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.

BACKGROUND: The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards. RESULTS: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P  <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P  = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P  <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P  = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P  <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P  = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction. CONCLUSIONS In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Randomized Controlled Trials as Topic ; Treatment Outcome

This study aims to explore the role and mechanism of CXC chemokine receptor 3 (CXCR3) in cisplatin-induced skeletal muscle atrophy. Wild-type mice were divided into two groups: cisplatin group and control group (treated by normal saline). The results showed that, compared to the control group, the expression levels of CXCR3 mRNA and protein were significantly up-regulated in the skeletal muscle of the cisplatin group, suggesting that CXCR3 may play an important role in the model of cisplatin-induced skeletal muscle atrophy. To further investigate its role and potential mechanisms, CXCR3 knockout mice and wild-type mice were treated with cisplatin to induce skeletal muscle atrophy. The results revealed that CXCR3 knockout not only failed to alleviate cisplatin-induced skeletal muscle atrophy, but also further reduced body weight, skeletal muscle mass, and muscle fiber cross-sectional area. Further analysis showed that, in the cisplatin-induced muscle atrophy model, CXCR3 knockout significantly up-regulated the expression levels of E3 ubiquitin ligases in skeletal muscle and down-regulated the expression levels of myogenic regulatory factors. To explore the molecular mechanism by which CXCR3 gene deletion exacerbated cisplatin-induced skeletal muscle atrophy, transcriptomic sequencing was performed on the atrophied skeletal muscles of wild-type and CXCR3 knockout mice. The results showed that, compared to wild-type mice, 14 genes were significantly up-regulated and 12 genes were significantly down-regulated in the skeletal muscle of CXCR3 knockout mice. Gene set enrichment analysis (GSEA) revealed a significant enrichment of genes related to fatty acid β-oxidation. Quantitative real-time PCR validation results were consistent with the transcriptomic sequencing results. These findings suggest that CXCR3 may counteract cisplatin-induced skeletal muscle atrophy by up-regulating E3 ubiquitin ligases, down-regulating myogenic regulatory factors, and enhancing the recruitment of fatty acid β-oxidation-related genes.
Animals ; Cisplatin/adverse effects* ; Muscular Atrophy/physiopathology* ; Mice ; Receptors, CXCR3/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; Mice, Knockout ; Oxidation-Reduction ; Fatty Acids/metabolism* ; Muscle, Skeletal/metabolism* ; Mice, Inbred C57BL ; Male

Parkinson's disease (PD) is a common neurodegenerative disorder mainly related to mitochondrial dysfunction of dopaminergic neurons in the midbrain substantia nigra. This study aimed to investigate the effects of exercise preconditioning on motor deficits and mitochondrial function in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Eight-week-old male C57BL/6J mice were randomly divided into four groups: sedentary + saline (SS), sedentary + MPTP (SM), exercise + saline (ES), and exercise + MPTP (EM) groups. Mice in the ES and EM groups received 4 weeks of treadmill training, and then SM and EM groups were treated with MPTP for 5 days. Motor function was assessed by behavioral tests, and morphological and functional changes in dopaminergic neurons and mitochondria in the substantia nigra of the midbrain were evaluated using immunohistochemistry, Western blot, and transmission electron microscopy technology. The results showed that, compared with the SM group, the EM group exhibited significantly improved motor ability, up-regulated protein expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the midbrain, and down-regulated protein expression of α-synuclein (α-Syn) in the mitochondria of substantia nigra. Compared with the SM group, the EM group showed up-regulated protein expression levels of mitochondrial fusion proteins, including optical atrophy protein 1 (OPA1) and mitofusin 2 (MFN2), and biogenesis-related proteins, including peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM), while the protein expression levels of dynamin-related protein 1 (DRP1) and mitochondrial fission protein 1 (FIS1) were significantly down-regulated. Compared with the SM group, the EM group showed significantly reduced damage to substantia nigra mitochondria, restored mitochondrial membrane potential and ATP production, and decreased levels of reactive oxygen species (ROS). These results suggest that 4-week treadmill pre-training can alleviate MPTP-induced motor impairments in PD mice by improving mitochondrial function, providing a theoretical basis for early exercise-based prevention of PD.
Animals ; Male ; Physical Conditioning, Animal/physiology* ; Mice ; Mice, Inbred C57BL ; Mitochondria/physiology* ; Dopaminergic Neurons ; MPTP Poisoning/physiopathology* ; Substantia Nigra ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Abelmoschi Corolla, the dried corolla of Abelmoschus manihot, has anti-inflammatory, antioxidant, and anti-fibrosis activities. Its chemical constituents mainly include flavonoids, organic acids, steroids, and polysaccharides. This study reviewed the research progress in the chemical constituents and pharmacological activities of Abelmoschi Corolla in recent 20 years. According to the concept of quality marker(Q-marker), the Q-markers of Abelmoschi Corolla were predicted from plant phylogeny, chemical constituent specificity, traditional efficacy, chemical constituent measurability, and absorbed constituents. The primary Q-markers for Abelmoschi Corolla were anticipated to include quercetin-3'-O-β-D-glucopyranoside, gossypetin-8-O-β-D-glucuronide, isoquercetin, myricetin,quercetin, and hyperoside, with the aim of providing reference data for improving the quality evaluation system of Abelmoschi Corolla.
Abelmoschus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Flowers/chemistry* ; Humans ; Animals ; Quality Control ; Flavonoids/chemistry*

Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires