Acupuncture for emotional symptoms in patients with functional gastrointestinal disorders: A systematic review and meta-analysis.

BACKGROUND: Patients with functional gastrointestinal disorders (FGIDs) also often have emotional symptoms, such as anxiety and depression. The main drugs used for the treatment of FGIDs mainly target single gastrointestinal symptoms and are not effective in regulating emotional symptoms. Evidence has shown that acupuncture can relieve gastrointestinal symptoms in FGIDs patients, but there is no high-quality evidence to show that acupuncture can relieve psychological symptoms in these patients. OBJECTIVES: To systematically evaluate the clinical efficacy and safety of acupuncture for emotional symptoms in patients with FGIDs. METHODS: Randomized controlled trials (RCTs) published from database inception through July 31, 2021, were retrieved from three English-language databases (PubMed, the Cochrane Central Register of Controlled Trials, and Embase) and five Chinese-language databases (the China National Knowledge Infrastructure, Wanfang, VIP, Chinese Biomedical, and TCM Literature Analysis and Retrieval databases). RCTs that compared acupuncture with sham acupuncture and pharmacotherapy were included in this study. The score on the depression or anxiety scale after treatment were considered as primary outcomes. The 'meta' package (version 4.19-0) in RStudio 1.1.463 was used to analyse the data. RESULTS: A total of 2151 patients from 24 RCTs were included in this study. Compared with sham acupuncture, acupuncture was not significantly better at relieving anxiety (standardized mean difference [SMD] -0.35, 95% CI -1.05 to 0.33) and depression (SMD -0.32, 95% CI -0.71 to 0.07) symptoms. Compared with pharmacotherapy, acupuncture was significantly better at relieving anxiety (SMD -0.64, 95% CI -0.93 to -0.35) and depression (SMD -0.46, 95% CI -0.69 to -0.22) symptoms. CONCLUSIONS: This meta-analysis found that acupuncture can alleviate emotional symptoms in FGID patients better than pharmacotherapy. However, it is not clear whether this effect is based on the placebo effect, specific effect or nonspecific effect of acupuncture. The evidence should be proven by rigorously designed RCTs in the future. PROSPERO REGISTRATION NUMBER: CRD42021271899.

[Effect of umbilical moxibustion on phlegm damp constitution and intestinal flora].

OBJECTIVE: To observe the effect of umbilical moxibustion on phlegm damp constitution and intestinal flora, and explore the mechanism of umbilical moxibustion in improving phlegm damp constitution. METHODS: A total of 60 subjects with phlegm damp constitution were randomly divided into an observation group and a control group, 30 cases in each group. The control group was given TCM health guidance, such as diet and exercise; on the basis of the control group, umbilical moxibustion was applied in the observation group, 7 moxa cones each time, 2 times a week for 8 weeks. Before and after intervention, the indexes (transformation score of phlegm damp constitution, body mass, body mass index [BMI], waist circumference, hip circumference, heart rate and blood pressure) related to phlegm damp constitution were recorded in the two groups. The intestinal flora was detected with 16S rDNA sequencing technology in the two groups. RESULTS: After intervention, the transformation score of phlegm damp constitution, body mass, BMI, waist circumference and hip circumference were decreased compared before intervention in the observation group (P<0.001, P<0.01, P<0.05), the transformation score of phlegm damp constitution and waist circumference were decreased compared before intervention in the control group (P<0.001, P<0.05); the transformation score of phlegm damp constitution and waist circumference in the observation group were lower than the control group (P<0.001, P<0.05). After intervention, the relative abundance of Eubacterium hallii in the observation group was increased (P<0.01), the relative abundance of Blautia in the control group was decreased (P<0.05). CONCLUSION: Umbilical moxibustion may reshape the intestinal flora by up-regulating the relative abundance of Eubacterium hallii, thus improving phlegm damp constitution.

Acupuncture for Subthreshold Depression: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Subthreshold depression refers to a state of mental sub-health that has depressive symptoms but does not meet the diagnostic criteria for major depressive disorder. It is a strong risk factor for depression and is related to an increase in suicide and mortality. Studies suggest that acupuncture may be effective in the treatment of subthreshold depression, but no evidence has proven that the efficacy of acupuncture for subthreshold depression is a specific therapeutic effect or a placebo effect. METHODS: This will be a prospective, randomized, controlled, and double-blind study of 64 patients with subthreshold depression. They will be randomly assigned as verum or minimal acupuncture group members. Patients in the verum acupuncture group will receive acupuncture at the acupoints, and those in the minimal acupuncture group will receive minimal acupuncture at non-acupoints. The interventions will be delivered over an 8-week period. The primary outcome measure will be the Hamilton Depression Scale-17 (HAMD-17). The secondary outcome measures will be the 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalized Anxiety Disorder (GAD-7), and SF-12v2 Health Survey. The assessments will occur at baseline, 4 weeks, 8 weeks, and during a follow-up period. DISCUSSION: The protocol uses a randomized controlled trial to examine the effectiveness of acupuncture for subthreshold depression and to further study the mechanisms of its effect.

Jiaji (EX-B2)-Based Electroacupuncture Preconditioning Attenuates Early Ischaemia Reperfusion Injury in the Rat Myocardium.

BACKGROUND: Acupuncture preconditioning was able to reduce the extent of ischaemia reperfusion (I/R) injury. Previous studies have shown that electroacupuncture (EA) pretreatment at T4-T5 Jiaji (EX-B2) acupoints had cardioprotective effects against myocardial I/R injury. However, the molecular mechanism remains inconclusive. METHODS: Wistar rats were pretreated with electroacupuncture for 7 days at the Neiguan (PC6), T4-T5 Jiaji (EX-B2), Yanglingquan (GB34), and Quchi (LI11) acupoints, which belong to different meridians. Then, we investigated the genome-wide gene expression profiles of rats prestimulated at these acupoints after I/R injury. RESULTS: Our study revealed previously unknown cardioprotective roles of T4-T5 Jiaji (EX-B2) acupoints in the I/R progression. The extent of myocardial injury was significantly decreased in the Jiaji group compared with the I/R group. In addition, our data are among the first to link the EA preconditioning at Neiguan (PC6) acupoints and circadian rhythm in the I/R model. Also, for the first time, we explored the meridian and acupoint specificity involved in EA pretreatment at the heart meridian, in which Yanglingquan and Quchi acupoints were selected as the control group for heart-divergent-meridian and nonheart-meridian acupoints. CONCLUSIONS: The present study suggested that EA pretreatment at Jiaji alters genome-wide gene expression and protects the rat myocardium against I/R injury, which are most likely through neurohumoral regulation.

[Effect of "Jiaji" (EX-B2)-electroacupuncture preconditioning on expression of myocardial cytochrome P450 enzyme in rats with acute myocardial ischemia-reperfusion injury].

OBJECTIVE: To investigate the effect of "Jiaji"(EX-B2)-electroacupuncture(EA) preconditioning on structural changes of myocardium and expression of cytochrome P450 (CYP450) enzymes in acute myocardial ischemia-reperfusion injury (MIRI) rats. METHODS: Sixty male Wistar rats were randomly divided into sham operation, model, EX-B2, Neiguan (PC6), Yanglingquan(GB34) and Quchi (LI11) groups (n＝10 in each group). The MIRI model was established by occlusion of the descending anterior branch of the left coronary artery for 30 min, followed by reperfusion for 30 min. EA preconditioning (2 Hz/100 Hz, 1 mA) was respectively applied to EX-B2, PC6, GB34, and LI11 for 30 min, once daily for 7 days. Morphological changes of myocardium were observed by H．E. staining. The ultrastructure of myocardial cells was observed by transmission electron microscope (TEM). The protein expression levels of myocardial CYP450 (CYP1A1, CYP2B2, CYP2C11 and CYP4A2) were detected by Western blot. RESULTS: In MIRI rats, myocardial pathological changes as swollen, disorganized arrangement, and partially ruptured myocardial fibers with unclear limit and necrosis and infiltration of lots of inflammatory cells under microscope, and focal myofilament degeneration, dissolution and necrosis with interstitial edema, vague mitochondria with swelling and vacuolation, ruptured and disorganized arrangement of crests under TEM were found in the ischemic area, which was obviously milder in rats of both EX-B2 and PC6 groups. After modeling, the expression of myocardial CYP1A1 and CYP2B2 protein were significantly up-regulated in the model group relevant to the sham operation group (P<0.05). In EA preconditioning groups, the expression levels of CYP1A1 and CYP4A2 proteins in the EX-B2, PC6 and GB34 groups were obviously down-regulated (P<0.01), and those of CYP2B2 and CYP2C11 proteins in both EX-B2 and PC6 groups were markedly up-regulated relevant to the model group (P<0.01). Compared with the EX-B2 group, the expression levels of CYP1A1, CYP4A2 proteins in the LI11 group were significantly up-regulated (P<0.05), and CYP2B2, CYP2C11 proteins were significantly down-regulated (P<0.05). No significant differences were found between the model and sham operation groups in the expression levels of myocardial CYP2C11 and CYP4A2 proteins, between the LI11 and model groups in the expression of CYP1A1, CYP2B2, CYP2C11 and CYP4A2, between the GB34 and model groups in the expression of CYP2B2, CYP2C11 (all P>0.05)．. CONCLUSION: EA preconditioning at EX-B2 and PC6 can suppress MIRI induced up-regulation of myocardial CYP450 ω-hydroxylase CYP1A1 and CYP4A2 expression and further up-regulate the expression of myocardial epoxygenase CYP2B2 and CYP2C11 proteins in acute MIRI rats, thus playing a role in myocardial protection.

[Effect of "Jiaji"(EX-B 2)-electroacupuncture Preconditioning on Expression of Cytochrome P 450 Signaling Pathways in Myocardial Ischemia-reperfusion Rats].

OBJECTIVE: To investigate the effect of "Jiaji"(EX-B 2)-electroacupuncture(EA) preconditioning on the myocardium and expression of cytochrome P 450 signaling pathways of myocardial cells in myocardial ischemia-reperfusion injury(MI/RI) rats. METHODS: Sixty male Wistar rats were randomly divided into sham operation, model, Jiaji, Neiguan(PC 6), Yanglingquan(GB 34) and Quchi(LI 11) groups (n=10 in each group). MI/RI model was established by occlusion of the descen-ding anterior branch of the left coronary artery. EA preconditioning was respectively applied to EX-B 2, PC 6, GB 34 and LI 11 for 30 min, once daily for 7 days. The ECG-ST segment was detected before and after the modeling. The contents of serum creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) were detected by ELISA and microplate method separately. The expression levels of myocardial CYP 450 related genes cyp 1 a 1, cyp 2 b 2, cyp 2 c 11, cyp 4 a 2 were detected by Real-time PCR. RESULTS: Thirty minutes after ligation the changes of ECG-ST segment displacement of the Jiaji group and Neiguan group were signifi-cantly lower than that of the model group(P<0.01), and the change was significantly lower in the Neiguan group than in the model group(P<0.01) 30 minutes after reperfusion. Compared with the sham operation group, the activities of serum CK-MB and LDH were significantly increased in the model group(P<0.01). Compared with the model group, the activities of serum CK-MB and LDH were significantly decreased in the Jiaji, Neiguan and Yanglingquan groups (P<0.01). Compared with the Jiaji group, the activity of serum LDH was significantly increased in the Quchi group, while the activities of serum CK-MB were significantly increased in the Quchi and Yanglingquan groups (P<0.05). Compared with the sham operation group, the expression levels of myocardial cyp 1 a 1 and cyp 2 b 2 mRNAs were significantly higher in the model group(P<0.01), while the expression of cyp 2 c 11 mRNA was lower(P<0.01). Compared with the model group, the expression levels of cyp 1 a 1 and cyp 4 a 2 mRNAs were lower in the Jiaji, Neiguan and Yanglingquan groups (P<0.01), while the expressions of cyp 2 b 2 and cyp 2 c 11 mRNAs were higher(P<0.01). Compared with the Jiaji group, the expression of cyp 1 a 1 mRNA was lower in the Neiguan group, while the expression of cyp 2 b 2 mRNA was higher(P<0.05). CONCLUSIONS: EA preconditioning at Jiaji(EX-B 2) can reduce serum myocardial enzymes of myocardial ischemia-reperfusion rats, lower the ST segment of electrocardiogram, up-regulate myocardial CYP 450 epoxygenase cyp 2 b 2 and cyp 2 c 11 mRNAs expression, down-regulate ω-hydroxylase cyp 1 a 1 and cyp 4 a 2 mRNAs expression, thus play a role in myocardial protection.

[Progress on the Relationship Between the Regulation of Gastrointestinal System Function by Acupuncture and Central Nuclei].

Acupuncture has a good curative effect in the treatment of gastrointestinal system diseases, such as functional dyspepsia, ulcerative colitis, and constipation. The central nuclei which are involved in the mechanism of acupuncture in regulating the gastrointestinal system have become a research hotspot in recent years. In the present paper, the authors summarized the effect of acupuncture and the central nervous system on gastrointestinal function regulation. It was found that the regulation of gastrointestinal function by acupuncture involved many brain regions such as the amygdala, paraventricular nucleus, locus coeruleus, raphe nucleus, and dorsal nucleus of the vagus nerve. Of these, the limbic brain region had the closest relation. However, the included studies were animal experiments, which involved less research on nuclear group interactions. The role of central nuclei in the regulation of gastrointestinal function by acupuncture is unclear. Thus, the introduction of more advanced brain imaging techniques to observe brain dysfunction of central nuclei and the relativity of acupuncture in regulating gastrointestinal function will be the focus in the future study, which will contribute to determining the effective mechanism of acupuncture and moxibustion.

Specific Correlation between the Hegu Point (LI4) and the Orofacial Part: Evidence from an fMRI Study.

Acupoint specificity is a foundational concept in acupuncture theory. It is closely related to the function of the acupoint. In this study, we sought to probe the central mechanisms of the specific correlation between LI4 and orofacial part in Bell's palsy patients. In total, 36 patients with left Bell's palsy were divided into three groups in random order, and each group received transcutaneous electrical acupoint stimulation (TEAS) at only one of three acupoints (LI4, ST6, and a sham point). A single-block fMRI design paradigm was applied to separately detect neural activity related to different stages of TEAS (prestimulation resting state, stimulation, and poststimulation resting state). Functional magnetic resonance imaging data were acquired during TEAS. There were extensive neuronal activities in the LI4 and ST6 groups and significant differences between stimulation at real and sham points. Brain regions were activated more by real acupoint TEAS than by sham point TEAS. Brain regions that were activated with LI4 and ST6 were broadly overlapping and adjacent. Our results provide supplementary neuroimaging evidence for the existence of acupoint specificity. These results may confirm the central mechanisms of the specific correlation between the Hegu point and the orofacial part.

Investigating the role of acute mental stress on endothelial dysfunction: a systematic review and meta-analysis.

Chronic stress is a known risk factor for both endothelial dysfunction and cardiovascular disease (CVD), but less is known of how acute mental stress affects the vasculature. In this systematic review and meta-analysis, we analyzed the impact of acute mental stress on flow-mediated dilation (FMD), an indicator of endothelial function. We searched the Medline, Cochrane, EMBASE, and ISI Web of Knowledge databases through May 2014, to identify publications in English-language journals. The primary outcome was the change in FMD from baseline to the time of measurement. We also assessed the risk of bias and the heterogeneity of included studies. Our search identified eight prospective studies, which displayed significant heterogeneity. Four studies measured FMD while the subject was performing the task; six measured FMD after the task had been completed. The total number of participants was 164. The pooled results indicate that FMD did not change significantly while the task was being performed (pooled difference in means: -0.853; 95 % confidence interval (CI), -3.926/2.220; P = 0.586); however, FMD measured after the task was completed was significantly less than baseline (pooled difference in means: -2.450; 95 %CI, -3.925/-0.975; P = 0.001). In conclusions, our findings provide evidence that an acute stressful experience has a delayed, negative impact on the function of the endothelium. Repeated exposure to short-term stress may lead to permanent injury of the vasculature. Therefore, assessment of patients' exposure to both repeated acute mental stress and chronic stress may be useful in determining their risk of developing CVD.

[Study on "Hegu (LI 4) regulates face and mouth" based on palmomental reflex].

OBJECTIVE: To explore the correlation between hand and face-mouth, so as to provide nerve reflex basis for the theory "Hegu (LI 4) regulates face and mouth". METHODS: Seven hundred and sixty-three participants who met the inclusive criteria were divided into different age groups. The skin around participants' thenar eminence was gently scraped to be observed whether there was an involuntary movement around the face or mouth, which was palmomental reflex. The results of palmomental reflex were recorded. RESULTS: The total occurrence rate of palmomental reflex was 46.26%. For those who were 0 to 1 years old, the palmomental reflex was all positive; for those who were 21 to 36 years old, the positive rate was 20.45%, which was the lowest; for those who were 65 to 85 years old, more than half of them were positive. The majority of those who were 0 to 2 years old were bilateral positive palmomental reflex, while the majority of those who were 65 to 85 years old were unilateral positive palmomental reflex. CONCLUSION: There is a certain connection between hand and face-mouth. The occurrence rate of palmomental reflex changes from high to low over age increasing, and then changes from low to high with the aging, presenting a "high-low-high" U-shaped curve, which is possible related to the growth and recession of nervous system.

Elevated PIVKA-II is associated with early recurrence and poor prognosis in BCLC 0-A hepatocellular carcinomas.

BACKGROUND: To investigate the prognostic value of serum PIVKA-II (prothrombin induced by the absence of vitamin K or antagonist-II) in BCLC (Barcelona Clinic Liver Cancer) 0-A hepatocellular carcinoma (HCC) patients after curative resection. MATERIALS AND METHODS: Preoperative sera were collected from 140 patients with BCLC 0-A HCCs undergoing curative resection during 2011-2012 in Zhongshan Hospital. Follow-up ended on November 2013. ELISA was used to detect the serum concentrations of preoperative PIVKA-II. The prognostic value of PIVKA-II and other clinicopathological factors was analyzed by the Kaplan-Meier method and the multivariate Cox proportional hazards model. RESULTS: During follow-up, 39 of 140 patients suffered recurrence and the 1-year recurrence rate was 27.9%. The high-PIVKA-II expression group had lower 1-year time to progression (TTP) compared with the low-expression group (54.8% vs 20.2%, p<0.001). Patients with high preoperative PIVKA-II expression showed a relatively higher risk of developing postoperative recurrence than those with low expression in the low-recurrence-risk subgroups, including α-fetoprotein ≤400ng/mL (45.4% vs 16.7%; p=0.006), tumor size ≤5 cm (54.2% vs 18.1%; p<0.001), single tumor (56.0% vs 19.1%; p<0.001), absence of satellite lesions (53.3% vs 19.8%; p=0.001), absence of vascular invasion (52.6% vs 14.9%; p=0.002), and Edmondson stage I/II (60.9% vs 20.3%; p<0.001). PIVKA-II was the strongest independent prognostic factor for TTP (hazard ratio, 2.877; 95% CI 1.524-5.429; p=0.001). CONCLUSIONS: Elevated PIVKA-II is associated with early recurrence of BCLC 0-A HCC after curative resection and can be considered a novel prognostic predictor.

[Effects of electroacupuncture at "Jiaji" (EX-B 2) on myocardial apoptosis and the expression of Bcl-2 and Bax in rats with ischemia-reperfusion injury].

OBJECTIVE: To explore the protective mechanism of acupuncture on myocardial ischemia-reperfusion injury. METHODS: Fifty Wistar rats were randomly divided into a sham-operation group, a model group, a Jiaji group , a Neiguan group and a Yanglingquan group, 10 rats in each group. The model of myocardial ischemia-reperfusion injury was duplicated by ligating the left anterior descending coronary artery (LADCA) in the later four groups, and the LADCA was not ligated in the sham-operation group. The rats in the treatment groups were treated with electroacupuncture at "Jiaji" (EX-B 2), "Neiguan" (PC 6) and "Yanglingquan" (GB 34) on both sides, respectively, once a day for 7 days. No interventions were produced in the sham-operation group and model group. Myocardial apoptosis were examined by the TUNEL method. The expressions of Bcl-2 and Bax proteins were measured by immunohistochemical method. RESULTS: Apoptosis index(AI) was significantly lower in the Jiaji group, Neiguan group and sham-operation group compared with model group (P < 0.01). Compared with the sham-operation group, AI were significantly increased in other groups (all P < 0.01). There was no significant difference in AI between Jiaji and Neiguan group (P > 0.05). Compared with the model group, the expression of Bcl-2 was significantly increased and Bax protein was significantly decreased in Jiaji group and Neiguan group (both P < 0.01). The expressions of Bcl-2 and Bax proteins were significantly increased in other groups compared with the sham-operation group (all P < 0.01). There was no significant difference in the expression of Bcl-2 and Bax proteins between Jiaji and Neiguan group (P > 0.05). CONCLUSION: Electroacupuncture at both Jiaji (EX-B 2) and Neiguan (PC 6) has protective effects on myocardial ischemia-reperfusion injury, and the mechanism is closely related to inhibiting myocardial apoptosis by adjusting the expression of Bcl-2 and Bax.

[Impacts of electroacupuncture at Lingtai (GV 10) and Shendao (GV 11) on premature heartbeat].

OBJECTIVE: To observe the specific clinical efficacy of electroacupuncture at Lingtai (GV 10) and Shendao (GV 11) on premature heartbeat. METHODS: Seventy-two cases of premature heartbeat were randomized into an observation group and a control group. In the observation group, electroacupuncture was applied at Lingtai (GV 10) and Shendao (GV 11). In the control group, electroacupuncture was applied at bilateral Xuanzhong (GB 39). The treatment was given once a day and 10 times made one session in both groups. Respectively, the dynamic electrocardiogram detection was done before treatment and after one session of treatment in each group. RESULTS: The total effective rate was 47.1% (16/34) in the observation group and 6.5% (2/31) in the control group. The efficacy in the observation group was superior to that in the control group, presenting the statistical significant difference in comparison (P < 0.05). CONCLUSION: Electroacupuncture at Lingtai (GV 10) and Shendao (GV 11) has specific clinical efficacy on premature heartbeat.

[Mast cell and substance P are involved in the process of acupoint sensitization induced by acute gastric mucosal injury].

OBJECTIVE: To observe changes of mast cells (MCs) number and morphology, and substance P (SP) expression in Evans blue (EB) extravasated region around acupoint "Pishu" (BL 20) and "Weishu" (BL 21) after acute gastric mucosal injury (AGMI) so as to investigate the mechanism underlying visceral problems-induced acupoint activation. METHODS: Thirty adult Wistar rats were randomly divided into normal control (n = 15) and AGMI groups (n = 15). AGMI model was duplicated by perfusing the rats with 0.5 mol/L HCl (1 mL/100 g) after fasting for 20 h. Five hours after AGMI, the rats were treated by tail-intravenous injection of EB dye (5 mg/100 g, 50 mg/mL in normal saline) for inducing dye-plasma extravasation in the skin around BL 20, BL 21 regions, etc. at the back. The rats of the normal control group were treated with tail-intravenous injection of 0.9% NaCl. The skin and subcutaneous tissues (2 mmx 2 mm) of extravasated EB dye points (BL 20 or BL 21 region) and those 2 mm lateral to the extravasated EB dye points in the model group and the corresponding points in the normal control group were sampled (followed by fixing them in 4% paraformaldehyde), sectioned and stained by toluidine blue (for labeling MCs). The expression of SP in the extravasated EB dye skin and subcutaneous tissues was detected by immunohistochemistry (n = 5) and western blot (n = 5) respectively. The number of MCs in these samples was counted and the degranulation rate of MCs calculated. RESULTS: The total number of MCs and the number of degranulated MCs were significantly more in the EB extravasation points (corresponding to BL 20/BL 21 area) of AGMI group than those in the control spots of AGMI group and than those in the normal control group (P < 0.05, P < 0.001). The degranulation rate of MCs was significantly higher in the EB extravasation points of AGMI group than those in the control spots of AGMI group and in the normal control group (P < 0.01). In comparison with normal control group, the SP expression level was increased consideraly in the control spots of AGMI group and AGMI group (P < 0.01). CONCLUSION: After AGMI, the numbers of MCs and the degranulated MCs, and the SP expression level in BL 20/BL 21 area were increased significantly, suggesting an involvement of MCs and SP in the process of AGMI-induced activation of acupoints.