ObjectiveTo observe the clinical efficacy and safety of Yuyin Lidan granules （YYLD） in preventing the recurrence of common bile duct stones （CBDS） in patients with liver and gallbladder dampness-heat syndrome following endoscopic retrograde cholangiopancreatography （ERCP）. MethodsThis randomized， parallel， controlled trial enrolled postoperative CBDS-ERCP patients who met the inclusion and exclusion criteria. Sixty-four patients were randomly assigned to an observation group or a control group， with 32 cases in each. Both groups received conventional Western medical treatment after ERCP， while the observation group additionally received YYLD for 8 weeks. The follow-up period lasted for 1 year. The efficacy indicators included bile bilirubin levels， traditional Chinese medicine （TCM） syndrome scores， clinical efficacy rate， pancreatitis and inflammation markers， postoperative liver function， and CBDS recurrence rate at 1-year follow-up， which were used to jointly evaluate the clinical efficacy and safety of both groups. ResultsA total of 56 patients completed the study and were included in the final analysis， i.e.， 29 in the observation group and 27 in the control group. Baseline characteristics were comparable between the two groups. Compared with pre-treatment and with the control group after treatment， the bile bilirubin level in the observation group significantly decreased （P<0.05）. After treatment， the clinical cure and marked improvement rates were higher in the observation group than in the control group， showing a statistically significant difference in overall clinical efficacy （P<0.05）. Compared with pre-treatment， the primary and secondary symptoms in the observation group， as well as the primary symptom and the secondary symptom of nausea and vomiting in the control group （weeks 4 and 8）， were significantly reduced （P<0.05）. Compared with the control group after treatment， the observation group showed significant reductions in the primary symptom of loose stools/constipation （day 5 and week 4） and in three secondary symptoms， i.e.， bitter taste and sticky dry mouth， abdominal distension and poor appetite （throughout the treatment period）， and general heaviness and fatigue （day 5 and week 4）， with statistical differences （P<0.05）. Compared with pre-treatment， both groups showed decreased lipase and urinary amylase levels （P<0.05）. However， no significant between-group differences were observed in pancreatitis or inflammation-related indices after treatment. Compared with pre-treatment， all liver function indicators in the observation group and alanine aminotransferase （ ALT ）， γ-glutamyl transferase （ γ-GT ）， alkaline phosphatase （ALP）， and conjugated bilirubin in the control group significantly decreased at weeks 4 and 8 （P<0.05）. Compared with the control group after treatment， only serum total bilirubin and unconjugated bilirubin were significantly reduced in the observation group during the treatment period （P<0.05）. ConclusionYYLD combined with conventional Western medical treatment can effectively regulate bilirubin metabolism （in bile and serum）， improve TCM clinical symptoms， and prevent CBDS recurrence after ERCP in patients with liver and gallbladder dampness-heat syndrome. This regimen is safe and effective and is worthy of further clinical research and promotion.

This study aimed to investigate the therapeutic effect of Yindan Pinggan capsules (YDPG) on intrahepatic cholestasis (IHC) through animal experiments, while utilizing network pharmacology and molecular docking techniques to explore its potential mechanisms. Initially, the therapeutic effect of YDPG on an α-naphthylisothiocyanate (ANIT)-induced IHC mouse model was assessed through liver function tests, routine blood tests, and liver pathology analysis. Subsequently, network pharmacology tools were employed to predict the active components, core targets, and signaling pathways of YDPG. Molecular docking technology was employed to verify the binding activity of key active components of YDPG with core targets, followed by protein immunoblotting to validate the key targets. Results showed that YDPG significantly improved liver function abnormalities and hepatocyte damage in IHC mice. Network pharmacology analysis revealed that 94 active components in YDPG were associated with 396 targets for the treatment of IHC, and were significantly enriched in pathways such as the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, lipid metabolism, and bile secretion. Molecular docking results showed good binding activity between key active components of YDPG and core targets of the PI3K-AKT signaling pathway. Further protein immunoblotting confirmed that YDPG could reduce the phosphorylation levels of PI3K and AKT proteins, core targets of the PI3K-AKT pathway in liver tissue. These findings suggest that YDPG may alleviate biological processes such as oxidative stress and inflammatory responses by regulating the PI3K-AKT signaling pathway, thereby improving liver damage in IHC mice and exerting a therapeutic effect on IHC. This experiment has been approved by the Animal Experiment Ethics Committee of Jinan University (ethical approval number: IACUC-20241011-09).

ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong （BL 40）" on neuropathic pain in a rat model of chronic constriction injury （CCI） of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups （8 rats in each group）， sham-operated group， model group， Tuina group， and blockade group. The CCI model was established in the model group， Tuina group， and the blockade group by ligating the sciatic nerve with catgut， while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14， rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong （BL 40）" using a dynamic pressure distribution measurement system （5 N pressure， 2 Hz frequency， 10 min per session， once daily）. The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline （10 mg/kg） once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold （MWT） and paw withdrawal latency （PWL） were measured before surgery and on day 3， 7， 10， and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair， measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 （Iba-1）， CD206， CD68， interleukin-10 （IL-10）， and β-endorphin （β-EP） precursor pro-opiomelanocortin （POMC） in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group， the model group showed significantly reduced MWT and PWL on day 3， 7， 10， and 14 （P＜0.01）. Compared with the model group， the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 （P＜0.05）. Compared with the Tuina group， the blockade group exhibited higher MWT on day 7， 10， and 14， and higher PWL on day 10 （P＜0.05）. Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group， while the model group exhibited myelin collapse， distortion， and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse， whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group， the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn （P＜0.05 or P＜0.01）. Compared with the model group， the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally， the Tuina group showed elevated levels of CD206， IL-10， and POMC， whereas the blockade group had decreased CD206 levels （P＜0.05）. ConclusionTuina at "Weizhong （BL 40）" alleviates neuropathic pain in CCI rats， potentially by regulating microglial activation in the spinal cord， inhibiting M1 polarization while promoting M2 polarization， and activating the IL-10/β-EP pathway to exert analgesic effects.

Aromatic Chinese medicinal essential oils are volatile oils extracted from aromatic Chinese herbs， which can prevent and treat respiratory infectious diseases through multiple synergistic mechanisms including pathogen inhibition， immune regulation， and inflammatory response regulation. Essential oils are primarily used externally on the body to prevent infections and alleviate symptoms through methods like inhalation， smearing， topical application， bathing， gargling or as a suppository. They can also be utilized in the environment for disinfection and air purification， through methods like diffusion， vaporization， or spraying. The external application of essential oils extracted from Chinese aromatic herbs has the advantages of convenience， quick absorption， and simultaneous influence on both the body and mind. However， there are still challenges and deficiencies in aspects such as the positioning of functions， indications， safety， and the research on the mechanism of action. It has been proposed to combine the theory of aromatic Chinese medicinals with the characteristics of essential oils， and formulate prescriptions of Chinese medicinal essential oils under the principles of traditional Chinese medicine syndrome differentiation， and prevent and treat respiratory infectious diseases efficiently， accurately， and safely， thereby expanding the clinical application of aromatic Chinese medicinals and the preventive theory of traditional Chinese medicine.

Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.

Antibody-drug conjugates (ADCs) are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker. Currently, 15 ADCs have been clinically approved worldwide. More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs. ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development. It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells, thereby producing promising antitumor efficacy and favorable adverse effect profiles. However, emergence of drug resistance has severely hindered the clinical efficacy of ADCs. In this review, we introduce the structure and mechanism of ADCs, describe the development of ADCs, summarized the latest research about the mechanisms of ADC resistance, discussed the strategies to overcome ADCs resistance, and predicted biomarkers for treatment response to ADC, aiming to contribute to the development of ADCs in the future.