BACKGROUND: Over 65 million people have long COVID. Evidence for using Chinese herbal medicine (CHM) to treat long COVID is growing. A systematic review of evidence for guiding clinical decision is warranted. OBJECTIVE: To examine the effects and safety of CHM in alleviating the severity of dyspnea, fatigue, exercise intolerance, depression, anxiety and insomnia in long COVID adults based on registered randomized clinical trials (RCT). SEARCH STRATEGY: World Health Organization International Clinical Trials Registry Platform and Chinese Clinical Trial Registry were searched for registered trial protocols from database inception to February 10, 2023. English (PubMed, Embase, AMED and CINAHL) and Chinese databases (CNKI, Wanfang Data and CQVIP) were then searched to identify relevant publications from December 2019 through April 6, 2023. INCLUSION CRITERIA: Registered RCTs that compared the effects of Chinese herbal medicines or Chinese herbal formulas against a control treatment (i.e., the placebo or usual care) in adults with persistent symptoms of long COVID. The primary outcome of dyspnea, and secondary outcomes of fatigue, exercise intolerance, depression, anxiety and insomnia were measured using validated tools at the end of the treatment. DATA EXTRACTION AND ANALYSIS: Data were extracted, and eligible RCTs were evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations, Assessment, Development and Evaluations independently by two researchers. Effect sizes were estimated by random-effects modelling and mean difference (MD). Heterogeneity between trials was quantified by I². RESULTS: Among the 38 registered clinical trials we identified, seven RCTs (1,519 patients) were included in the systematic review. One RCT had a low overall risk of bias. Compared to the control, CHM reduces dyspnea on the Borg Dyspnea Scale score (MD = -0.2, 95% confidence interval [CI] = -0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD = -0.48, 95% CI = -0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD = -6.00, 95% CI = -7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD = -6.10, 95% CI = -7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD = -4.86, 95% CI = -12.50 to 2.79) with moderate certainty. Meta-analysis of two RCTs (517 patients) showed that CHM clinically improves exercise intolerance by increasing 6-minute walking distance (MD = -15.92, 95% CI = -10.20 to 42.05) with substantial heterogeneity (I² = 68%) and low certainty. CONCLUSION CHM is associated with a post-treatment clinical reduction in depression and anxiety in long COVID adults, compared to the control, but it does not have a strong treatment effect on dyspnea and insomnia. Effects of CHM on exercise intolerance and fatigue are uncertain, and the safety of using CHM remains questionable. Please cite this article as: Tsang MS, Zhou IW, Zhang AL, Xue CC. Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials. J Integr Med. 2025; 23(2): 126-137.
Humans ; Dyspnea/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; COVID-19/complications* ; Fatigue/drug therapy* ; SARS-CoV-2 ; Anxiety/drug therapy* ; Depression/drug therapy* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Betacoronavirus

OBJECTIVE: To observe the clinical efficacy of acupuncture combined with bamboo-based medicinal moxibustion in the treatment of chronic insomnia complicated with mild depressive state. METHODS: A total of 60 patients with chronic insomnia complicated with mild depressive state were randomly divided into an observation group and a control group, 30 cases in each group. The control group was treated with acupuncture at bilateral Zhaohai (KI6), Shenmen (HT7), Sanyinjiao (SP6), Anmian (Extra) and Sishencong (EX-HN1), Baihui (GV20), etc. The observation group was treated with bamboo-based medicinal moxibustion based on the treatment in the control group, on the abdomen，Shenque (CV8), Guanyuan (CV4), Zhongwan (CV12) and bilateral Tianshu (ST25) were selected , on the back, the acupoints of governer vessel from Dazhui (GV14) to Yaoshu (GV2) were selected. Both groups were treated once every other day, 3 times a week for 4 weeks. The Pittsburgh sleep quality index (PSQI) score, Hamilton depression scale-17 (HAMD-17) score, insomnia severity index (ISI) score, fatigue assessment instrument (FAI) score before and after treatment and after 2 weeks of treatment completion (follow-up) were observed in the two groups, and the serum level of γ-aminobutyric acid (GABA) before and after treatment was detected in the two groups, and the clinical efficacy and safety were evaluated. RESULTS: After treatment and in the follow-up, the sub-item scores and total scores of PSQI in both groups were reduced compared with those before treatment (P<0.001); except for the score of daytime dysfunction in the follow-up, the scores of sleep quality, sleep duration, daytime dysfunction, and total scores of PSQI in the observation group were lower than those in the control group (P<0.05). After treatment and in the follow-up, the HAMD-17, ISI and FAI scores in both groups were reduced compared with those before treatment (P<0.001); the scores in the observation group were lower than those in the control group (P<0.05). After treatment，the serum levels of GABA in both groups were increased compared with those before treatment (P<0.05); the level in the observation group was higher than that in the control group (P<0.05). The total effective rate of treating chronic insomnia in the observation group was 96.7% (29/30), which was higher than 80.0% (24/30) in the control group (P<0.05); and the total effective rate of improving mild depressive state was 93.3% (28/30), which was higher than 66.7% (20/30) in the control group (P<0.001). During the treatment period, no serious adverse reactions occurred in both groups. CONCLUSION Acupuncture combined with bamboo-based medicinal moxibustion has definite efficacy in the treatment of chronic insomnia complicated with mild depressive state, and has synergistic efficacy in improving sleep quality, sleep duration, daytime dysfunction and depressive state, its action mechanism may be related to the increase of serum level of GABA.
Humans ; Moxibustion ; Sleep Initiation and Maintenance Disorders/therapy* ; Male ; Female ; Middle Aged ; Adult ; Depression/therapy* ; Acupuncture Therapy ; Combined Modality Therapy ; Treatment Outcome ; Aged ; Young Adult ; Acupuncture Points

This paper introduces FU Wenbin's clinical experience in treatment of post-stroke depression with holistic therapy of acupuncture and moxibusiton for Shugan Tiaoshen (soothing the liver and regulating the mind). In pathogenesis, post-stroke depression is associated with the loss of the mind control and the failure of the liver in maintaining the free flow of qi. In treating principle, soothing the liver qi and regulating the mind are equally important, and the holistic regulation is applicable with the combination of multiple therapies. During treatment, the four-gate points are stimulated at first to promote liver qi flowing, the acupoints of the conception vessel and the governor vessel (e.g. Zhongwan [CV12], Guanyuan [CV4], Baihui [GV20], Yintang [GV24⁺]) are combined to regulate the mind and regain the consciousness. The conditions of illness are differentiated in terms of excess and deficiency, and the point prescription is modified accordingly. Refined moxibustion is applied specially at Fengchi (GB20), Fengfu (GV16) and Wangu (GB12) to warm meridians, strengthen yang and nourish the mind. In the last step of treatment, shallow needling techniques, such as the pricking and bloodletting, intradermal needling and auricular acupuncture, are used to consolidate the curative effect.
Humans ; Acupuncture Therapy ; Depression/etiology* ; Stroke/psychology* ; Female ; Male ; Middle Aged ; Acupuncture Points ; Moxibustion ; Aged ; Adult

OBJECTIVE: To observe the clinical effect of acupuncture and moxibustion combined with umbilical therapy on anxiety and depression in patients with neurogenic bladder (NB) after spinal cord injury (SCI). METHODS: Thirty cases of NB after SCI with anxiety and depression were selected and treated with acupuncture and moxibustion combined with umbilical therapy. Acupuncture was applied at Baihui (GV20), Yintang (GV24⁺), Sanyinjiao (SP6), Shenmen (HT7), Hegu (LI4), Taichong (LR3), once a day, continuous treatment for 4 weeks. Ginger moxibustion was applied at the bladder meridian of foot taiyang and governor vessel, once a day, continuous treatment for 4 weeks. In treatment of umbilical therapy, Chaihu (Radix Bupleuri), Yujin (Radix Curcumae), Rougui (Cortex Cinnamomi) were ground and mixed with the same amount of honey, put into the application, and the application was placed on the navel after filling the navel with fine salt, once a day for 4 weeks. Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, urodynamic indexes (maximum urinary flow rate [Qmax], maximum detrusor pressure [Pdet-max], residual urine volume [RUV]), neurogenic bladder symptom score (NBSS), urinary symptom distress scale (USDS) score were compared before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the scores of HAMA, HAMD, NBSS, USDS and RUVwere lower than those before treatment (P<0.05), and Qmax and Pdet-max were higher than those before treatment (P<0.05). The total effective rate was 93.3 (28/30). CONCLUSION Acupuncture and moxibustion combined with umbilical therapy can effectively relieve anxiety and depression symptoms, improve urination disorders in patients with NB after SCI.
Humans ; Moxibustion ; Male ; Female ; Adult ; Middle Aged ; Acupuncture Therapy ; Spinal Cord Injuries/psychology* ; Depression/etiology* ; Anxiety/etiology* ; Urinary Bladder, Neurogenic/etiology* ; Young Adult ; Aged ; Combined Modality Therapy ; Acupuncture Points

OBJECTIVE: To observe the clinical efficacy of heat-sensitive moxibustion robot for improving the depressive state of methamphetamine addicts during withdrawal period. METHODS: A total of 60 patients with methamphetamine addiction accompanied with depressive state were randomly divided into an observation group (40 cases, 4 cases dropped out) and a control group (20 cases, 2 cases dropped out). The control group received routine health education and addiction treatment in compulsory isolation drug rehabilitation center. On the basis of the treatment in the control group, in the observation group, the heat-sensitive moxibustion robot was used to locate sensitive points at the Shenque (CV8) and Danzhong (CV17), and dual-point sparrow-pecking moxibustion was delivered for 60 min per session. The moxibustion therapy was performed 4 times in the 1st week, 3 times in the 2nd and 3rd weeks respectively, and 2 times in the 4th week, for 12 times totally. The scores of Hamilton depression scale (HAMD), self-rating depression scale (SDS), visual analogue scale (VAS) for drug craving, Hamilton anxiety scale (HAMA), self-rating anxiety scale (SAS), and Pittsburgh sleep quality index (PSQI) were observed before treatment, at the end of the 2nd and 4th weeks of treatment, and 4 weeks after the treatment completion (follow-up) in the two groups. RESULTS: At each time point after treatment, in the observation group, the HAMD, VAS, HAMA and PSQI scores were decreased compared with those before treatment (P<0.01, P<0.001); at the end of the 4th week of treatment and in follow-up, the SDS and SAS scores were decreased compared with those before treatment (P<0.001, P<0.01). Compared before treatment, there were no significant differences in the above scores at each time point after treatment in the control group (P>0.05). In the observation group, at each time point after treatment, the HAMD and VAS scores were lower than those in the control group (P<0.01, P<0.001, P<0.05); at the end of the 4th week of treatment and in follow-up, the SDS and HAMA scores were lower than those in the control group (P<0.05, P<0.001); at the end of the 4th week of treatment, the PSQI score was lower than that in the control group (P<0.01). CONCLUSION Heat-sensitive moxibustion robot effectively improves depression, anxiety and sleep quality, and reduces drug craving in methamphetamine addicts during withdrawal period.
Humans ; Moxibustion/methods* ; Male ; Adult ; Female ; Methamphetamine/adverse effects* ; Depression/therapy* ; Middle Aged ; Robotics ; Young Adult ; Amphetamine-Related Disorders/psychology* ; Acupuncture Points ; Substance Withdrawal Syndrome/psychology*

OBJECTIVE: To observe the effects of Tongdu Tiaoshen acupuncture (acupuncture for unblocking the obstruction in the governor vessel and regulating the spirit) on the depression-like behavior and the hippocampal neuronal ferroptosis mediated by solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway in depression rats, and explore the mechanism of this therapy for depression. METHODS: Of 30 male SD rats of SPF grade, 24 rats were selected. According to the random number table, they were divided into a normal group (n=8) and a modeling group (n=16). The rats in the modeling group were subjected to chronic unpredictable mild stress (CUMS) for 28 consecutive days to establish depression model. After modeling, 16 successfully-modeled rats were randomly divided into a model group and an acupuncture group, 8 rats in each one. In the acupuncture group, Tongdu Tiaoshen acupuncture was applied to "Dazhui"(GV14), "Shuigou" (GV26), "Baihui" (GV20) and "Shenting" (GV24). This intervention measure was deliveredonce a day, continuously for 6 days. The intervention discontinued on day 7, and was completed in 4 weeks. Before and after modeling, and after intervention completion, the behavioristics detection was performed using sucrose preference experiment and open field experiment. After intervention, using hematoxylin-eosin (HE) and Nissl staining, the morphology of hippocampal neurons was observed; with Western blot method, the protein expression of GPX4, SLC7A11, Ferritin and acyl-CoA synthetase long-chain family 4 (ACSL4) in hippocampal tissues was detected; with the real-time fluorescence quantitative PCR adopted, the mRNA expression of GPX4, SLC7A11, Ferritin and ACSL4 was detected; and using colorimetry, the hippocampal iron content was determined. RESULTS: After modeling, the sucrose preference rates, the total distance of movement, the standing times and the boxes of horizontal crossing in the model group and the acupuncture group were lower than those in the normal group (P<0.01). After the intervention, the sucrose preference rates, the total distance of movement, the standing times and the boxes of horizontal crossing in the acupuncture group were higher than those in the model group (P<0.01, P<0.05). Compared with the normal group, the number of necrotic cells increased and the number of Nissl bodies decreased in the model group; and when compared with the model group, the neuronal pyknosis and necrosis were ameliorated, the cells were arranged more regularly, the neuronal structure was clear, the matrix was dense, the blood vessels were enriched and the number of Nissl bodies increased in the acupuncture group. In comparison with the normal group, the relative expression of protein and mRNA of hippocampal GPX4, SLC7A11 decreased (P<0.01), it increased in the expression of hippocampal Ferritin and ACSL4 (P<0.01) in the model group. When compared with the model group, in the acupuncture group, the relative expression of protein and mRNA of hippocampal GPX4, SLC7A11 was elevated (P<0.01, P<0.05), it was dropped for hippocampal Ferritin and ACSL4 (P<0.01). In the model group, the hippocampal iron content was elevated when compared with that in the normal group (P<0.01); and it was reduced in the acupuncture group when compared with that in the model group (P<0.05). CONCLUSION Tongdu Tiaoshen acupuncture attenuates depression-like behaviors in the depression rats, which may be related to regulating SLC7A11/GPX4 pathway and inhibiting neuronal ferroptosis in the hippocampus.
Animals ; Ferroptosis ; Male ; Hippocampus/cytology* ; Rats, Sprague-Dawley ; Rats ; Depression/enzymology* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Acupuncture Therapy ; Neurons/metabolism* ; Humans ; Acupuncture Points ; Amino Acid Transport System y+/genetics* ; Glutathione Peroxidase/genetics*

OBJECTIVE: To observe the effects of Tongdu Tiaoshen acupuncture (for unblocking the obstruction in the governor vessel and regulating the spirit) on depression-like behavior and the hippocampal Endophilin A1/reactive oxygen species (ROS) pathway in the chronic unpredictable mild stress (CUMS) model rats, and explore the mechanism of this therapy for depression. METHODS: Forty-eight male SD rats of SPF grade were randomly divided into a normal group (n=12) and a modeling group (n=36). In the modeling group, CUMS was performed to establish depression model. The successfully-modeled rats were randomized into a model group, a Tongdu Tiaoshen acupuncture group (referred to as the acupuncture group), and a fluoxetine group, with 12 rats in each group. In the acupuncture group, "Baihui" (GV20), "Shenting" (GV24), "Shuigou" (GV26) and "Dazhui" (GV14) were stimulated with acupuncture. This intervention measure was delivered once a day, continuously for 6 days; it was discontinued on day 7 and was completed in 28 days. In the fluoxetine group, intragastric administration was done with fluoxetine solution (2.1 mg/kg), once a day, and for 28 consecutive days. Before and after modeling, and after intervention completion, the body mass, sucrose preference rate and the total distance of movement and the boxes of horizontal crossing in the open field experiment were observed in each group. After intervention, using HE staining, the hippocampal neuron morphology was observed; using Nissl staining, the hippocampal Nissl body number was counted. The hippocampal mitochondria was observed under transmission electron microscopy. The average fluorescence intensity of ROS in hippocampal was determined using flow cytometry. With Western blot method, the protein expression of Endophilin A1, growth associated protein 43 (GAP-43), and brain-derived neurotrophic factor (BDNF) in hippocampal was detected; and with RT-qPCR method, the mRNA expression of Endophilin A1, GAP-43, and BDNF was recorded. Using the immunofluorescence, the average fluorescence intensity of Endophilin A1, GAP-43, and BDNF in hippocampal tissue was determined. RESULTS: Compared with the normal group, in the model group, the body mass, sucrose preference rate, and the total distance of movement and the boxes of horizontal crossing in the open field experiment decreased (P<0.01); the hippocampal neuronal structure was unclear, the matrix was relatively loose, and the number of Nissl body decreased (P<0.01); mitochondrial structure was disarranged, the outer membrane was ruptured, mitochondrial cristae was irregular or missed; the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue increased (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and its average fluorescence intensity decreased (P<0.01). Compared with the model group, the acupuncture group and the fluoxetine group showed the increase in body mass, sucrose preference rate, the total distance of movement and the boxes of horizontal crossing in the open field experiment (P<0.05, P<0.01); the hippocampal neuronal structure became relatively clear, the matrix was relatively dense, and the number of Nissl body was elevated (P<0.01); mitochondrial structure got normal and disarranged slightly, the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue were reduced (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and the average fluorescence intensity rose (P<0.01, P<0.05). Compared with the fluoxetine group, the acupuncture group presented the increase in the average fluorescence intensity of ROS, the protein expression and the average fluorescence intensity of Endophilin A1, the protein expression of GAP-43 and the mRNA expression of BDNF (P<0.01, P<0.05), and the decrease of the protein expression and the average fluorescence intensity of BDNF, the mRNA expression of Endophilin A1, and the average fluorescence intensity of GAP-43 (P<0.01, P<0.05). CONCLUSION Tongdu tiaoshen acupuncture alleviates depression-like behaviors in CUMS model rats and protects hippocampal neurons, which may be related to suppressing Endophilin A1/ROS signaling pathway and attenuating oxidative stress reactions.
Animals ; Male ; Hippocampus/metabolism* ; Acupuncture Therapy ; Rats, Sprague-Dawley ; Rats ; Depression/psychology* ; Humans ; Reactive Oxygen Species/metabolism* ; Disease Models, Animal ; Acupuncture Points

OBJECTIVE: To observe the clinical effect of Tiaoshen Guben holistic therapy of acupuncture and moxibustion (holistic treatment with acupuncture and moxibustion by adjusting the mind and consolidating the root) on comorbidity of depression and insomnia. METHODS: Twenty-four patients with comorbidity of depression and insomnia were included and treated with Tiaoshen Guben holistic therapy of acupuncture and moxibustion. Acupuncture was applied to Baihui (GV20), Guanyuan (CV4), bilateral Neiguan (PC6), etc. The refined moxibustion therapy was delivered at Zhongwan (CV12), Qihai (CV6), bilateral Yongquan (KI1), etc. Subcutaneous embedding therapy with thumb-tack needle was adopted at bilateral Xinshu (BL15), bilateral Pishu (BL20), etc. The intervention was operated once every other day, 3 treatments a week, and for 6 consecutive weeks. Before and after treatment completion, and in 1 month after treatment, Pittsburgh sleep quality index (PSQI) and Hamilton's depression scale (HAMD-17) were adopted to assess sleep quality and depression symptoms in the patients, respectively. Before and after treatment completion, using functional magnetic resonance imaging (fMRI), the functional connectivity (FC) of locus coeruleus (LC) in brain regions was evaluated; and the levels of serum norepinephrine (NE), cortisol (CORT), adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) were detected. RESULTS: Compared with the scores before treatment, PSQI and HAMD-17 scores after treatment completion and in 1 month after treatment were reduced (P<0.01); and strengthened FC was revealed between the right LC and the pars opercularis of the left inferior frontal gyrus, as well as the lateral occipital lobe region. After treatment completion, serum NE was elevated (P<0.01), the levels of CORT, ACTH and CRH were reduced (P<0.01). Before and after treatment completion, the difference in FC between the right LC and the pars opercularis of the left inferior frontal gyrus was negatively correlated with the differences in PSQI score (r = -0.484, P = 0.016) and HAMD-17 score (r = -0.233, P = 0.027). CONCLUSION Tiaoshen Guben holistic therapy of acupuncture and moxibustion can effectively alleviate depression symptoms and improve sleep quality in the patients with comorbidity of depression and insomnia, which is obtained probably through reducing the levels of serum CORT, ACTH and CRH, increasing serum NE, strengthening the FC of the right LC with the pars opercularis of the left inferior frontal gyrus and the lateral occipital lobe region.
Humans ; Moxibustion ; Sleep Initiation and Maintenance Disorders/therapy* ; Male ; Female ; Middle Aged ; Adult ; Acupuncture Therapy ; Depression/complications* ; Aged ; Young Adult ; Acupuncture Points ; Comorbidity

Major depressive disorder (MDD) affects people all over the world, and yet, its etiology is complex and remains incompletely understood. In this review, we aim to assess recent advances in understanding depression and its regulation, as well as its interaction with circadian rhythms. Circadian rhythms are internalized representations of the periodic daily light and dark cycles. Accumulating evidence has shown that MDD and the related mental disorders are associated with disrupted circadian rhythms. In particular, depression has often been linked to abnormalities in circadian rhythms because dysregulation of the circadian system increases susceptibility to MDD. The fact that several rhythms are disrupted in depressed patients suggests that these disruptions are not restricted to any one rhythm but rather involve the molecular circadian clock core machinery. The sleep-wake cycle is one rhythm that is often disrupted in depression, which often leads to disturbances in other rhythms. The circadian disruptions manifested in depressed patients and the effectiveness and fast action of chronobiologically based treatments highlight the circadian system as a key therapeutic target in the treatment of depression. This review assesses the evidence on rising depression rates and examines their contributing factors, including circadian misalignment. We discuss key hypotheses underlying depression pathogenesis, potential etiology, and relevant animal models, and underscore potential mechanisms driving depression's growing burden and how understanding these factors is critical for improving prevention and treatment strategies.
Humans ; Circadian Rhythm/physiology* ; Depressive Disorder, Major/therapy* ; Animals ; Sleep/physiology* ; Depression/therapy*

Depression is an affective disorder caused by multiple factors,and its pathogenesis is still unclear.However,in recent years,studies have found an association between neuroinflammation and depression,which is mainly reflected in the interaction of their pathogeneses,such as abnormalities of monoamine neurotransmitters in the brain,dysregulation of the hypothalamic-pituitary-adrenal axis,and dysfunction of neurogenesis.Currently,exercise as a therapy for depression has attracted widespread attention.By reviewing relevant research reports,this article summarizes that exercise alleviates neuroinflammation by playing an anti-inflammatory role,thus improving the mood-related pathway to treat depression.Furthermore,this article explores the effects of different exercise prescriptions on the anti-inflammatory role of exercise,aiming to provide new scientific ideas for the treatment of depression associated with neuroinflammation.
Humans ; Depression/therapy* ; Neuroinflammatory Diseases/therapy* ; Exercise ; Inflammation ; Exercise Therapy ; Animals