Predicting acupuncture efficacy for major depressive disorder using baseline clinical variables: A machine learning study.

Acupuncture is a viable treatment option for major depressive disorder (MDD). However, its effectiveness varies among patients. This study aimed to develop a model to predict the efficacy of acupuncture therapy for MDD using machine learning and baseline clinical variables. A total of 124 patients with MDD from five research centers were included in our machine learning study. All patients underwent acupuncture treatment for 6 weeks and the efficacy of the treatment was evaluated using the Hamilton Depression Scale-17 (HAMD-17). The max-relevance and min-redundancy (mRMR) algorithm and Pearson correlation analysis were used for selecting 11 significant features from 26 baseline clinical variables for model training. We compared the performance of five machine learning models, including logistic regression, support vector machine, K-nearest neighbor, random forest, and XgBoost, in predicting the effect of acupuncture in relieving major depression. Among the five models, XgBoost performed the best with an area under the receiver operating characteristic curve (AUC) of 0.835, an accuracy of 0.730, a sensitivity of 0.670, a specificity of 0.774, and an F1 score of 0.751. The key predictive variables identified were anxiety score in the self-rating depression scale (SDS), the traditional Chinese medicine syndrome of deficiency in both heart and spleen, and body mass index (BMI). The study demonstrates that the developed model can help physicians predict the patients who will benefit from acupuncture treatment, which is of positive significance for improving the clinical efficacy of acupuncture on MDD.

Electroacupuncture Improves Depression-Like Behavior by Regulating the Abundance of Lactobacillus and Staphylococci in Mice.

BACKGROUND: Growing evidence suggests that gut microbiota can affect depression-like behavior, and electroacupuncture (EA) can regulate the composition and abundance of gut microbiota. At the same time, not a lot of research has been done on how EA affects gut microbiota to depression-like behavior. The objective of this study was to study the associated mechanisms by which EA exerts antidepressant effects by modulating gut microbiota. METHODS: Twenty-four C57BL/6 male mice were randomly divided into three groups, one group (n = 8) was the normal control group (NC). And the other two groups was chronic unpredictable mild stress for modeling + electroacupuncture group (CUMS + EA) (n = 8) and chronic unpredictable mild stress for modeling group (CUMS) (n = 8). Both CUMS and EA groups were subjected to 28 days of CUMS, but only the EA group received an additional 14 days of EA procedure. Behavior tests were used to determine the antidepressant effect of EA. Sequencing of the 16S ribosomal RNA (rRNA) gene was applied to examine alterations in the intestinal microbiome between groups. RESULTS: The findings were compared to those of the NC group, the sucrose preference rate and the total distance of Open Field Test (OFT) in CUMS group decreased, the abundance of Lactobacillus decreased, while the abundance of staphylococci increased. After the intervention of EA, the sucrose preference index and the total distance of OFT increased, the abundance of Lactobacillus increased, while the abundance of staphylococci decreased. CONCLUSIONS: These findings indicated EA may play an antidepressant effect by adjusting the abundance of Lactobacillus and staphylococci.

Dopaminergic signaling in prefrontal cortex contributes to the antidepressant effect of electroacupuncture: An iTRAQ-based proteomics analysis in a rat model of CUMS.

Electroacupuncture (EA) is used as an adjunctive treatment for depression. This study was conducted to evaluate the efficacy and mechanisms of EA in the depressive rat model induced by chronic unpredictable mild stress (CUMS) in male adult Wistar rats. The underlying mechanisms were explored by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the proteins in the prefrontal cortex (PFC), and observing the number of the PFC neurons stained with hematoxylin and eosin (H&E) and synaptic morphological changes under transmission electron microscopy (TEM). The results showed that EA plus paroxetine (EA + Par) for 1 week significantly relieved depression-like anhedonia symptoms and improved anxiety-like behavior, accompanied by the improvements in synaptic morphology and a significant increase of PFC neurons. Moreover, EA or paroxetine alone significantly alleviated anhedonia symptoms after 2 weeks of intervention. Additionally, iTRAQ analysis showed that dopaminergic signaling was significantly altered in CUMS rats after 1 week of EA treatment. As the critical enzyme of this pathway, aromatic-l-amino-acid decarboxylase (DDC) was significantly upregulated after the treatment with EA + Par for 1 week. These findings suggested that the dopaminergic signaling pathway in PFC may be involved in the antidepressant mechanisms of EA.

Scalp acupuncture enhances local brain regions functional activities and functional connections between cerebral hemispheres in acute ischemic stroke patients.

This study aimed to explore the changes in functional connections between cerebral hemispheres and local brain regions functional activities in patients with acute ischemic stroke (AIS) treated with International Standard Scalp Acupuncture (ISSA). Thirty patients with middle cerebral artery AIS in the dominant hemisphere were selected and randomly divided into two groups such as the control group and the scalp acupuncture group, with 15 patients in each group. Patients in the control group were treated with conventional Western medicine, while patients in the scalp acupuncture group received ISSA (acupuncture at the parietal midline [MS5], acupuncture at the left anterior parietotemporal oblique line [MS6] and acupuncture at the left posterior parietotemporal oblique line [MS7]) for one course of treatment. All patients were evaluated for treatment efficacy and received whole brain resting state functional magnetic resonance imaging (Rs-fMRI) scan before and after treatment. The observational indicators included: (a) the National Institutes of Health Stroke Scale (NIHSS) scores and the simplified Fugl-Meyer Assessment (SFMA) scores; (b) analyses of the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and voxel-mirrored homotopic connectivity (VMHC). The results showed a significant difference in the NIHSS scores before and after treatment in the scalp acupuncture group compared with the control group (p < .05), indicating that patients improved better after scalp acupuncture treatment. Compared with the control group, the VMHC, ALFF and ReHo values in the scalp acupuncture group increased after treatment. The VMHC values increased in the brain regions dominated by bilateral BA6 and BA8; the ALFF values increased in the left BA39 and the adjacent superior temporal gyrus and middle temporal gyrus; and the ReHo values increased in the brain regions extending from left middle temporal gyrus (including BA21) to BA37, and the brain regions extending from the left BA40 and angular gyrus to BA7. The present study indicated that scalp acupuncture can specifically strengthen the functional activities of the brain regions related to sensory integration, language processing and motor coordination in the middle aged and elderly patients with AIS of the dominant cerebral hemisphere, and can strengthen bilateral frontal lobe motor control. This study may provide a scientific basis for the clinical application of ISSA treatment in patients with AIS, and may also provide a preliminary research basis for further animal experiments.

The Role of Ophiopogonin D in Atherosclerosis: Impact on Lipid Metabolism and Gut Microbiota.

Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in Ophiopogon japonicus, is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE[Formula: see text] mice on the development of atherosclerosis and gut microbiota. To investigate the potential ability of OPD to alleviate atherosclerosis, 24 eight-week-old male ApoE[Formula: see text] mice (C57BL/6 background) were fed a high-fat diet (HFD) for 12 weeks, and 8 male C57BL/6 mice were fed a normal diet, serving as the control group. ApoE[Formula: see text] mice were randomly divided into the model group, OPD group, and simvastatin group ([Formula: see text]= 8). After treatment for 12 consecutive weeks, the results showed that OPD treatment significantly decreased the plaque formation and levels of serum lipid compared with those in the model group. In addition, OPD improved oral glucose tolerance and insulin resistance as well as reducing hepatocyte steatosis. Further analysis revealed that OPD might attenuate atherosclerosis through inhibiting mTOR phosphorylation and the consequent lipid metabolism signaling pathways mediated by SREBP1 and SCD1 in vivo and in vitro. Furthermore, OPD treatment led to significant structural changes in gut microbiota and fecal metabolites in HFD-fed mice and reduced the relative abundance of Erysipelotrichaceae genera associated with cholesterol metabolism. Collectively, these findings illustrate that OPD could significantly protect against atherosclerosis, which might be associated with the moderation of lipid metabolism and alterations in gut microbiota composition and fecal metabolites.

Electroacupuncture alleviated the depression-like behavior by regulating FGF2 and astrocytes in the hippocampus of rats with chronic unpredictable mild stress.

Studies have shown that basic fibroblast growth factor (FGF2) is a neurotrophic factor associated with depression. Electroacupuncture (EA) has been shown to be an effective treatment for depression. In the current study, we observed the effects of EA on hippocampal FGF2 and astrocytes, and further investigated the mechanism underlying antidepressant effect of EA. The chronic unpredictable mild stress (CUMS) method were selected to induce depressive-like behaviors of rats. Paroxetine is a commonly used antidepressant and was used as a positive control drug in this experiment. The male adult Sprague Dawley (SD) rats were randomized to four experimental groups (normal control group, CUMS group, EA group and paroxetine group, n = 10/group). EA intervention was administered once daily for 14 days at acupuncture points Baihui (GV20) and Yintang (GV29). Rats in the paroxetine group received daily paroxetine administered intragastrical. Behavioral test, immunohistochemistry (IHC), western blot (WB) and quantitative real-time PCR (qPCR) were conducted to evaluate the intervene effect and the changes of FGF2 and astrocyte marker (glial fibrillary acidic protein, GFAP). The results showed that EA and paroxetine could improve depression-like behavior in CUMS rats, and up-regulated the expression level of FGF2 in the hippocampus, increased GFAP protein expression and the mean optical density of GFAP-immunoreactive astrocyte (GFAP-ir astrocyte). Our findings have identified that EA could ameliorate depressive-like behaviors possibly by regulating the expression of FGF2 in the hippocampus, and the mechanism might be related to the effect of FGF2 on astrocytes.

Acupuncture at LR3 and KI3 shows a control effect on essential hypertension and targeted action on cerebral regions related to blood pressure regulation: a resting state functional magnetic resonance imaging study.

OBJECTIVE: The aim of this study was to investigate the effects of acupuncture at LR3 and KI3 on hypertension at different time points and on related cerebral regions using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: We randomly divided 29 subjects into two groups: Group A (receiving acupuncture at LR3 + KI3; 15 subjects) and group B (receiving acupuncture at LR3 and a sham location not corresponding to any traditional acupuncture point; 14 subjects). Acupuncture was performed. Blood pressure (BP) changes were recorded and analyzed using SPSS 20.0 statistical software. We used a 3.0T MRI scanner and standard GE 8 channel head coil to collect whole brain fMRI data in both groups. Data analysis and processing was based on the R2009a MATLAB platform. REST 1.8 software was used to analyze the whole brain amplitude of low-frequency fluctuation (ALFF). RESULTS: After acupuncture, a statistically significant reduction in BP at different time points was observed in group A. In group B, a statistically significant reduction was found only in diastolic blood pressure (DBP) and was not sustained. Acupuncture at LR3 + KI3 specifically affected brain areas involved in BP regulation, as well as those involved in auditory sense, speech, vision, movement and sensation. CONCLUSION: Acupuncture at LR3 + KI3 showed positive immediate and long-term effects on BP, particularly systolic blood pressure (SBP). After ALFF analysis, we concluded that LR3 + KI3 activates brain areas related to BP regulation. In addition, after acupuncture at LR3 + KI3, a highly targeted effect was observed in brain areas associated with BP. In addition, extracerebral areas involving vision, motion control, cognition and hearing were activated, which could potentially contribute to the mitigation of hypertensive complications in patients in an advanced stage of the disease.

Scalp Acupuncture Enhances the Functional Connectivity of Visual and Cognitive-Motor Function Network of Patients with Acute Ischemic Stroke.

DESIGN: A parallel-group randomized controlled trial. Participants. 30 hemiplegic patients with middle cerebral artery acute infarction of the dominant hemisphere. Interventions. 30 patients were divided into 2 groups randomly. 15 patients in the treatment group (TG) were treated with ISSA, needling at the parietal midline (MS5) and left anterior/posterior parietal-temporal oblique lines (MS6 and MS7), combined with western routine treatment. While another 15 patients in the control group (CG) received routine treatment only. Main Outcome Measures. (1) Functional connectivity (FC): patients received brain scan using 3.0 T MRI after the treatment for 1 week. Based on the Matlab2012a platform, SPM12 software and DPABI software were used to process the scanning data and finally the functional connectivity of the brain was obtained. (2) National Institute of Health Stroke Scale (NIHSS) score. RESULTS: The difference in the NIHSS score between the two groups of patients before and after treatment was statistically significant (tNIHSS = 2.225; PNIHSS = 0.038), indicating that TG had a better effect. Centered to the seed region of the left supplementary motor area (SMA) (-5.32, 4.85, 61.38), FC increased at the left middle cerebellar peduncle, left cerebellum posterior lobe (uvula and declive), vermis, fusiform gyrus, lingual gyrus, inferior occipital gyrus, calcarine, cuneus, precuneus, BA7, BA18 and BA19, etc. Centered to the seed region of the left parahippocampal gyrus (PG) (-21.17, -15.95, -20.70), FC increased at the left precuneus, inside-paracingulate, inferior parietal gyrus, paracentral lobule, BA5, BA6, BA7, and BA40, right median cingulate, precuneus, BA19, BA23, and BA31, etc. CONCLUSIONS: It is indicated that ISSA can regulate the brain functional connection in patients with middle cerebral artery acute infarction in the dominant hemisphere and specifically strengthen the connections between visual, cognitive, motor control, and planning-related brain regions, which may be related to the recovery of movement in the mechanism. This trial is registered with ChiCTR-IOR-15007672.

EA Ameliorated Depressive Behaviors in CUMS Rats and Was Related to Its Suppressing Autophagy in the Hippocampus.

Autophagy is confirmed to be involved in the onset and development of depression, and some antidepressants took effect by influencing the autophagic process. Electroacupuncture (EA), as a common complementary treatment for depression, may share the mechanism of influencing autophagy in the hippocampus like antidepressants. To investigate that, sixty Sprague-Dawley rats firstly went through chronic unpredictable mild stress (CUMS) model establishment, and 15 rats were assigned to a control group. After modeling, 45 successfully CUMS-induced rats were randomly divided to 3 groups: CUMS, selective serotonin reuptake inhibitor (SSRI), and EA groups (15 rats per group), to accept different interventions for 2 weeks. A sucrose preference test (SPT), weighing, and open field test (OFT) were measurement for depressive behaviors of rats. Transmission electron microscope (TEM), immunohistochemistry (IHC), and western blot analysis were used to evaluate the autophagic changes. After that, depression-like behaviors were successfully induced in CUMS models and reversed by SSRI and EA treatments (both p < 0.05), but these two therapies had nonsignificant difference between each other (p > 0.05). Autolysosomes observed through TEM in the CUMS group were more than that in the control group. Their number and size in the SSRI and EA groups also decreased significantly. From IHC, the CUMS group showed enhanced positive expression of both Beclin1 and LC3 in CA1 after modeling (p < 0.05), and the LC3 level declined after EA treatments, which was verified by decreased LC3-II/LC3-I in western blot analysis. We speculated that CUMS-induced depression-like behavior was interacted with an autophagy process in the hippocampus, and EA demonstrated antidepressant effects by partly inhibiting autophagy with a decreased number of autolysosomes and level of LC3 along with LC3-II/LC3-I.

Electroacupuncture improves synaptic plasticity by regulating the 5-HT1A receptor in hippocampus of rats with chronic unpredictable mild stress.

OBJECTIVES: To investigate the antidepressant effects of electroacupuncture (EA) on chronic unpredictable mild stress (CUMS) in rats, as well as the effects of EA on hippocampal neurons, synaptic morphology, and 5-hydroxytryptamine (HT) receptor expression. METHODS: Forty adult male Wistar rats were randomly divided into normal control, CUMS, EA, and paroxetine groups. CUMS modeling was performed for 21 days, followed by 14 days of intervention: rats in the EA group underwent stimulation of GV20 and GV29 acupuncture points for 30 minutes daily; rats in the paroxetine group were administered paroxetine daily. Behavioral tests, transmission electron microscopy, western blotting, and real-time quantitative polymerase chain reaction were used to evaluate the effects of the intervention. RESULTS: EA treatment reversed the behavioral changes observed in rats due to CUMS modeling; it also improved the pathological changes in organelles and synaptic structures of hippocampal neurons, and upregulated the protein and mRNA expression levels of 5-HT1A receptor. There were no significant differences in 5-HT1B receptor protein and mRNA expression levels among the groups. CONCLUSIONS: EA treatment can alleviate depression-like symptoms in CUMS rats. The underlying mechanism may include promoting the expression of 5-HT1A receptor mRNA and protein, thereby improving synaptic plasticity in the hippocampus.

Modulatory effect of International Standard Scalp Acupuncture on brain activation in the elderly as revealed by resting-state fMRI.

The specific mechanisms by which acupuncture affects the central nervous system are unclear. In the International Standard Scalp Acupuncture system, acupuncture needles are applied at the middle line of the vertex, anterior parietal-temporal oblique line, and the posterior parietal-temporal oblique line. We conducted a single-arm prospective clinical trial in which seven healthy elderly volunteers (three men and four women; 50-70 years old) received International Standard Scalp Acupuncture at MS5 (the mid-sagittal line between Baihui (DU20) and Qianding (DU21)), the left MS6 (line joining Sishencong (EX-HN1) and Xuanli (GB6)), and the left MS7 (line joining DU20 and Qubin (GB7)). After acupuncture, resting-state functional magnetic resonance imaging demonstrated changes in the fractional amplitude of low frequency fluctuations and regional homogeneity in various areas, showing remarkable enhancement of regional homogeneity in the bilateral anterior cingulate, left medial frontal gyrus, supramarginal gyrus, right middle frontal gyrus, and inferior frontal gyrus. Functional connectivity based on a seed region at the right middle frontal gyrus (42, 51, 9) decreased at the bilateral medial superior frontal gyrus. Our data preliminarily indicates that the international standard scalp acupuncture in healthy elderly participants specifcally enhances the correlation between the brain regions involved in cognition and implementation of the brain network regulation system and the surrounding adjacent brain regions. The study was approved by the Ethics Committee of the China-Japan Union Hospital at Jilin University, China, on July 18, 2016 (approval No. 2016ks043).

Electroacupuncture Improves Antidepressant Effects in CUMS Rats by Protecting Hippocampal Synapse and Mitochondrion: An Ultrastructural and iTRAQ Proteomic Study.

Electroacupuncture (EA) is considered a complementary therapy for depression. Trials also found that EA has additive benefits when combined with medication compared with medication alone. It is revealed that EA restores altered hippocampal synaptic plasticity in depressed brain. But precise molecular mechanism is poorly understood. Here, we evaluated the therapeutic effects of EA and EA combined with selective serotonin reuptake inhibitor (SSRI) on depressed (CUMS) rats. Then a new proteomics approach, isobaric tag for relative and absolute quantitation (iTRAQ), was used to explore the differential expressed synaptic protein in hippocampus between CUMS and EA-treated rats to identify the possible target molecular mechanism of its effects. We found that EA had additive benefit against depressive behaviors when combined with SSRI. Ultrastructure study on neuron showed significant change in postsynapse density (PSD) and mitochondrion. Through iTRAQ, it is found that synaptic and mitochondrial proteins were significantly changed after EA, consisting with ultrastructure study results. These findings suggest that EA improves antidepressant performance in depressed rats through protecting synaptic and mitochondrial functions in hippocampus.

Manual or electroacupuncture as an add-on therapy to SSRIs for depression: A randomized controlled trial.

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants, however, only around 60% of patients could benefit from them. Acupuncture is supported by insufficient evidence to help with symptom relieving and SSRIs tolerance. This pragmatic randomized controlled trial compared SSRIs alone versus SSRIs together with manual acupuncture (MA) or electroacupuncture (EA) in moderate to severe depressed patients. Patients were randomly allocated to receive MA + SSRIs (161), EA + SSRIs (160), or SSRIs alone (156) for six weeks, and then followed up for another four weeks. The primary outcome was response rate of the 17-item Hamilton Depression Scale (HAMD-17) at 6th week. The secondary outcomes were HAMD-17 (remission rate, early onset rate, total score), Self-Rating Depression Scale (SDS: total score), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS: total and domain scores), number of patients with adjusted dosage of SSRIs and adverse events (AEs). Both MA + SSRIs and EA + SSRIs were significantly better than SSRIs at 6th week on HAMD-17 response rate (RR = 1.21, 95% CI 1.04, 1.42, P = 0.013; RR = 1.27, 95% CI 1.09, 1.48, P = 0.0014), HAMD-17 early onset rate (P < 0.0001), HAMD-17 and SDS total scores (P < 0.05), CGI (P < 0.01), SERS total score (P < 0.01), number of patients with increased dosage of SSRIs (P < 0.01). For HAMD-17 remission rate, EA + SSRIs was significantly higher than SSRIs (P = 0.0083), while MA + SSRIs showed no significant difference at 6th week (P = 0.092). No unintended acupuncture-related severe AE was observed. This study identified that both MA and EA showed beneficial effects in addition to SSRIs alone in patients with moderate to severe depression, and were well tolerated. Clinical trials registration: ChiCTR-TRC-08000297.

Different Brain Activation after Acupuncture at Combined Acupoints and Single Acupoint in Hypertension Patients: An Rs-fMRI Study Based on ReHo Analysis.

BACKGROUND: Acupuncture is proved to be effective on hypertension by numerous studies and resting-state functional magnetic resonance imaging (Rs-fMRI) is a widely used technique to study its mechanism. Along with lower blood pressure, patients with hypertension receiving acupuncture also presented improvement in function of cognition, emotion, language, sematic sensation, and so on. This study was a primary study to explore the acting path of acupuncture at combined acupoints in stimulated brain areas related to such functions. METHODS: In this research, regional homogeneity (ReHo) was applied to analyze the Rs-fMRI image data of brain activities after acupuncture at LR3, KI3, and LR3+KI3 and to compare the differences of functional brain activities between stimulating combined acupoints and single acupoint under pathological conditions. A total of thirty hypertension patients underwent Rs-fMRI scanning before acupuncture treatment and then were randomly divided into three groups following random number table, the LR3 group (3 males and 7 females), the KI3 group (3 males and 7 females), and the LR3+ KI3 group (4 males and 6 females) for needling, respectively. When the 30-min treatment finished, they received a further Rs-fMRI scanning. The Rs-fMRI data before and after the acupuncture treatment were analyzed through ReHo. RESULTS: Compared with preacupuncture, respectively, ReHo values increased in Brodmann areas (BAs) 3, 18, and 40 and decreased in BAs 7 and 31 in LR3+ KI3 group. However, ReHo values only decreased in BA7 of KI3 group while the results showed no significant difference of brain regions in LR3 group between pre- and postacupuncture. Compared with LR3 group, LR3+KI3 group exhibited decreased ReHo values in BAs 7, 9, and 31. Meanwhile, compared with KI3 group, LR3+KI3 group exhibited increased ReHo values in the BAs 2, 18, 30, and 40 and decreased ReHo values in BA13. CONCLUSION: Combined acupoints of LR3 and KI3 could act on wider brain areas than the sum of single acupoints, whose functions include emotional processing, cognition, somatic sensation, spatial orientation, language production, and vision.

[Analysis of genotype and phenotype of SEC23B gene in a family affected with congenital dyserythropoietic anemia type II].

OBJECTIVE: To detect potential mutation in a family affected with congenital dyserythropoietic anemia type II (CDA II). METHODS: Targeted sequence capture and next-generation sequencing (NGS) were used to analyze the exons and exon-intron boundaries of the SEC23B gene in a clinically suspected CDA II patient. Genotypes of the relatives were validated by Sanger sequencing. Potential impact of amino acid substitution on the structure and function of SEC23B protein was predicted with MutationTaster and PolyPhen-2. The protein structure was predicted with SWISS-MODEL software. RESULTS: The proband was found to harbor double heterozygous mutations of the SEC23B gene, c.1727T>C (p.F576S) and c.1831C>T (p.R611W), which resulted in amino acid substitutions p.F576S and p.R611W. Both mutations were confirmed by Sanger sequencing. The sister of the proband was found to have carried c.1727T>C (p.F576S), while her father and son have carried c.1831C>T (p.R611W) mutation. In addition, the proband was detected to have carried c.211C>T (p.R71X) of the HFE gene, which resulted in substitution of arginine by a stop codon. The impact of above mutations on the structure or function of protein was predicted to be harmful. Splenectomy and iron chelation therapy have achieved effective improvement of anemia and iron overload. Computer simulation suggested that the mutations have altered the 3D structure of the SEC23B protein. CONCLUSION: The novel compound mutations of c.1727T>C and c.1831C>T of the SEC23B gene probably underlie the CDA II in the family, and there is a strong correlation between the genotype and phenotype.

Long-term acupuncture treatment has a multi-targeting regulation on multiple brain regions in rats with Alzheimer's disease: a positron emission tomography study.

The acute effect of acupuncture on Alzheimer's disease, i.e., on brain activation during treatment, has been reported. However, the effect of long-term acupuncture on brain activation in Alzheimer's disease is unclear. Therefore, in this study, we performed long-term needling at Zusanli (ST36) or a sham point (1.5 mm lateral to ST36) in a rat Alzheimer's disease model, for 30 minutes, once per day, for 30 days. The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning. Positron emission tomography images were processed with SPM2. The brain areas activated after needling at ST36 included the left hippocampus, the left orbital cortex, the left infralimbic cortex, the left olfactory cortex, the left cerebellum and the left pons. In the sham-point group, the activated regions were similar to those in the ST36 group. However, the ST36 group showed greater activation in the cerebellum and pons than the sham-point group. These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer's disease.

Cerebral Targeting of Acupuncture at Combined Acupoints in Treating Essential Hypertension: An Rs-fMRI Study and Curative Effect Evidence.

The study attempted to explore that the synergistic effect of acupoints combination is not a simple superposition of single acupoint's effect by comparing and analyzing the changes of blood pressure (BP), SF-36, and brain regions after acupuncture treatment. 47 patients were randomly divided into LR3+KI3 group, LR3 group, and KI3 group. Subjects received Rs-fMRI scan, BP measurement, and SF-36 questionnaires before and after treatment and short-term acupuncture treatment. After treatment, there were no significant differences in BP and SF-36 among 3 groups, compared to the case before treatment, SBP of 3 groups decreased, and DBP significantly decreased while vitality and mental health significantly increased in LR3+KI3 group. Both number and scopes of changes of brain regions in LR3+KI3 group were the largest, which mainly included BAs 3, 4, 8, 19, 21, 24, 32, 44, and 45. In conclusion, acupuncture at LR3+KI3 may auxiliarily reduce BP and improve the vitality and mental health of patients, and the changes of brain regions were related to somatesthesia, movement, vision, audition, emotion and mood, language, memory, etc. BAs 4, 9, 10, 24, 31, 32, and 46 may be the targeting brain areas of acupuncture in assisting hypotension. It is suggested that acupoints combination of LR3+KI3 maybe generates a synergistic effect, and it is not simple sum of single acupoint effect.

Acupuncture Decreases Blood Pressure Related to Hypothalamus Functional Connectivity with Frontal Lobe, Cerebellum, and Insula: A Study of Instantaneous and Short-Term Acupuncture Treatment in Essential Hypertension.

The therapeutic effects of acupuncture in decreasing blood pressure are ambiguous and underlying acupuncture in hypertension treatment has not been investigated. Our objective was to observe the change of quality of life and compare the differences in brain functional connectivity by investigating instantaneous and short-term acupuncture treatment in essential hypertension patients. A total of 30 patients were randomly divided into the LR3 group and sham acupoint group. Subjects received resting-state fMRI among preacupuncture, postinstantaneous, and short-term acupuncture treatment in two groups. Hypothalamus was selected as the seed point to analyze the changes in connectivity. We found three kinds of results: (1) There was statistical difference in systolic blood pressure in LR3 group after the short-term treatment and before acupuncture. (2) Compared with sham acupoint, acupuncture at LR3 instantaneous effects in the functional connectivity with seed points was more concentrated in the frontal lobe. (3) Compared with instantaneous effects, acupuncture LR3 short-term effects in the functional connectivity with seed points had more regions in frontal lobe, cerebellum, and insula. These brain areas constituted a neural network structure with specific functions that could explain the mechanism of therapy in hypertension patients by LR3 acupoint.

Evidence of a Synergistic Effect of Acupoint Combination: A Resting-State Functional Magnetic Resonance Imaging Study.

OBJECTIVE: This study aimed to find evidence of a synergistic effect of acupoint combinations by analyzing different brain regions activated after acupuncture at different acupoint combinations. METHODS: A total of 57 healthy subjects were randomly distributed into three groups: LR3 plus KI3 acupoints, LR3 plus sham acupoint, or LR3 alone. They underwent a magnetic resonance imaging scan before and after acupuncture. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values of different brain regions were analyzed to observe changes in brain function. RESULTS: ALFF and ReHo produced an activated area in the cerebellum posterior lobe after acupuncture at LR3 plus KI3 acupoints versus LR3 alone. ALFF and ReHo revealed altered activity in Brodmann area 10 (BA10), BA18, and brainstem pons after acupuncture at LR3 plus sham acupoint compared with at LR3 alone. A comparison of acupuncture at LR3 plus KI3 acupoints with LR3 plus sham acupoint demonstrated an increase in BA6 of ALFF and a downregulation of ReHo. CONCLUSIONS: The increased number of brain regions with altered brain activity after acupuncture at acupoint combinations versus a single acupoint are evidence of the synergistic effect of acupoint combinations. BA6 was significantly activated after acupuncture at LR3 plus KI3 acupoints compared with at LR3 plus sham acupoint, suggesting that BA6 is the specific region of synergistic effect of acupoint combinations of LR3 plus KI3 acupoints. Affected brain regions were different between acupuncture at LR3 plus sham acupoint and LR3 alone, which indicates that the sham acupoint may have some psychological effect. However, the specific mechanism of acupoint combinations requires further research.

Acupuncture Decreases NF-κB p65, miR-155, and miR-21 and Increases miR-146a Expression in Chronic Atrophic Gastritis Rats.

Acupuncture has been used to treat chronic atrophic gastritis (CAG) in traditional Chinese medicine (TCM) for centuries. In this study, we evaluated the effect of acupuncture at Zusanli (ST36), Zhongwan (CV12), and Pishu (BL20) acupoints on weight changes of rats, histological changes of gastric glands, and expressions changes of nuclear factor-kappa B (NF-κB) p65, microRNA- (miR-) 155, miR-21, and miR-146a in CAG rats induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) combined with irregular diet. Consequently, we found that acupuncture treatment elevated body weight of rats significantly when compared to the model group. By observing histological changes, we found that the acupuncture group showed better improvement of gastric mucosa injury than the model group. Our results also demonstrated upregulation of NF-κB p65, miR-155, and miR-21 in gastric tissue of CAG rats and a positive correlation between miR-155 and miR-21. Relatively, expression of miR-146a was downregulated and negative correlation relationships between miR-146a and miR-155/miR-21 in CAG rats were observed. Additionally, expressions of NF-κB p65, miR-155, and miR-21 were downregulated and miR-146a was upregulated after acupuncture treatment. Taken together, our data imply that acupuncture can downregulate NF-κB p65, miR-155, and miR-21 and upregulate miR-146a expression in CAG rats. NF-κB p65, miR-155, miR-21, and miR-146a may play important roles in therapeutic effect of acupuncture in treating CAG.