ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

AIM: To detect the distribution and expression of vascular endothelial growth factor(VEGF)in radiation retinopathy(RR)through fluorescence targeted imaging.METHODS:Covalent binding of fluorescein FITC with VEGF antibody ranibizumab to prepare targeted fluorescent imaging probe ranibizumab-FITC. SD rats were randomly divided into three groups based on the principle of weight balance: a normal control group(Con group), a low-dose radiation group(10 Gy group), and a high-dose radiation group(30 Gy group). Medical linear accelerators and lead blocks were used to locally irradiate the rat eyeballs for modeling. Western blot and qRT-PCR were used to detect the expression levels of VEGF-A in each group and to screen for appropriate modeling dose. The inverted fluorescence microscope and the confocal microscope were used to observe the distribution of VEGF and imaging probes in the retinas of control and RR model group rats, and to verify the effectiveness of targeted probes.RESULTS:The expression level of VEGF-A in the retina of rats in the high-dose radiation group(30 Gy group)was higher than that in the normal control group(Con group). In early RR, VEGF expression was observed to be associated with microaneurysms and abnormal microvessels in the retina. VEGF accumulation was observed at the site of capillary wall damage. When retinal capillary endothelial damage occurred, targeted probes gathered on the outer surface of the vessel wall.CONCLUSION:The expression level of VEGF in the retina of RR model rats is elevated, and fluorescent targeted molecular imaging probes can detect the spatial distribution of VEGF at the microvascular lesions in the retina of RR rats.

This paper proposes a two-stage method integrating visual foundation models （VFM） and diffusion models. The segment anything model （SAM） as VFM is combined with the SegRefiner diffusion model to construct the SAM-SegRefiner framework for automated segmentation of edema， inflammation， and thrombus regions in histopathological images of hemorrhoidal tissue， providing a reproducible technical tool for the objective quantification of pathological morphology and its application in traditional Chinese medicine （TCM） syndrome research. Trained and validated on multi-center retrospective data， the SAM-SegRefiner model achieved an average pixel accuracy of 95.32% and a mean intersection over union （mIoU） of 66.81% on an independent test set， significantly outperfor-ming comparative models such as U-Net， MixU-Net， and SAM-Med2D， and also demonstrating robust cross-center generalization capability. Furthermore， by correlating the quantitatively segmented results from the model with the patients' TCM syndrome types， the potential associations between pathomorphological features and TCM syndrome differentiation have been explored. The analysis revealed no statistically significant differences in the degree of inflammatory infiltration and thrombus formation among different syndrome types， suggesting a complex relationship between local pathological changes and systemic syndrome manifestations.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective:To improve the understanding of patients with diffuse large B-cell lymphoma (DLBCL) with pulmonary cryptococcosis.Methods:The clinical data of 1 DLBCL patient with pulmonary cryptococcosis in the Central Hospital of Fengxian District of Shanghai in May 2023 were retrospectively analyzed, and the relevant literatures were reviewed.Results:This 75-year-old female patient was asymptomatic after 2 cycles of R-CHOP chemotherapy. The high-resolution CT of lung showed that lung nodules were progressively enlarged. Antibacterial treatment was ineffective. Pulmonary cryptococcosis was confirmed by bronchoalveolar lavage fluid (BALF) targeted high-throughput sequencing (tNGS) and cryptococcus capsular antigen (CrAg) detection. The central nervous system was not involved. And the long-term adequate-dose fluconazole was prescribed for 6 months, and the treatment against lymphoma was given synchronously. The lung nodule lesions reduced after antifungal therapy for 1 month. The lung nodules disappeared after the follow-up of 6 months after completion of final chemotherapy. The evaluation of lymphoma indicated complete remission.Conclusions:Pulmonary cryptococcosis occurs insidiously and shows no specific symptoms; its imaging manifestations are variable and routine anti-infection is ineffective. Immunochemotherapy for lymphoma patients is a high-risk factor for cryptococcal infection. tNGS and CrAg testing for BALF are effective methods of the confirmed diagnosis. The early and long-term adequate-dose antifungal treatment is the key to preventing the recurrence or progression.

Objective To evaluate and compare the long-term efficacy of endoscopic radiofrequency ablation(RFA)and photodynamic therapy(PDT)combined with biliary stenting for the treatment of unresectable extrahepatic cholangiocarcinoma.Methods Clinical data of patients with cholangiocarcinoma who received endoscopic RFA or PDT treatment from February 2018 to February 2023 were retrospectively collected.The patients were divided into RFA group(n=30,received endoscopic RFA combined with biliary stent placement)and PDT group(n=20,received PDT combined with biliary stent placement).The frequency of treatment,stent patency time,overall survival time and adverse events incidence were counted.The factors affecting the survival time of patients were analyzed.Results The overall survival time was 14.0(95%CI:11.8～16.2)months in RFA group and 18.0(95%CI:15.4～20.6)months in PDT group,the median patency time of stent was 4.0(95%CI:2.7～5.3)months in RFA group and 3.5(95%CI:2.3～4.7)months in PDT group,the differences were not statistically significant(P>0.05).Multivariate Cox regression analysis showed that the H＾R of patients with≥2 endoscopic RFA or PDT treatments was 2.417,which was a protective factor affecting overall survival(P=0.018),while the H＾R of TNM stage Ⅲ to Ⅳ was 0.300,which was a risk factor affecting the overall survival period(P=0.002).No significant difference was found in clinical success rate(both 100.00%)and adverse events incidence between the two groups[28.13%(9/32)vs.23.81%(5/21)],the difference was not statistically significant(P>0.05).Conclusion The long-term efficacy of endoscopic RFA or PDT combined with biliary stenting in the treatment of unresectable extrahepatic cholangiocarcinoma is comparable,while the sequential treatment of endoscopic RFA or PDT≥2 times can effectively prolong the overall survival of patients.

BACKGROUND:Exosomes derived from human umbilical cord mesenchymal stem cells are widely used for bone repair and reconstruction,significantly enhancing osteogenesis and promoting angiogenesis.OBJECTIVE:To explore the mechanisms of exosomes derived from human umbilical cord mesenchymal stem cells in the treatment of osteoporotic fractures.METHODS:H uman umbilical cord mesenchymal stem cells were extracted using tissue block culture method.Exosomes derived from human umbilical cord mesenchymal stem cells were extracted using ultracentrifugation method for identification.Thirty 12-week-old female SD rats were randomly divided into sham-operated group(n=6)and ovariectomized group(n=24).Osteoporosis model was established by castration in the ovariectomized group.12 weeks after modeling,6 rats in the ovariectomized group and 6 rats in the sham-operated group were randomly selected for Micro-CT and hematoxylin-eosin staining to verify the models.After verification,the remaining 18 rats in the ovariectomized group were randomly assigned to three groups to establish osteoporotic fracture models.The fracture end was separately injected with PBS(PBS group),exosomes at 1.5×1011 particles/mL(low-concentration exosome group),and 3×1011 particles/mL(high-concentration exosome group).Four weeks after operation,fracture healing and bone angiogenesis were evaluated by imaging and histological observations.RESULTS AND CONCLUSION:(1)In the gross specimens,compared with the PBS group,the exosome group had faster fracture healing and more callus formation.(2)The X-ray score of fracture healing in the exosome group was significantly higher than that in the PBS group,and the difference was significant(P＜0.05).(3)Micro-CT three-dimensional imaging:Compared with the PBS group,the fracture healing in the exosome group was accelerated and the callus formation was significantly increased;the bone volume fraction in the exosome group was significantly higher than that in the PBS group,and the difference was significant(P＜0.01).(4)Hematoxylin-eosin staining and Masson's trichrome staining showed that bone trabeculae and the new bone tissue in the exosome group were more than those in the PBS group.(5)Immunohistochemical staining showed that the expression of CD31 and osteocalcin in the exosome group was significantly higher than that in the PBS group.The high-concentration exosome group had a higher density of new blood vessels,more callus formation,and faster fracture healing than the low-concentration exosome group,showing a concentration-dependent manner.The results show that exosomes derived from human umbilical cord mesenchymal stem cells can promote the repair of osteoporotic fracture by enhancing the angiogenesis and osteogenesis.The mechanism may be related to the increased expression of CD31 and osteocalcin.

Objective:To explore the clinical features of Brucellar myelitis and diagnosis and treatment of secondary neuromyelitis optica spectrum disorder (NMOSD), and enhance the awareness of clinicians about this disease.Methods:A retrospective study was performed; 13 patients with Brucellar myelitis admitted to Department of Neurology, Inner Mongolia Autonomous Region People's Hospital from January 2020 to December 2024 were chosen. Clinical data were collected, and MRI images and serological changes during the infection period were observed. Serum and cerebrospinal fluid demyelinating antibody markers and cerebrospinal fluid oligoclonal bands (OCBs) in the suspected secondary inflammatory demyelinating diseases of the central nervous system patients were detected. All patients received standard antibiotic treatment and/or individualized immunotherapy depending on disease severity. The patients were followed up for 24 (12, 42) months. At the last follow-up, the neurological outcomes were evaluated using modified Rankin scale (mRS, scores of 0-2: good prognosis; scores of 3-6: poor prognosis).Results:(1) Among the 13 patients, 12 had motor disorder, 9 had bladder/bowel dysfunction, 7 had sensory abnormality, and 4 had other symptoms such as dizziness, behavioral changes, or unsteady gait. (2) MRI results showed that 8 patients had spinal cord abnormalities, including 2 with long-segment intramedullary high signal at T2-weighted image and 6 with short-segment local intramedullary high signal at T2-weighted image. Enhanced MRI was performed in 11 patients, with 2 showing lesion enhancement, 3 showing meningeal enhancement, and 6 showing no enhancement. (3) Four patients had elevated cerebrospinal fluid pressure (>180 mmH 2O); 9 patients had elevated cerebrospinal fluid protein level (>0.45 g/L). Brucella-specific DNA was detected in the cerebrospinal fluid of 6 patients. One patient was positive for OCB type II. One patient was positive for aquaporin 4 antibody (AQP4-IgG) in both serum and cerebrospinal fluid, and one patient was double positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG) and AQP4-IgG in serum. (4) All 13 patients received standard antibiotic treatment; 12 patients received immunotherapy. (5) Among the 4 patients with poor prognosis, 3 died and the remaining 9 had a good prognosis. The mRS score decreasing from 4 (3, 4) at admission to 2 (2, 3) at the last follow-up, showing an overall improvement in neurological function. (6) Among the 13 patients, 2 were diagnosed as having Brucellar myelitis secondary NMOSD. On the basis of antibiotic treatment, one AQP4-IgG positive patient was treated with high-dose glucocorticoids only and later died; one MOG-IgG and AQP4-IgG double positive patient was treated with intravenous immunoglobulin combined with high-dose glucocorticoids and sequential rituximab, with mRS score decreasing from 5 at admission to 2 at the last follow-up and good neurological function recovery. Conclusions:The clinical manifestations of Brucellar myelitis are diverse and overlap with the clinical features of NMOSD. For patients with suspected Brucellar myelitis secondary NMOSD, combination of immunosuppressant (such as rituximab) with antibiotics may be an effective individualized treatment.