The chapter Zhouyu in Guoyu says "Qi of the heaven and the earth moves without losing its order." With lucidity ascending and turbidity descending， Qi moves in a normal state， and Yin and Yang consolidate the foundation of the body. The mutual interference between lucidity and turbidity leads to the disorder of Qi movement， thus causing diseases. It is a pathological state of disorder between ascending and descending， as well as between entering and exiting， gradually evolving into a state of turbidity affecting lucidity and transforming into pathogen， which can be used to interpret and analyze the core of disease pathogenesis. The theory of lucidity and turbidity is connected with the harmony of nutrient and defensive aspects， Qi circulation， and sweat pore associating with Qi movement， and it has common implications with immune responses and nutrient metabolism system， intestinal mucosal barrier function， and mitochondrial energy synthesis. Modern studies have shown that intestinal flora imbalance， bile acid receptor inactivation， macrophage polarization imbalance， epithelial-mesenchymal transition， ferroptosis and other related microscopic pathological mechanisms are involved in the development and progression of ulcerative colitis. By delving into the common meaning of the classic theory of mutual interference between lucidity and turbidity in traditional Chinese medicine and modern medical pathological mechanisms， this paper summarizes the correspondence between the micropathological mechanism and the theory of mutual interference between lucidity and turbidity in the regulation and mamagement of ulcerative colitis. The combined use of sweet and warm medicinal materials consolidates the middle Qi and activates Qi circulation， thus ascending lucidity and descending turbidity. The combined use of pungent medicinal materials for dispersing and bitter medicinal materials for descending simultaneously raises warm and clear Qi. Wind-extinguishing medicinal materials facilitate the ascending of Qi and the opening of sweat pores. Accordingly， turbidity descends and lucidity ascends. The prescriptions incorporating these medication principles are in agreement with the therapeutic approach of following the normal flow of lucidity and turbidity. This paper clarifies the scientific connotation and micropathologic mechanism of ulcerative colitis from the perspective of mutual interference between lucidity and turbidity， providing new theories and prescriptions for the clinical diagnosis， treatment， and prevention of ulcerative colitis.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveA qualitative analysis method was established for the composition of Astragali Radix（AR） before and after rice stir-frying. On the basis of systematic characterization of the chemical compositions in AR and stir-fried AR with rice（ARR）， the structures of their major compounds were deduced and identified， and the differential compositions between them were analyzed. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the samples of AR and ARR in positive and negative ion modes， respectively. The compounds were analyzed and identified through self-constructed databases， literature， and reference standards， etc. And the data were analyzed by chemometrics， in order to screen for the differential components between AR and ARR. ResultsA total of 123 compounds were identified in AR and ARR， including 41 flavonoids， 19 terpenoids， 26 organic acids， 8 amino acids， 5 nucleotides， 5 carbohydrates and 19 other compounds. Among them， there were 95 common components in both， 18 unique components in AR， and 10 unique components in ARR. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） results both showed that there were significant differences in the chemical constituents of AR before and after rice stir-frying， and a total of 26 constituents with differences in the content were screened out， including L-canavanine， L-pyroglutamic acid， L-phenylalanine， cis-caffeic acid， and malonylastragaloside Ⅰ. Among them， 19 constituents of ARR were down-regulated and 7 constituents were up-regulated by comparing with AR. ConclusionThis study clarifies that the chemical composition of AR and ARR is mainly composed of flavonoids， terpenoids， and organic acids， and analyzes the components with significant differences in content between the two in combination with chemometrics， and the differential components are dominated by amino acids， organic acids and terpenoids， which can provide reference for the subsequent quality control and material basis research.

BACKGROUND:At present,there are few reports on the postoperative efficacy of arthroscopic coracoid tunnel-free suspension fixation and coracoid single tunnel fixation in the treatment of acromioclavicular joint dislocation at home and abroad.The specific clinical efficacy of the two procedures and whether there are other risks need to be explored. OBJECTIVE:To compare the short-term postoperative clinical efficacy of arthroscopic TightRope band plate fixation with single tunnel fixation of the coracoid process and tunnel-free suspension fixation of the coracoid process in the treatment of acute type Ⅲ-Ⅴ acromioclavicular joint dislocation. METHODS:A retrospective analysis was performed in 45 patients with acromioclavicular joint dislocation who met the inclusion criteria admitted to the Sixth Affiliated Hospital of Xinjiang Medical University from June 2019 to September 2022,and were divided into coracoid single tunnel fixation group(20 cases)and coracoid tunnel-free suspension fixation group(25 cases)according to the surgical treatment plan.Operation time,incision length,blood loss,Constant-Murley score,visual analogue scale score,the American Shoulder and Elbow Surgeons(ASES)score and intraoperative and postoperative complications of the shoulder joint before operation,3 months after surgery and the last follow-up were compared between the two groups. RESULTS AND CONCLUSION:All patients successfully completed the operation,and there was no important nerve or blood vessel damage during the operation.The operation time of the coracoid tunnel-free suspension fixation group was significantly shorter than that of the coracoid tunnel-free suspension fixation group(P<0.05).There was no significant difference in intraoperative blood loss and incision length between the two groups(P>0.05).All patients were followed up for 12 to 24 months,with an average of(15.29±2.73)months.In the coracoid single tunnel fixation group,at 3 months after operation and the final follow-up,the visual analogue scale score was significantly lower than the preoperative score(P<0.05);Constant-Murley score and ASES score were significantly increased compared with the preoperative values(P<0.05).In the coracoid tunnel-free suspension fixation group,at 3 months after operation and the final follow-up,the visual analogue scale score was significantly lower than the preoperative score(P<0.05);the Constant-Murley score and the ASES score were both significantly higher than the preoperative scores(P<0.05).At 3 months after operation,the Constant-Murley score of the coracoid tunnel-free suspension fixation group was higher than that of the coracoid single tunnel fixation group(P<0.05),while there was no significant difference in visual analogue scale and ASES scores between the two groups(P>0.05).There was also no significant difference in the visual analogue scale,Constant-Murley,and ASES scores between the two groups at the corresponding time points before surgery and at the final follow-up(P>0.05).Intraoperative and postoperative complications:In the coracoid single tunnel fixation group,there was one case of coracoid cortical rupture and fracture during the tunnel drilling during the operation,and one case of a loss of reduction at 3 months after operation,which was repositioned and fixed with hook plate transposition of the coracoacromial ligament.All patients had good acromioclavicular joint function recovery and no re-dislocation at the final follow-up.All patients in the coracoid tunnel-free suspension fixation group did not suffer from coracoid fractures,loss of reduction and other complications during surgery,postoperatively and at the last follow-up.To conclude,these two arthroscopic treatments for acute type Ⅲ-Ⅴ acromioclavicular joint dislocation have the advantages of less trauma,reliable reduction and fixation,and good recovery of shoulder joint function after operation.However,compared with the coracoid single tunnel technique,the coracoid tunnel-free suspension fixation requires shorter time,faster recovery of shoulder joint function in the short term,and avoids the establishment of bone tunnels on the coracoid process,which reduces the probability of iatrogenic fracture of the coracoid process during operation and provides a higher degree of safety.

BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.

Astragaloside Ⅳ （AS-Ⅳ） is a natural triterpenoid saponin compound derived from Astragalus membranaceus and has shown significant potential in the regulation of liver diseases. This article reviews the latest research advances in AS-Ⅳ in the field of liver diseases in China and globally， and it is found that AS-Ⅳ exerts a liver-protecting effect by regulating lipid metabolism， exerting an anti-tumor/anti-inflammatory/anti-fibrotic effect， and modulating gut microbiota. Its mechanism of action involves multiple signaling pathways， such as AMPK， NLRP3， NF-κB， JAK2/STAT3， and Nrf2. These research findings provide a scientific basis for the development of liver-protecting drugs or functional foods based on the natural product AS-Ⅳ.

Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*