Gut microbial metabolites in MASLD: Implications of mitochondrial dysfunction in the pathogenesis and treatment.

With an increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health problem. MASLD is well-known as a multifactorial disease. Mitochondrial dysfunction and alterations in the gut bacteria are 2 vital events in MASLD. Recent studies have highlighted the cross-talk between microbiota and mitochondria, and mitochondria are recognized as pivotal targets of the gut microbiota to modulate the host's physiological state. Mitochondrial dysfunction plays a vital role in MASLD and is associated with multiple pathological changes, including hepatocyte steatosis, oxidative stress, inflammation, and fibrosis. Metabolites are crucial mediators of the gut microbiota that influence extraintestinal organs. Additionally, regulation of the composition of gut bacteria may serve as a promising therapeutic strategy for MASLD. This study reviewed the potential roles of several common metabolites in MASLD, emphasizing their impact on mitochondrial function. Finally, we discuss the current treatments for MASLD, including probiotics, prebiotics, antibiotics, and fecal microbiota transplantation. These methods concentrate on restoring the gut microbiota to promote host health.

Association between gut microbiota and common overlapping gastrointestinal disorders: a bidirectional two-sample Mendelian randomization study.

Background: The main functional gastrointestinal disorders (FGIDs) include functional dyspepsia (FD) and irritable bowel syndrome (IBS), which often present overlapping symptoms with gastroesophageal reflux disease (GERD), posing a challenge for clinical diagnosis and treatment. The gut microbiota is closely associated with FGIDs and GERD, although the causal relationship has not been fully elucidated. Therefore, we aimed to investigate the potential causal relationship using bidirectional two-sample Mendelian randomization (MR) analysis. Materials and methods: The genetic data of the 211 gut microbiota were obtained from the MiBioGen consortium (N = 14,306, from phylum to genus level) and species level of gut microbiota were acquired from the Dutch Microbiome Project (N = 7,738). For FD and IBS, we utilized the FinnGen consortium, whereas, for GERD data analysis, we obtained the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was used as the primary method to calculate causal effect values. Sensitivity analyses were also performed to confirm the robustness of the primary findings of the MR analyses. Moreover, a reverse MR analysis was conducted to assess the likelihood of reverse causality. Results: Combining the results of the preliminary and sensitivity analyses, we identified that 8 gut microbial taxa were associated with FD. Genus Lachnospiraceae NK4A136 group (p = 3.63 × 10-3) and genus Terrisporobacter (p = 1.13 × 10-3) were strongly associated with FD. At the same time, we found that 8 gut microbial taxa were associated with IBS. Family Prevotellaceae (p = 2.44 × 10-3) and species Clostridium leptum (p = 7.68 × 10-3) display a robust correlation with IBS. In addition, 5 gut microbial taxa were associated with GERD using the IVW approach. In the reverse MR analysis, 2 gut microbial taxa were found to be associated with FD, 5 gut microbial taxa were found to be associated with IBS, and 21 gut microbial taxa were found to be associated with GERD. Conclusion: The study reveals the potential causal effects of specific microbial taxa on FD, IBS, and GERD and may offer novel insights into the diagnosis and treatment of these conditions.

Efficacy of electro-acupuncture versus sham acupuncture for diabetic peripheral neuropathy: study protocol for a three-armed randomised controlled trial.

INTRODUCTION: Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes. METHODS AND ANALYSIS: This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2200061408.

Effect of electroacupuncture at "Neiguan" (PC 6) and "Zusanli" (ST 36) on gastrointestinal hormone in the antral tissue of rats with functional dyspepsia. / 电针"å† å ³""足三里"å¯¹åŠŸèƒ½æ€§æ¶ˆåŒ–ä¸è‰¯å¤§é¼ èƒƒçª¦ç»„ç»‡èƒƒè‚ æ¿€ç´ çš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6) and "Zusanli"(ST 36) on the gastric emptying rate, the level of serotonin (5-HT) and the protein expression of motilin (MTL), ghrelin, substance P (SP) and vasoactive intestinal peptide (VIP) in the antral tissue of the rats with functional dyspepsia (FD) and explore the effect mechanism of EA in treatment of FD. METHODS: A total of 21 SPF male SD rat pups were randomly divided into a normal group, a model group and an EA group, with 7 rats in each group. In the model group and the EA group, FD model was prepared by the gavage with 0.1% sucrose iodoacetamide solution combined with the modified small platform method. After the successful modeling, EA was applied to "Neiguan" (PC 6) and "Zusanli"(ST 36) in the rats of the EA group, with disperse-dense wave, 20 Hz/100 Hz in frequency, stimulated for 30 min, once daily, for 7 days consecutively. Before and after intervention, the general condition of the rats was observed in each group. After the completion of intervention, the gastric emptying rate was measured, the morphological changes of gastric antral tissue were observed using HE staining, the level of 5-HT was detected with ELISA method, and the protein expression of MTL, ghrelin, SP, and VIP was determined with Western blot method in the antral tissue of rats. RESULTS: In the normal group, the rats were in a good mental state, with lustrous fur, flexible movement and the increase of food intake and body mass. In the model group, the rats were poor in mental state, lack of lustre in fur, preference for the body curled up, reduced activity and response; and a part of rats had loose stool, obviously enlarged gastric body and gastric food retention. In the EA group, the general condition of rats, e.g. the mental state, food intake and activity, were improved, the gastric body got smaller obviously and the gastric food retention was reduced when compared with the model group. The antral structure was intact, the glands were rich and no injury of the gastric mucosa was found, e.g. inflammatory reaction and edema in the rats of each group. Compared with the normal group, the gastric emptying rate was decreased (P<0.01), 5-HT level was increased (P<0.01), the protein expression of MTL and ghrelin was reduced (P<0.01) and that of VIP was elevated (P<0.01) in the rats of the model group. The gastric emptying rate was increased (P<0.01), 5-HT level was decreased (P<0.01), and the protein expression of MTL and ghrelin was elevated (P<0.05, P<0.01) in the rats of the EA group when compared with those in the model group. CONCLUSIONS: Electroacupuncture at "Neiguan" (PC 6) and "Zusanli"(ST 36) may effectively relieve gastric dysfunction, strengthen gastric motility and promote gastric emptying so as to alleviate the symptoms of dyspepsia in FD rats, and its mechanism may be related to the regulation of gastrointestinal hormones in the antral tissue.

[An anti-scald device for warm needling].

Warm needling, i.e. acupuncture with the needle warmed by burning moxa stick or cone, is frequently employed in the treatment of cold and dampness type disorders. During treatment, accidental skin scald may occur if the burning moxa drops on the skin due to slight changes in patient's body position. Thus, we designed and developed an anti-scald device for warm needling which is suitable for any part of the body. This device is made up of two parts, a stainless steel-grid moxa cartridge (including half cylinder, hinge shaft, lug, limit bar, clamping arm, connecting arm, torsion spring, heat insulation pad, through holes) and a clamp holder which is in an integrated structure. The grid moxa cartridge can be used to wrap the burning mugwort cone in all directions to prevent the ignited moxa-cone from falling and skin scalding, and effectively collect the burned moxa ash. At the same time, the clamp holder can be used to help fix the moxa-cone to increase the stability of warm needling operation. The device is convenient to operate and novel in design, can effectively reduce the occurrence of scald accidents in clinical treatment, save time and manpower, and has both economic and ecological benefits, being helpful to the promotion and use of warm needling.

[Influence of Herbal-cake-separated Moxibustion on Contents of 5-HT, DA and NE in Hypothalamus in Rats with Functional Dyspepsia of Liver Stagnation and Spleen Deficiency Syndrome].

OBJECTIVE: To observe the influence of herbal cake-separated moxibustion on the contents of 5-hydroxy tryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the hypothalamus in rats with functional dyspepsia (FD) of syndrome of liver stagnation and spleen deficiency, so as to explore its mechanism underlying improvement of FD. METHODS: Sixty SD rats were randomly divided into 6 groups: control, model, herbal cake-separated moxibustion, moxa-cone moxibustion, Xiaoyaosan (decoction for relieving liver stagnation) and Domperidon, with 10 rats in each group. The FD model was established by applying chronic restraint stress + excessive fatigue + irregular food + tail clipping+ shaking for 21 consecutive days. Moxibustion (herbal cake-separated or moxa-cone) was applied to bilateral "Ganshu" (BL 18), "Pishu" (BL 20) and "Weishu" (BL 21), or "Zhangmen"(LR 13), "Qimen" (LR 14) and "Zhongwan" (CV 12) for 30 min, once daily for 14 d. For rats of the two medication groups, Xiaoyaosan [1 mL (2 g)/100 g] and Domperidone [1 mL (0.3 g)/100 g] were administrated by gavage, respectively. The contents of 5-HT, DA and NE in the hypothalamus tissue were detected by high performance liquid Phrnm.tnrnh, RESULTS: The gastric empty rate was obviously lower in the model group than in the control group (P<0. 01). After the treatment, the gastric empty rate in the herbal cake-separated moxibustion, moxa-cone moxibustion, Xiaoyaosan and Domperidone groups were significantly increased in comparison with the model group ( P<0. 01) , but there were no significant differences among the four treatment groups (P > 0.05). Compared to the control group, the contents of 5-HT, DA and NE in the hypothalamus were markedly decreased in the model group (P < 0.01), while compared to the model group, the contents of hypothalamic 5- HT, DA and NE contents were significantly up-regulated in both the herbal cake-separated moxibustion and Xiaoyaosan groups (P < 0.01), rather than in the moxa-cone moxibustion and Domperidone groups (P > 0.05). No significant differences were found between the herbal cake-separated moxibustion and Xioayaosan groups in increasing hypothalamic 5-HT, DA and NE levels (P > 0.05). CONCLUSION: Herbal cake-separated moxibustion can promote the gastric empty rate in FD rats, which may be associated with its effects in inhibiting stress induced decrease of hypothalamic 5-HT, DA and NE levels.

[Post-stroke constipation treated with acupuncture therapy of regulating qi circulation of fu-organ].

OBJECTIVE: To compare the difference in the efficacy on post-stroke constipation between acupuncture therapy of regulating qi circulation of fe-organ and Shengxue Tongbian Capsules. METHODS: Seventy-five patients of post-stroke constipation were randomized into an acupuncture group (39 cases) and a Chinese medicine group (36 cases). The unit mode comprehensive therapy of stroke was adopted as basic treatment in the two groups. In the acupuncture group, acupuncture therapy of regulating qi circulation of fu-organ was added at Tianshu (ST 25), Zhigou (TE 6), Qihai (CV 6) and Zusanli (ST 36), once every day. In the Chinese medicine group, Shengrue Tongbian Capsules were supplemented for oral administration, once every day, 10 g each time. The clinical symptom score of constipation was observed before treatment, after 1 and 2 weeks treatment in the two groups, respectively. The efficacy in 1 week and 2 weeks of treatment and the adverse reaction were observed. RESULTS: In 1 and 2 weeks of treatment, the clinical symptom score of constipation was reduced significantly as compared with that before treatment in the two groups (all P < 0.05). The improvements in the acupuncture group were significant than those in the Chinese medicine group in 2 weeks of treatment (8.03 +/- 2.38 vs 9.20 +/- 2.45, P < 0.05). Concerning to the occurrence of adverse reaction, there was 1 case of local bruises in needling local site in the acupuncture group; and there were 1 case of abdominal pain, 3 cases of diarrhea and 2 cases of nausea and vomiting in the Chinese medicine group. CONCLUSION: Both the acupuncture therapy of regulating qi circulation of fu-organ and Shengxue Tongbian Capsules achieve the significant efficacy on post-stroke constipation. The efficacy of the acupuncture therapy of regulating qi circulation of fe-organ is better and the adverse reaction is less after long-term persistent treatment.

[Clinical observation on Tongdu Tiaojin needling method for treatment of blepharoptosis].

OBJECTIVE: To compare therapeutic effects of Tongdu Tiaojin needling method and routine acupuncture method on blepharoptosis. METHODS: Fifty-eight cases of blepharoptosis were randomly divided into an observation group and a control group, 29 cases in each group. The observation group was treated by Tongdu Tiaojin needling method with Baihui (GV 20), Fengchi (GB 20), Houxi (SI 3), Yintang (EX-HN 3) selected, and the control group by routine acupuncture method with Cuanzhu (BL 2), Yangbai (GB 14), Sizhukong (TE 23) selected. They were treated for 3 courses and one course was constituted by 10 sessions. RESULTS: The cured rate of 41.4% and the effective rate of 82.8% in the observation group were better than 24.1% and 48.2% in the control group (P<0.05); after treatment, the palpebral fissure widened and the level of the palpebra superior shading the cornea was alleviated in the two groups, but the observation group was superior to the control group (P<0.05). CONCLUSION: Tongdu Tiaojin needling method has a definite therapeutic effect on blepharoptosis.

[Treatment of 120 cases of pseudobulbar palsy of wind-phlegm type with needling method for dispelling wind and expelling phlegm].

OBJECTIVE: To observe clinical therapeutic effects of needling method for dispelling wind and expelling phlegm on pseudobulbar palsy of wind-phlegm type. METHODS: Two hundred and forty cases of pseudobulbar palsy of wind-phlegm type were randomly divided into an observation group and a control group, 120 cases in each group, and they were treated by needling method for dispelling wind and expelling phlegm, and intravenous dripping of cytidine diphosphate choline injection plus blank needling method, respectively. One month later, main symptoms and signs were systematically compared and assessed. RESULTS: The cured rate and the total effective rate were 40.7% and 89.0% in the observation group respectively, which were superior to 7.6% and 37.0% in the control group (P < 0.01). CONCLUSION: The needling method for dispelling wind and expelling phlegm has obvious therapeutic effect on pseudobulbar palsy of wind-phlegm type.