P. quinquefolius, and P. notoginseng, in 15 different compound formulae by identifying these marker compounds on both the Vion IMS-QTOF and QTrap 4500 mass spectrometers. Conclusively, SIM of the pISF-G sapogenin product ions renders a new concept of CC enabling the group-target profiling of ginsenosides and authentication of Ginseng and the related compound formulae.

Simultaneously targeted and untargeted multicomponent characterization of Erzhi Pill by offline two-dimensional liquid chromatography/quadrupole-Orbitrap mass spectrometry.

Large-scale targeted and untargeted metabolites characterization can be achieved by feat of different liquid chromatography/mass spectrometry (LC-MS) platforms by multiple MS experiments or using data-independent acquisition followed by precursor-product ions matching based on certain algorithms. The resulting insufficiency in efficiency and availability greatly restricts the applicability of these strategies in large-scale profiling and identification of various metabolites. A strategy simultaneously enabling both the targeted and untargeted metabolites characterization is established on a Q Exactive hybrid quadrupole-Orbitrap mass spectrometer, by integrating precursor ions list-triggered data-dependent MS2 acquisition (PIL/dd-MS2) of the targeted components and using the "If idle-pick others" (IIPO) function to induce untargeted metabolites fragmentation. A compounds-specific mass defect filter (MDF) algorithm is proposed as a method to generate the PIL. As a proof of concept, this strategy coupled with offline two-dimensional liquid chromatography (2D-LC) was applied to identify the multicomponents of a traditional Chinese medicine formula Erzhi Pill (EZP). A rigid MDF vehicle was elaborated by orthogonal screening of the integer mass and integer mass-dependent dynamic mass defects considering a variation of 20 ppm. The Full MS/dd-MS2 method enabling PIL and IIPO exhibited better performance than Full MS/dd-MS2 and Targeted SIM/dd-MS2 (selected ion monitoring) in respect of the sensitivity in identifying the targeted components and the ability to characterize more untargeted ones. As a consequence, 270 components were separated from EZP, and 146 thereof were selectively characterized. In conclusion, it is a practical, multifaced strategy facilitating the in-depth metabolites profiling and characterization of complex herbal and biological samples.

Profiling and identification of chemical components of Shenshao Tablet and its absorbed components in rats by comprehensive HPLC/DAD/ESI-MSn analysis.

Shenshao Tablet (SST), prepared from Paeoniae Radix Alba (PRA) and total ginsenoside of Ginseng Stems and Leaves (GSL), is a traditional Chinese medicine (TCM) preparation prescribed to treat coronary heart disease. However, its chemical composition and the components that can migrate into blood potentially exerting the therapeutic effects have rarely been elucidated. We developed an HPLC/DAD/ESI-MSn approach aiming to comprehensively profile and identify both the chemical components of SST and its absorbed ingredients (and metabolites) in rat plasma and urine. Chromatographic separation was performed on an Agilent Eclipse XDB C18 column using acetonitrile/0.1% formic acid as the mobile phase. MS detection was conducted in both negative and positive ESI modes to yield more structure information. Comparison with reference compounds (tR, MSn), interpretation of the fragmentation pathways, and searching of in-house database, were utilized for more reliable structure elucidation. A total of 82 components, including 21 monoterpene glycosides, four galloyl glucoses, two phenols from PRA, and 55 ginsenosides from GSL, were identified or tentatively characterized from the 70% ethanolic extract of SST. Amongst them, seven and 24 prototype compounds could be detectable in the plasma and urine samples, respectively, after oral administration of an SST extract (4 g·kg-1) in rats. No metabolites were observed in the rat samples. The findings of this work first unveiled the chemical complexity of SST and its absorbed components, which would be beneficial to understanding the therapeutic basis and quality control of SST.

Alleviating effects of Bushen-Yizhi formula on ibotenic acid-induced cholinergic impairments in rat.

This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases.

Bushen­Yizhi formula ameliorates cognition deficits and attenuates oxidative stress­related neuronal apoptosis in scopolamine­induced senescence in mice.

Bushen­Yizhi formula (BSYZ), a traditional Chinese medicine formula consisting of six herbs has been reported to possess a neuroprotective effect. The present study aimed to investigate the effects of BSYZ on learning and memory abilities, as well as oxidative stress and neuronal apoptosis in the hippocampus of scopolamine (SCOP)­induced senescence in mice, in order to reveal whether BSYZ is a potential therapeutic agent for Alzheimer's disease (AD). A high­performance liquid chromatography (HPLC) fingerprint was applied to provide a chemical profile of BSYZ. Extracts of BSYZ were orally administered to mice with SCOP­induced memory impairment for two weeks. The learning and memory abilities were determined by the Morris water maze test. The oxidant stress­related indices, such as activity of superoxide dismutase (SOD) and levels of glutathione (GSH) and malondialdehyde (MDA) were examined in hippocampus of SCOP­treated mice. The cell death ratio was assessed by TUNEL staining, while apoptotic­related proteins including Bcl­2 and Bax were determined by immuno-fluorescent staining and western blot analysis. Caspase­3 was determined by western blot analysis. Consequently, a chromatographic condition, which was conducted at 35˚C with a flow rate of 0.8 ml/min on the Gemini C18 column with mobile phase of acetonitrile and water­phosphoric acid (100:0.1, v/v), was established to yield common fingerprint chromatography under 203 nm with a similarity index of 0.986 within 10 batches of BSYZ samples. BSYZ at a dose of 2.92 g/kg significantly improved the cognitive ability, restored the abnormal activity of SOD and increased the levels of MDA and GSH induced by SCOP. Moreover, the neural apoptosis in the hippocampus of SCOP­treated mice was reversed by BSYZ by regulating the expression of Bcl­2, Bax and caspase­3. The results demonstrated that BSYZ had neuroprotective effects in SCOP­induced senescence in mice by ameliorating oxidative stress and neuronal apoptosis in the brain, supporting its potential in AD treatment.