OBJECTIVE To establish the ultra-high performance liquid chromatography （UPLC） fingerprint of Jingtian granule， and to evaluate its quality by chemical pattern recognition. METHODS Luna® Omega Polar C18 column （150 mm×2.1 mm， 1.6 μm） was used as the chromatographic column， and acetonitrile-0.2% phosphoric acid solution was used as the mobile phase for gradient elution. The flow rate was 0.2 mL/min， the column temperature was 30 ℃， and the detection wavelength was 265 nm. With peak 16 as the reference peak， the UPLC fingerprint of Jingtian granule was established by the Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）. The common peaks were identified， the similarity evaluation was carried out， and the ownership of each common peak was confirmed. Hierarchical cluster analysis （HCA） and principal component analysis （PCA） in chemical pattern recognition methods were used to classify 13 batches of samples （S1- S13）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） was used to identify the key components of the differences between different batches of samples. RESULTS RSDs of precision， repeatability and stability of the UPLC method were not more than 4.4%. A total of 25 common peaks were identified in the fingerprints of 13 batches of Jingtian granules. By comparing with the reference substance fingerprint， 10 common peaks were identified， namely peak 3 （hydroxymethyl-2-furaldehyde）， peak 5 （salidroside）， peak 8（chlorogenic acid）， peak 15 （cinnamic acid）， peak 19 （aloe-emodin）， peak 20 （ammonium glycyrrhizinate）， peak 21 （rhein）， peak 23 （emodin）， peak 24 （glycyrrhetinic acid）， peak 25 （chrysophanol）. The similarities of fingerprints of 13 batches of samples were 0.955-0.996. The results of HCA showed that 13 batches of samples could be divided into three categories， among which samples S1， S5， S7， S11-S13 were clustered in one category， S4 and S6 were clustered in one category， S2， S3 and S8-S10 were clustered in one category. PCA results showed that the cumulative variance contribution rate of principal components 1-7 was 92.666%. OPLS-DA further identified 13 differential components， which were mainly derived from Polygonati Rhizoma with wine steaming， Rhodiolae Crenulatae Radix Et Rhizoma， prepared Rhei Radix Et Rhizoma and Glycyrrhizae Radix Et Rhizome Praeparata Cum Melle. CONCLUSIONS The established UPLC fingerprint of Jingtian granule is simple， stable and reproducible. Combined with the chemical pattern recognition method， it can effectively reveal the overall quality difference between different batches of Jingtian granule. The quality of Polygonati Rhizoma with wine steaming， Rhodiolae Crenulatae Radix Et Rhizoma， prepared Rhei Radix Et Rhizoma， Dioscoreae Nipponicae Rhizoma， Polyporus， Cinnamomi Ramulus， Glycyrrhizae Radix Et Rhizome Praeparata Cum Melle is the key to the overall quality of Jingtian granule.

Objective To investigate the changes in the prevalence of Babesia microti infections, spleen morphology and proportions of splenic immune cells in BALB/c mice following intravenous and intraperitoneal injections, so as to provide insights into unraveling the immune regulatory mechanisms of Babesia infections. Methods Laboratory - maintained B. microti strains were prepared into whole blood samples with 10% prevalence of B. microti infection. A total of 75 BALB/c mice were randomly divided into three groups, including the normal control group, intravenous injection group, and intraperitoneal injection group, of 25 mice in each group. Mice in the intravenous and intraperitoneal injection groups were administered 100 μL of whole blood samples with 10% prevalence of B. microti infection, with the day of injection recorded as d0, and animals in the normal control group were given no treatments. Blood was sampled from mice in each group via the tail tip on d7, d14, d21, d28 and d35, and prepared into thin-film blood smears, and B. microti infection was observed in red blood cells. Five mice were randomly sampled from each group and sacrificed on d7, d14, d21, d28 and d35, and spleen was collected for measurement of spleen size and weight. In addition, splenic cells were isolated, and the proportions of CD3e⁺ T cells, CD45R⁺ B cells, CD49b⁺ nature killer (NK) cells, and F4/80⁺ macrophages were detected in CD45⁺ lymphocytes using flow cytometry. Results The prevalence of B. microti infection in the intravenous (22.80%) and intraperitoneal injection groups (44.82%) peaked on d7 (χ² = 8.141, P < 0.01) and then rapidly decreased, and no parasites were observed on d35. The longest mouse spleen length [(32.91 ± 2.20) mm] and width [(9.82 ± 0.43) mm], and the greatest weight [(0.78 ± 0.10) g] were found on d14 in the intravenous injection group, and the longest spleen length [(32.42 ± 3.21) mm] and width [(10.25 ± 0.73) mm], and the greatest weight [(0.73 ± 0.09) g] were seen in the intra-peritoneal injection group on d21, d7 and d14, respectively. There were significant differences among the intravenous injection group, intraperitoneal injection group and the normal control group in terms of spleen length (F = 10.310, P < 0.05), width (F = 9.824, P < 0.05), and weight (F = 10.672, P < 0.05) on d21, and the mouse spleen length, width and weight were all significantly greater in the intraperitoneal injection group than in the intravenous injection group (allP values < 0.05). The proportions of splenic CD3e⁺ T cells [(60.60 ± 6.20)% and (39.68 ± 7.62)%], CD45R⁺ B cells [(43.32 ± 2.08)% and (49.53 ± 4.90)%], CD49b⁺ NK cells [(6.88 ± 1.34)% and (7.71 ± 1.59)%], and F4/80⁺ macrophages [(2.21 ± 0.29)% and (3.80 ± 0.35)%] peaked on d14, d21, d21 and d14 in the intravenous and intraperitoneal injection groups, respectively. There were significant differences in the proportions of CD3e⁺ T cells (F = 16.730, P < 0.05) and F4/80⁺ macrophages (F = 15.941, P < 0.05) among the intravenous injection group, intraperitoneal injection group and normal control group on d14, and a higher proportion of CD3e⁺ T cells and a lower proportion of F4/80⁺ macrophages were detected in the intravenous injection group than in the intraperitoneal injection group (both P values < 0.01). There were significant differences among the intravenous injection group, intraperitoneal injection group and normal control group on d21 in terms of proportions of splenic CD3e⁺ T cells (F = 9.252, P < 0.05), CD45R⁺ B cells (F = 14.349, P < 0.05), CD49b⁺ NK cells (F = 13.436,P < 0.05), and F4/80⁺ macrophages (F = 8.180, P < 0.05), and a higher proportion of CD3e⁺ T cells and lower proportions of CD45R⁺ B cells and F4/80⁺ macrophages were detected in the intravenous injection group than in the intraperitoneal injection group (all P values < 0.01). In addition, there was a significant difference in the proportion of CD3e⁺ T cells among the intravenous injection group, intraperitoneal injection group and normal control group on d28 (F = 9.772,P < 0.05), and a lower proportion of CD3e⁺ T cells was found in the intravenous injection group than in the intraperitoneal injection group (P < 0.01). Conclusions Both intraperitoneal and intravenous routes are effective to induce B. microti infections in BALB/c mice, and the prevalence of B. microti infections is higher in BALB/c mice through the intraperitoneal route than through the intravenous route. Intraperitoneal and intravenous injections with B. microti cause diverse spleen morphologies and proportions of splenic immune cells in mice, indicating routes of B. microti infections cause different impacts on immune response mechanisms in mice.

This study aims to investigate the scientificity and efficacy of the compatibility of Jinlingzi San from pharmacokinetics. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was utilized to determine the plasma concentrations of the active components: toosendanin, tetrahydropalmatine A, and tetrahydropalmatine B at various time points following the gavage of Jinlingzi San and its single medicines in rats. Subsequently, WinNonlin was employed to calculate pertinent pharmacokinetic parameters. The pharmacokinetic parameters in rat plasma were compared between the single medicines and the compound formula of Jinlingzi San. It was discovered that the area under the curve(AUC_(all)) and peak concentrations(C_(max)) of tetrahydropalmatine A, and tetrahydropalmatine B were significantly elevated in the compound formula group compared with the single medicine groups. Conversely, the AUC_(all )and C_(max) of toosendanin notably decreased. Furthermore, the compound formula group had longer mean residence time(MRT) and lower apparent clearance(CL/F) of all three active ingredients than the single medicine groups(P<0.05). These findings indicated that Jinlingzi San enhanced the absorption of tetrahydropalmatine A and tetrahydropalmatine B in vivo, facilitating their pharmacological actions. Concurrently, it inhibited the absorption of toosendanin, thereby preventing potential toxic reactions. Moreover, the compatibility prolonged the residence time of the active ingredients in the body. This study provides a reference for exploring the compatibility rationality of Jinlingzi San.
Animals ; Rats ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Chromatography, Liquid/methods* ; Berberine Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry

Despite that sleep disturbance and poor neurocognitive performance are common complaints among coronavirus disease 2019 (COVID-19) survivors, few studies have focused on the effect of post-COVID-19 sleep disturbance (PCSD) on cognitive function. This study aimed to identify the impact of PCSD on neurocognitive function and explore the associated risk factors for the worsening of this condition. This cross-sectional study was conducted via the web-based assessment in Chinese mainland. Neurocognitive function was evaluated by the modified online Integrated Cognitive Assessment (ICA) and the Number Ordering Test (NOT). Propensity score matching (PSM) was utilized to match the confounding factors between individuals with and without PCSD. Univariate analyses were performed to evaluate the effect of PCSD on neurocognitive function. The risk factors associated with worsened neurocognitive performance in PCSD individuals were explored using binary logistic regression. A total of 8692 individuals with COVID-19 diagnosis were selected for this study. Nearly half (48.80%) of the COVID-19 survivors reported sleep disturbance. After matching by PSM, a total of 3977 pairs (7954 individuals in total) were obtained. Univariate analyses revealed that PCSD was related to worse ICA and NOT performance (P<0.05). Underlying disease, upper respiratory infection, loss of smell or taste, severe pneumonia, and self-reported cognitive complaints were associated with worsened neurocognitive performance among PCSD individuals (P<0.05). Furthermore, aging, ethnicity (minority), and lower education level were found to be independent risk factors for worsened neurocognitive performance in PCSD individuals (P<0.05). PCSD was related to impaired neurocognitive performance. Therefore, appropriate prevention and intervention measures should be taken to minimize or prevent PCSD and eliminate its potential adverse effect on neurocognitive function.
Humans ; COVID-19/epidemiology* ; Male ; Female ; Sleep Wake Disorders/epidemiology* ; Propensity Score ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Aged ; Risk Factors ; China/epidemiology* ; Cognition ; Cognitive Dysfunction/etiology* ; Neuropsychological Tests

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Chemotherapeutic drugs, such as cisplatin and phenanthriplatin (PhenPt), as STING agonists to induce DNA damage and activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway provides a potential strategy for clinical chemo-immunotherapy. However, treatment with Pt-based drugs leads to irreversible ectopia of phosphatidylserine (PS), a major component of the intracellular membrane, to the surface of the cancer cells by enzymes (Xkr8). Exposed PS can bind to immune cell receptors and inhibit the presentation of tumor antigens, leading to immunosuppression and attenuation of chemotherapy. Herein, we report a novel approach to enhance chemo-immunotherapy by constructing siRNA targeted Xkr8 (siXkr8)-mediated tetrahedral framework nucleic acid nanogel structure concurrently loaded with PhenPt (siXkr8-FNG/PhenPt) for co-delivery of siRNA and Pt-based drugs. The results showed that siXkr8-FNG/PhenPt can not only be used as an efficient delivery carrier to deliver siXkr8, block the expression of Xkr8, reduce the exposure of PS on the cancer cells surface, but also act as an immune stimulant to activate cGAS-STING pathway, effectively improve the immunosuppressive microenvironment, produce antitumor immune response, and inhibit tumor growth and metastasis. Overall, this new delivery system is important for improving the effect of Pt-based drug chemotherapy, inducing immune enhancement and nucleic acid drug delivery.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

OBJECTIVE: Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied. METHODS: A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels. RESULTS: Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein-protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds. CONCLUSION Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration. Please cite this article as: Zhang Y, Zhao XY, Liu MT, Zhou ZC, Cheng HB, Jiang XH, Zheng YR, Chen Z. Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia. J Integr Med. 2025; 23(2): 169-181.
Animals ; Nerve Regeneration/drug effects* ; Mice ; Peripheral Nerve Injuries/physiopathology* ; Male ; Ganglia, Spinal/enzymology* ; Axons/physiology* ; Peroxidase/antagonists & inhibitors* ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/pharmacology* ; Disease Models, Animal ; Strychnine/pharmacology*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*