ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

It is believed that there is a pathogenesis of yang deficiency in polycystic ovary syndrome （PCOS） infertility， and it is concluded that warm-yang method has a better effect in improving endometrial abnormality， enhancing the quality of follicles， correcting endocrine disorders， and resolving or alleviating clinical symptoms in PCOS infertility. Based on Yanghe Decoction （阳和汤）， a representative traditional Chinese medicine decoction for warming yang， Yanghe Xiaonang Decoction （阳和消囊汤） was formulated， combining with warm medicinals according to symptoms， and aerobic exercise was also advocated to help generate and develop yang qi， in order to provide ideas for clinical treatments.

BACKGROUND:It has been elucidated that downregulation of nuclear enriched abundant transcript 1(NEAT1)inhibits the progression of keloid fibroblasts,but the exact mechanism is not fully understood. OBJECTIVE:To investigate the influences of long non-coding RNA nuclear enriched abundant transcript 1(lncRNA NEAT1)on the proliferation,apoptosis and migration of keloid fibroblasts by regulating the miR-136-5p/ubiquitin-specific protease 4(USP4)axis. METHODS:Keloid fibroblasts were divided into five groups:si-NC group,control check group,si-NEAT1 group,si-NEAT1+miR-136-5p inhibitor group,and si-NEAT1+inhibitor-NC group.qRT-PCR was performed to measure the expressions of NEAT1 and miR-136-5p;cell counting kit-8 assay and EDU staining were performed to measure cell proliferation;flow cytometry was performed to measure apoptosis;scratch-healing experiment was performed to measure cell migration;western blot assay was performed to measure the protein expressions of USP4,p27,Bax,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain;dual-luciferase assay was performed to examine the relationship of NEAT1 with miR-136-5p as well as the relationship of miR-136-5p with USP4. RESULTS AND CONCLUSION:Compared with the si-NC group,the NEAT1 expression,absorbance value at 450 nm,percentage of EDU positive cells,scratch-healing rate,the protein expressions of USP4,matrix metalloproteinase-9,α-smooth muscle actin,and type I collagen α1 chain decreased in the si-NEAT1 group(P<0.05),while the expression of miR-136-5p,apoptosis rate,and the protein expressions of p27 and Bax increased(P<0.05).miR-136-5p inhibitor reversed the effect of silencing NEAT1 on the biological behavior of keloid fibroblasts.There was a targeted regulatory relationship between NEAT1 and miR-136-5p as well as between miR-136-5p and USP4.To conclude,silencing NEAT1 may inhibit the proliferation and migration of keloid fibroblasts and induce apoptosis by regulating the miR-136-5p/USP4 axis..

Objective To explore the effect of metformin combined with insulin detemir on intestinal flora in patients with gestational diabetes mellitus (GDM). Methods A total of 176 patients with GDM admitted to Luzhou People's Hospital from May 2022 to July 2023 were selected and randomly divided into a single drug group and a combined group, with 88 cases in each group. The single drug group was treated with insulin detemir, and the combined group was given metformin combined with insulin detemir. The glucose metabolism levels and intestinal flora distribution were compared between the two groups before treatment and during delivery. The maternal-infant outcomes were statistically analyzed and compared between the two groups. Results During delivery, the levels of fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc), and largest amplitude of glycemic excursions (LAGE), and the contents of Enterobacterium, Enterococcus and Escherichia coli in both groups were reduced compared with those before treatment, and the above indicators in the combined group were lower than those in the single drug group (all P<0.05). The contents of Bifidobacterium and Lactobacillus were increased in both groups, and the indicators were higher in the combined group than those in the single drug group (all P<0.05). There was no significant difference in adverse maternal-infant outcomes between the two groups (P>0.05). Conclusion Metformin combined with insulin detemir can effectively reduce blood glucose levels and improve intestinal flora distribution in patients with GDM, without increasing adverse maternal-infant outcomes.

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

Objective Idiopathic rolandic epilepsy syndrome （IRES） is the most common epilepsy syndrome in childhood， and its lesion site remains undetermined. This article aims to investigate the source of epileptiform discharges in IRES using magnetoencephalography （MEG）.Methods A total of 70 patients with IRES were enrolled in this prospective MEG-based study， among whom there were 53 children with benign epilepsy of childhood with centrotemporal spikes （BECTS）， 12 children with atypical benign partial epilepsy （ABPE）， 3 children with Landau-Kleffner syndrome （LKS）， and 2 children with epileptic encephalopathy with continuous spike-and-waves during slow-wave sleep （CSWS）. Epileptiform discharges were collected independently from each patient 10 times， and an MEG source analysis was performed. Standardized low-resolution brain electromagnetic tomography was used to perform source localization of the distributed source model. The spike source density was quantified into amplitude， and source location was determined according to the Desikan-Killiany atlas. The association between the distribution of spike source in brain and clinical manifestations was analyzed.Results In IRES， there were significant differences in the source locations of epilepsy discharge between BECTS， ABPE， LKS， and CSWS. The current source density of CSWS was stronger in the frontal lobe， the temporal lobe， and the anterior cingulate gyrus， while that of ABPE was stronger in the frontal lobe， and that of BECTS and LKS were stronger in the temporal lobe. The more severe phenotype of epilepsy， such as generalized tonic-clonic seizure， was associated with a stronger current source density in the brain， which was consistent with electroencephalography manifestations.Conclusion This study identifies different sources of epileptiform discharges in IRES. The density distribution of these spike sources may help to explain the discharge， cognitive， and neuropsychological characteristics in different subtypes of IRES.
Magnetoencephalography

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease. It has been reported in the literature that COPD patients with chronic airway mucus hypersecretion have more frequent acute exacerbations, more severe lung function decline, and higher hospitalizations and mortality. Therefore, it is particularly critical to understand the pathogenesis of hypersecretion of mucus in chronic obstructive pulmonary disease and find out effective treatment. This article focuses on the structure, significance of airway mucus and the mechanism of hypersecretion of mucus in chronic obstructive pulmonary disease (COPD). In addition, we also summarized drug and non-drug therapy for chronic airway mucus hypersecretion in this article. Drug therapy includes traditional drug therapy, some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy, and non-drug therapy includes smoking cessation, physical therapy and bronchos-copy therapy. We hope that it will provide new ideas and directions for the treatment of mucus hypersecretion in COPD patients.

OBJECTIVE To study the ameliorative effect and potential mechanism of curcumin on diabetes model rats with depression based on cAMP response element binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathway. METHODS The diabetes model rat with depression was established by high fat and high sugar diet+intraperitoneal injection of streptozotocin+chronic unpredictable stress-induced depression. The successfully modeled rats were randomly divided into model group， positive control group （0.18 g/kg metformin and 1.8 mg/kg fluoxetine， gavage）， curcumin low-dose and high-dose groups （30， 60 mg/kg， gavage） and curcumin high-dose+CREB inhibitor group [60 mg/kg curcumin （gavage）+5 mg/kg CREB inhibitor 666-15 （intraperitoneal injection）]， with 12 rats in each group. Another 12 healthy rats were selected as the normal group. Each group was given a corresponding intervention for 4 weeks， the fasting blood glucose level of rats was detected， and the depression of rats was assessed. The levels of corticosterone （CORT） and inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin- 1β （IL-1β）， IL-6] in serum， and the levels of norepinephrine （NE） and 5-hydroxytryptamine （5-HT） in hippocampal tissue were determined. The pathological changes and neuronal apoptosis were observed in the hippocampal tissue of rats in each group； the expression levels of CREB， BDNF mRNA and protein in hippocampal tissue were detected. RESULTS Compared with the normal group， the hippocampal tissue of rats in the model group was severely damaged， and neurons were scattered， while the fasting blood glucose， the forced swimming immobility time， the tail suspension immobility time， serum levels of CORT， TNF-α， IL-1β and IL-6， and neuron apoptosis indexes were all increased or prolonged significantly （P＜0.05）. The levels of NE and 5-HT， the number of surviving neurons， and the expression levels of CREB and BDNF mRNA and protein in hippocampal tissue were decreased significantly （P＜0.05）. Compared with the 的model group， the damage to hippocampal tissue was relieved in the positive control group and curcumin groups， while the above indexes were improved significantly （P＜0.05）. The improvement effect of curcumin high-dose group was better than that of curcumin low-dose group （P＜0.05）. CREB inhibitor could significantly reverse the ameliorative effect of high-dose curcumin on the model rats （P＜0.05）. CONCLUSIONS Curcumin can improve the depression of diabetes model rats with depression， and relieve neuronal damage and inflammatory response， the mechanism of which may be associated with activating CREB/BDNF signaling pathway.