ObjectiveBased on the theory of "gut-prostate" axis， this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis（CNP） by detecting the levels of inflammatory factors， and the composition and structure of intestinal flora in CNP rats. MethodsEight out of 42 SD rats were randomly selected as the normal group， and the remaining rats were injected with carrageenan to prepare the CNP model. After successful modeling， 32 rats were randomly divided into the model group， Ningmitai capsule group（0.50 g·kg^-1）， Zishen Tongguan formula group（2.00 g·kg^-1）， and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group（PCC-AR group， 2.00 g·kg^-1）， with 8 rats in each group. The administered groups were given the corresponding medicinal solution by gavage， and the normal and model groups were intragastrically administered with an equal volume of normal saline， once a day for 14 consecutive days. The prostate tissues of rats were collected and subjected to hematoxylin-eosin（HE） staining and Masson staining to observe the pathological changes of the tissues in each group. Enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of related inflammatory factors in rat serum， and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration， and species difference analysis was performed. ResultsAll the administered groups could alleviate the inflammatory symptoms of CNP rats， increase the expression levels of anti-inflammatory factors and decrease the expression levels of pro-inflammatory factors， with the most sIgnificant effect observed in the Zishen Tongguan formula group. Compared with the normal group， the expression levels of interleukin（IL）-8， hypersensitive C-reactive protein（hs-CRP）， immunoglobulin（Ig）M， secretory IgA （sIgA）， and inducible nitric oxide synthase（iNOS） were sIgnificantly increased in the model group（P<0.01）. Compared with the model group， the expression levels of the above inflammatory factors in all administered groups were significantly reduced（P<0.01）. When compared with the PCC-AR group， the Zishen Tongguan formula group showed a significant decrease in transforming growth factor（TGF）-β₁ expression level（P<0.05） and a significant increase in IgM expression level（P<0.01）. The results of gut microbiota analysis showed that， compared with the PCC-AR group， at the order level， the Zishen Tongguan formula group significantly reduced the relative abundance of conditional pathogens such as Bacteroidales， Acidaminococcales， Rhodospirillales， Clostridiales， and Elusimicrobiales（P<0.01）. And at the genus level， the Zishen Tongguan formula group significantly decreased the relative abundance of pathogenic microbiota such as Lachnospira and Bacteroides（P<0.01） and significantly increased the relative abundances of beneficial microbiota such as Ruminococcus and Lactobacillus（P<0.01）. ConclusionZishen Tongguan formula can reduce the level of harmful intestinal bacteria， increase the level of beneficial intestinal bacteria， down-regulate the expression of serum inflammatory factors， and the small amount of Cinnamomi Cortex in the formula may play a key role in the treatment of CNP with this formula.

ObjectiveBased on the theory of "gut-prostate" axis， this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis（CNP） by detecting the levels of inflammatory factors， and the composition and structure of intestinal flora in CNP rats. MethodsEight out of 42 SD rats were randomly selected as the normal group， and the remaining rats were injected with carrageenan to prepare the CNP model. After successful modeling， 32 rats were randomly divided into the model group， Ningmitai capsule group（0.50 g·kg^-1）， Zishen Tongguan formula group（2.00 g·kg^-1）， and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group（PCC-AR group， 2.00 g·kg^-1）， with 8 rats in each group. The administered groups were given the corresponding medicinal solution by gavage， and the normal and model groups were intragastrically administered with an equal volume of normal saline， once a day for 14 consecutive days. The prostate tissues of rats were collected and subjected to hematoxylin-eosin（HE） staining and Masson staining to observe the pathological changes of the tissues in each group. Enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of related inflammatory factors in rat serum， and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration， and species difference analysis was performed. ResultsAll the administered groups could alleviate the inflammatory symptoms of CNP rats， increase the expression levels of anti-inflammatory factors and decrease the expression levels of pro-inflammatory factors， with the most sIgnificant effect observed in the Zishen Tongguan formula group. Compared with the normal group， the expression levels of interleukin（IL）-8， hypersensitive C-reactive protein（hs-CRP）， immunoglobulin（Ig）M， secretory IgA （sIgA）， and inducible nitric oxide synthase（iNOS） were sIgnificantly increased in the model group（P<0.01）. Compared with the model group， the expression levels of the above inflammatory factors in all administered groups were significantly reduced（P<0.01）. When compared with the PCC-AR group， the Zishen Tongguan formula group showed a significant decrease in transforming growth factor（TGF）-β₁ expression level（P<0.05） and a significant increase in IgM expression level（P<0.01）. The results of gut microbiota analysis showed that， compared with the PCC-AR group， at the order level， the Zishen Tongguan formula group significantly reduced the relative abundance of conditional pathogens such as Bacteroidales， Acidaminococcales， Rhodospirillales， Clostridiales， and Elusimicrobiales（P<0.01）. And at the genus level， the Zishen Tongguan formula group significantly decreased the relative abundance of pathogenic microbiota such as Lachnospira and Bacteroides（P<0.01） and significantly increased the relative abundances of beneficial microbiota such as Ruminococcus and Lactobacillus（P<0.01）. ConclusionZishen Tongguan formula can reduce the level of harmful intestinal bacteria， increase the level of beneficial intestinal bacteria， down-regulate the expression of serum inflammatory factors， and the small amount of Cinnamomi Cortex in the formula may play a key role in the treatment of CNP with this formula.

Anemia of chronic disease (ACD) is the most frequent clinical issue in patients with chronic disease. ACD is usually secondary to chronic kidney disease (CKD), cancer, and chronic infection, which is associated with poor health outcomes, increased morbidity and mortality, and substantial economic costs. Current treatment options for ACD are very limited. The discovery of the hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) pathway made it possible to develop novel therapeutic agents (such as hypoxia-inducible factor-prolyl hydroxylase inhibitor, HIF-PHI) to treat ACD by stabilizing HIF and subsequently promoting endogenous erythropoietin (EPO) production and iron absorption and utilization. Thus, HIF-PHIs appear to open a new door for the treatment of ACD patients with a novel mechanism. Here, we comprehensively reviewed the latest advancements in the application of HIF-PHIs in ACD. Specifically, we highlighted the key features of HIF-PHIs on ACD, such as stimulation of endogenous EPO, handling iron metabolism, inflammation-independent, and prolonging lifespan of red blood cells. In conclusion, the success of HIF-PHIs in the treatment of ACD may expand the therapeutic opportunity for other types of anemia beyond renal anemia.
Humans ; Anemia/metabolism* ; Chronic Disease ; Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism* ; Erythropoietin/metabolism* ; Prolyl-Hydroxylase Inhibitors/therapeutic use* ; Animals ; Renal Insufficiency, Chronic

OBJECTIVE To analyze the quantity transfer rule in the processing of Astragalus membranaceus before and after moistening-soaking and steaming-soaking followed by cutting. METHODS Three batches of A. membranaceus decoction pieces processed through moistening-soaking and steaming-soaking followed by cutting were prepared. The HPLC overlapping fingerprints of A. membranaceus and its decoction pieces were established through the Similarity Evaluation System of Chromatographic Fingerprints of TCM （2012 edition）. Combined with the previous qualitative analysis results， the common peaks were identified， the changes of common peak area were analyzed， and the principal component analysis was carried out. The contents of calycosin-7-glucoside， astragaloside Ⅰ and astragaloside Ⅳ in A. membranaceus and its decoction pieces were determined by HPLC， and the content differences of each component in different samples were compared. RESULTS The results of fingerprint analysis showed that 17 common peaks were identified. After steaming-soaking and moistening-soaking of A. membranaceus， the proportion of common peak area in the decoction pieces changed compared with the original medicine （for example， in A. membranaceus steaming-soaking decoction pieces， the proportion of peak area of malonyl calycosin-7-glucoside and malonyl astragaloside Ⅰ decreased， while the proportion of peak area of calycosin-7-glucoside increased）. The results of principal component analysis showed that A. membranaceus， and its decoction pieces after moistening-soaking and steaming-soaking followed by cutting were all clustered into one category respectively. The results of content determination showed that， compared with A. membranaceus， the average content of calycosin-7-glucoside in A. membranaceus moistening-soaking decoction pieces was significantly reduced （P＜0.05）； the average contents of calycosin-7-glucoside and astragaloside Ⅳ in A. membranaceus steaming- soaking decoction pieces were significantly increased （P＜0.05）； there was no significant difference in the average content of astragaloside Ⅳ in A. membranaceus moistening-soaking decoction pieces and astragaloside Ⅰ in the two decoction pieces （P＞ 0.05）. CONCLUSIONS There are differences in the quantity transfer rules of A. membranaceus before and after moistening-soaking and steaming-soaking followed by cutting. Steaming-soaking followed by cutting may make the transformation of unstable components （such as malonyl calycosin-7-glucoside and malonyl astragaloside Ⅰ） more complete.

Qualitative and quantitative analysis methods for chemical components of different processed products of Corni Fructus were established to systematically characterize and identify these components, and the content of the main differential components was determined. The chemical components of different processed products of Corni Fructus were collected using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Through analysis of self-built databases, literature, and reference standards, a total of 93 components were obtained, including 19 iridoids, 15 flavonoids, 16 organic acids, eight triterpenoids, eight tannins, four amino acids, two polysaccharides, five olefins, and 16 other compounds. Additionally, by using multivariate statistical methods, the differential components between different processed products of Corni Fructus were screened under the conditions of VIP>1.0 and FC<0.5 or FC>2.0 and P<0.05. The PCA and OPLS-DA results showed differences in the chemical components between different processed products of Corni Fructus. A total of 21 differential components were screened, including tartaric acid, morroniside, and rutin. On this basis, ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS) was used to determine the content of 10 main common differential components, including gallic acid, morroniside, ursolic acid, loganin, swertiamarin, rutin, 5-hydroxymethylfurfural, cornuside Ⅰ, quercetin, and oleanolic acid. The above 10 components showed a good linear relationship within the determined concentration range, with the precision, stability, repeatability, and sample recovery rate all meeting the requirements. Compared with that in Corni Fructus, the content of iridoid glycosides in wine-prepared Corni Fructus and wine-and honey-prepared Corni Fructus decreased, while the content of gallic acid, rutin, quercetin, 5-hydroxymethylfurfural, ursolic acid, and oleanolic acid increased. Compared with wine-prepared Corni Fructus, wine-and honey-prepared Corni Fructus showed varying degrees of increase in all other components, except for a slight decrease in gallic acid content. In summary, this study clarified the influence of different processing methods on the chemical components of Corni Fructus, providing a theoretical basis for the scientific connotation, overall quality evaluation, and clinically rational application of Corni Fructus processing in the future.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Cornus/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Fruit/chemistry*

Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

Ureaplasma urealyticum (UU) is one of the most commonly occurring pathogens associated with genital tract infections in infertile males, but the impact of seminal UU infection in semen on intrauterine insemination (IUI) outcomes is poorly understood. We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC (Hefei, China) between January 2021 and January 2023. The subjects were classified into two groups according to their UU infection status: the UU-positive group and the UU-negative group. We compared semen parameters, pregnancy outcomes, and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes. There were no significantly statistical differences in various semen parameters, including semen volume, sperm concentration, total and progressive motility, sperm morphology, leukocyte count, the presence of anti-sperm antibody, and sperm DNA fragmentation index (DFI), between the UU-positive and UU-negative groups of male infertile patients (all P > 0.05). However, the high DNA stainability (HDS) status of sperm differed between the UU-positive and UU-negative groups, suggesting that seminal UU infection may affect sperm nuclear maturation ( P = 0.04). Additionally, there were no significant differences in pregnancy or neonatal birth outcomes between the two groups (all P > 0.05). These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.
Humans ; Male ; Ureaplasma Infections/complications* ; Female ; Infertility, Male/therapy* ; Ureaplasma urealyticum/isolation & purification* ; Pregnancy ; Adult ; Pregnancy Outcome ; Semen Analysis ; Insemination, Artificial ; Semen/microbiology* ; China