Inositol possesses antifibrotic activity and mitigates pulmonary fibrosis.

BACKGROUND: Myo-inositol (or inositol) and its derivatives not only function as important metabolites for multiple cellular processes but also act as co-factors and second messengers in signaling pathways. Although inositol supplementation has been widely studied in various clinical trials, little is known about its effect on idiopathic pulmonary fibrosis (IPF). Recent studies have demonstrated that IPF lung fibroblasts display arginine dependency due to loss of argininosuccinate synthase 1 (ASS1). However, the metabolic mechanisms underlying ASS1 deficiency and its functional consequence in fibrogenic processes are yet to be elucidated. METHODS: Metabolites extracted from primary lung fibroblasts with different ASS1 status were subjected to untargeted metabolomics analysis. An association of ASS1 deficiency with inositol and its signaling in lung fibroblasts was assessed using molecular biology assays. The therapeutic potential of inositol supplementation in fibroblast phenotypes and lung fibrosis was evaluated in cell-based studies and a bleomycin animal model, respectively. RESULTS: Our metabolomics studies showed that ASS1-deficient lung fibroblasts derived from IPF patients had significantly altered inositol phosphate metabolism. We observed that decreased inositol-4-monophosphate abundance and increased inositol abundance were associated with ASS1 expression in fibroblasts. Furthermore, genetic knockdown of ASS1 expression in primary normal lung fibroblasts led to the activation of inositol-mediated signalosomes, including EGFR and PKC signaling. Treatment with inositol significantly downregulated ASS1 deficiency-mediated signaling pathways and reduced cell invasiveness in IPF lung fibroblasts. Notably, inositol supplementation also mitigated bleomycin-induced fibrotic lesions and collagen deposition in mice. CONCLUSION: These findings taken together demonstrate a novel function of inositol in fibrometabolism and pulmonary fibrosis. Our study provides new evidence for the antifibrotic activity of this metabolite and suggests that inositol supplementation may be a promising therapeutic strategy for IPF.

Efficacy and Safety of Chaihu Jia Longgu Muli Decoction in the Treatment of Poststroke Depression: A Systematic Review and Meta-Analysis.

OBJECTIVE: Chaihu Jia Longgu Muli decoction (CLMD) is widely used in the treatment of poststroke depression (PSD) in China. Some evidences show that it has advantages, but there lacks reliable evidence. This study aims to systematically evaluate the efficacy and safety of CLMD in the treatment of PSD. METHODS: All randomized controlled trials (RCTs) of CLMD in the treatment of PSD were searched from the following databases: PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and Chinese Biomedical Literature Service System (CBM), from their inception to May 2021. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 13 RCTs involving 1665 patients were finally included in this study, among which 5 RCTs were oral CLMD alone versus antidepressants, and 8 RCTs were oral CLMD with antidepressants versus antidepressants. Meta-analysis results showed that oral administration of CLMD could improve Hamilton's Depression Scale (HAMD) and the Modified Edinburgh-Scandinavian Stroke Scale (MESSS) scores, improve the Barthel index, and have a low rate of adverse reactions, but there was no significant difference in the total effective rate (p=0.21 > 0.05) and the National Institute of Health Stroke Scale (NIHSS) score (p=0.47 > 0.05) between the antidepressants group and the oral administration of the CLMD group. Oral CLMD combined with antidepressants could improve the total effective rate, HAMD, and MESSS score, but there was no significant difference in Barthel index (p=0.06 > 0.05) and the adverse reaction rate (p=0.14 > 0.05) between the two groups. CONCLUSION: Current evidence suggests that oral CLMD alone or with antidepressants is more effective and safer in the treatment of PSD than oral antidepressants. Due to the limitation of the quality and quantity of the included studies, more high-quality studies are needed to confirm the above conclusion.

The efficacy of acupuncture and moxibustion for early and middle-stage osteonecrosis of the femeral head: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Osteonecrosis of the femeral head (ONFH) occurs predominantly in young- and middle-aged people, and the disability rate is high in the late stage of the disease and most patients have to undergo total hip replacement. Clinically, increasing attention is paid to intervening early and middle-stage ONFH so as to delay its progress. Acupuncture and moxibustion (AM) is a unique method for treating ONFH in China. This study aims to summarize the advantages of AM for the treatment of ONFH. METHODS: A comprehensive literature search was conducted on the database with languages of English and Chinese. The medical subject titles used are "Osteonecrosis of the femoral head" and "acupuncture and moxibustion." Related words in the title or abstract including but were not limited to "necrosis of the femoral head," "avascular necrosis of the femoral head," "ischemic necrosis of the femoral head," "caput femoris necrosis," "bone paralysis," "bone erosion," and "bone atrophy." RESULTS: Nine randomized controlled trials were identified in this meta-analysis that included 630 subjects. Meta-analysis showed that the trial group that treated with conventional therapy combined with AM had a higher effective rate (Z = 2.27 P = 0.02) and excellent and good rate (Z = 4.85 P < 0.00001) and Harris hip function score (HHS) (Z = 2.31 P = 0.02) and lower incidence of related adverse reactions during treatment (Z = 2.82 P = 0.005) compared with the control group that treated with conventional therapy alone. CONCLUSIONS: AM for early and middle-stage ONFH is an effective and relatively safe intervention, which can improve the effective rate and excellent and good rate and HHS, and reduce the adverse reaction rate. Clinically, early and middle-stage ONFH can be intervened by combining with AM while taking conventional therapy to improve the efficacy.

Efficacy and safety of Chinese herbal compound in the treatment of functional constipation: A protocol for systematic review and meta-analysis.

BACKGROUND: Functional constipation refers to constipation without organic lesions caused by dietary factors, mood depression, changes in life rules, and poor bowel habits. Clinically, constipation is mainly manifested by changes of stool texture, difficulty or lack of bowel movement, and dry stool. Sometimes, it can be accompanied by abdominal distension and abdominal discomfort. Chinese herbal compound is a prescription which is composed of 2 or more medicinal flavors and is designed for relatively certain diseases and syndromes. Clinical studies have shown that TCM compounds have a good therapeutic effect on functional constipation, but there is no evidence of evidence-based medicine. The purpose of this study is to systematically evaluate the efficacy and safety of TCM compounds in the treatment of functional constipation, and to provide evidence-based basis for the clinical application of TCM compounds in the treatment of constipation. METHODS: A systematic search was performed on English database (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese database (CNKI, Wanfang, Weipu (VIP), CBM), in addition to the manual retrieval of Baidu and Google academic for randomized controlled trials (RCTs) on the treatment of functional constipation with Chinese herbal compound. The retrieval time limit was from the establishment of the database to August 2020. Two researchers independently screened the literature, extracted the data and evaluated the quality of the included studies. A meta-analysis was performed using RevMan5.3 software. RESULTS: In this study, the efficacy and safety of TCM herbal compounds in the treatment of functional constipation were evaluated by the overall effective rate, recovery rate, colonic transmission function, and other indicators. CONCLUSIONS: This study will provide reliable evidence-based evidence for the clinical application of Chinese herbal compound in the treatment of functional constipation. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/D5ECF.

[Effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum GH and PG in chronic atrophic gastritis rats].

OBJECTIVE: To observe the effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum growth hormone (GH) and pepsinogen (PG) in chronic atrophic gastritis (CAG) rats, and to explore the potential mechanism of heat-sensitive moxibustion for CAG. METHODS: A total of 66 male SD rats were randomized into a blank group (12 rats) and a model establishment group (54 rats). No intervention was given in the blank group. Rats in the model establishment group were intervented with compound pathogeny method for 12 weeks to establish CAG model, which were further divided into a model group (11 rats), a vitacoenzyme group (11 rats) and a moxibustion group (22 rats). In the moxibustion group, suspending moxibustion was applied at "Zhongwan" (CV 12) for 40 min. After the intervention of moxibustion, 0.9% sodium chloride solution was given by gavage (2 mL·kg-1·d-1). According to the changes of tail temperature, rats in the moxibustion group were divided into a heat-sensitive moxibustion group (11 rats) and a non-heat-sensitive moxibustion group (8 rats). The vitacoenzyme group was given vitacoenzyme as the same dose by gavage. The intervention was adopted once a day for 28 days. Changes of body weight were observed among the groups. Expressions of serum GH, PGⅠand PGⅡwere detected by ELISA, and the ratio of PGⅠand PGⅡ (PGR) was calculated. The morphological changes of gastric mucosa were observed by macroscopy and light microscope. RESULTS: ①After modeling, the body weight of rats in the model establishment group was lower than the blank group (P<0.01). Compared with the model group, the body weight of rats in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group was increased after intervention (P<0.05), and there were no significant differences among the intervention groups (P>0.05). ②Under macroscopy and light microscope, gastric tissue of rats after modeling showed dark red and pale gastric mucosa, lower plica and mucosal congestion. The glands of lamina propria were atrophied or disappeared with sparse and disordered arrangement, in which, lymphoid follicles and inflammatory cells could be observed. After intervention, morphology of gastric mucosa was improved in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group. ③Compared with the blank group, the serum levels of GH, PGⅠ, PGⅡ and PGR were decreased in the model group (P<0.05, P<0.01). Compared with the model group, the serum levels of GH, PGⅠand PGⅡwere increased in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group (P<0.05, P<0.01), the levels of PGR were increased without statistical difference (P>0.05). Compared with the vitacoenzyme group and the non-heat-sensitive moxibustion group, the serum levels of GH and PGⅠwere increased in the heat-sensitive moxibustion group (P<0.05). CONCLUSION: Heat-sensitive moxibustion at "Zhongwan" (CV 12) can improve the morphology of gastric mucosa in chronic atrophic gastritis rats, its mechanism may be related to the up-regulation of serum GH and PGⅠ.

[Clinical observation on the distribution characteristics and rules of pressing sensitive acupoints in bronchial asthma patients].

OBJECTIVE: To compare the distribution characteristics of pressing sensitive acupoints on the body surface between bronchial asthma (BA) patients and healthy subjects, and to analyze the distribution rules of pressing sensitive acupoints in BA patients. METHODS: Seventy BA patients and 70 healthy subjects were selected in this study. The pressing sensitive acupoints were checked with finger pulp and marked on human nerve segment graph. The numbers of pressing sensitive acupoints were counted and the positional relationship between distribution of pressing sensitive acupoints and the position of meridians and nerve segment was observed. RESULTS: (1) The incidence rates of pressing sensitive acupoints in BA patients group and healthy subjects group were 91.4% (64/70) and 15.7% (11/70) respectively, and the BA patients group was higher than the healthy subjects group (P<0.01). (2) The top 3 meridians with pressing sensitive acupoints occuring in BA patients were bladder meridian of foot-taiyang, lung meridian of hand-taiyin and large intestine meridian of hand-yangming, and the most frequent pressing sensitive acupoints were Feishu（BL 13）, Xinshu（BL 15）, Chize（LU 5） and Jueyinshu (BL 14). (3) The pressing sensitive acupoints in BA patients were distributed mainly on C4, C6 and T1-T6 nerve segment. CONCLUSION: Pressing sensitive acupoints have a close correlation with physical condition, and there is a close relation between pressing sensitive acupoints distribution and corresponding meridians and nerve segments in BA patients.

[Distributive regularity of pressing sensitive acupoints in chronic non-atrophic gastritis patients].

OBJECTIVE: To compare the distribution regularity of the pressure-sensitive acupoints in patients with chronic non-atrophic gastritis (CNAG) and healthy subjects, so as to provide suitable acupoint combinations for clinical treatment. METHODS: A total of 120 volunteer subjects including 60 CNAG patients (29 men and 31 women, (40.7±10.3) years at the average age) and 60 healthy subjects (28 men and 32 women, and (40.8±10.2) years at the average age) were enrolled in the present study. The pressure-sensitive acupoints were checked by a fixed operator using his finger pulp along the body trunk and the four limbs and marked on a prepared human dermatome graph. The number of pressing sensitive acupoints were counted, and the relationship between the distribution of the detected sensitive acupoints and the position of meridians and nerve segments was analyzed. RESULTS: The incidence of pressure-sensitive acupoint in CNAG patients and healthy subjects were 86.7% and 15.0%, respectively. In 60 CNAG patients, the most frequently met sensitive acupoints were Xuehai (SP10), Zhongwan (CV13), and Zhongting (CV17) in sequence, mainly covering the Conception Vessel, Spleen Meridian of Foot-Taiyin (SP), and the Stomach Meridian of Foot-Yangming (ST). The sensitive acupoints presented a nerve-segmental distribution within T7-T10 and L3-L5. CONCLUSION: The pressure-sensitive acupoints present a nerve-segmental distribution and have a higher corresponding rate with some meridians related to the stomach, especially under diseased conditions.