Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Autism spectrum disorder （ASD）， also known as autism， is a series of neurodevelopmental disorders characterized by social disorders and repetitive stereotyped behaviors/narrow interests. Its pathogenesis is complex， and there is a lack of effective treatment drugs， with some cases having adverse outcomes. Recent studies have consistently revealed that individuals with autism spectrum disorder （ASD） commonly exhibit characteristics such as gut microbiota dysbiosis （abnormal Bacteroidetes/Firmicutes ratio）， impaired intestinal barrier function （elevated serum levels of zonulin and LPS）， and intestinal immune dysregulation （increased pro-inflammatory cytokines including IL-6 and TNF-α）， suggesting that gastrointestinal abnormalities may influence central nervous system development through neuroendocrine， immunoregulatory， and metabolic pathways. Consequently， growing scholarly attention has focused on dietary interventions as potential approaches to alleviate clinical symptoms in children with ASD. This review systematically summarizes the role of gut microbiota and their metabolite alterations in ASD pathogenesis， along with recent advancements in understanding the microbiota-gut-brain axis mechanisms. Additionally， it elaborates on the therapeutic effects and underlying biological basis of restrictive diet therapy， modified diet therapy， and nutritional supplementation therapy in promoting the health of children with ASD. This systematic review reveals that children with ASD exhibit significant gut microbiota dysbiosis （e.g.， increased Clostridium， decreased Faecalibacterium） and abnormal metabolite profiles （e.g.， altered short-chain fatty acid spectra， elevated 4EPS levels）. These alterations exacerbate neuroinflammation and immune dysregulation through the microbiota-gut-brain axis， thereby impacting nervous system development and function. Furthermore， interventions such as ketogenic diets， camel milk， and specific nutritional supplements can alleviate certain ASD symptoms by modulating gut microbiota， restoring intestinal barrier function， and improving metabolic pathways. Future investigations should aim to create multi-omics evaluation systems for pinpointing potential beneficiaries， devise individualized intervention strategies rooted in microbiome characteristics， and verify their therapeutic value and safety in large-scale randomized controlled trials. These efforts are crucial to transitioning ASD treatment from symptomatic control to address disease etiology， thereby paving the way for improving prognoses.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

Objective:To establish a novel in vivo and in vitro model of type 2 endoleaks (T2EL) after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA).Methods:In vitro model: Using 3Dmax (2022) software, models of AAA and T2EL were created. These models were fabricated using 3D printing technology, with quartz as the material. Fresh pig blood was injected into the models, and a circulation system was established using a peristaltic pump. The direction of blood flow was observed to confirm the establishment of the in vitro T2EL model. In vivo model: Six Bama miniature pigs were selected, each 10 months old and weighing 40-50 kg. After determining whether unilateral iliac artery occlusion could be permanent through experiments, an AAA animal model from the end of the abdominal aorta to the left common iliac artery was created using the patch formation method. EVAR was performed through the right femoral artery, completely occluding the left iliac artery. The T2EL model was established by using the retrograde blood flow from the left iliac artery. The formation of AAA and T2EL models in vivo was confirmed by color Doppler ultrasound, digital subtraction angiography (DSA), and other methods. The measurement data with normal distribution were expressed as mean±standard deviation( ± s), and comparisons between groups were performed using the independent-samples t-test. The comparison between groups of count data was conducted using the chi-square test. Results:The successful establishment of the T2EL model was confirmed by observing the blood flow in the circulating drip flask. The weight of the Bama miniature pigs in the in vivo model was (41.33±2.21) kg, the diameter of the abdominal aorta was (7.45±0.15) mm, and the maximum diameter of the aneurysm was (16.67±0.61) mm. Through experiments, it was determined that the left iliac artery and umbilical artery of the experimental pigs could be isolated. Therefore, after the aneurysm from the end of the abdominal aorta to the left common iliac artery was established, a covered stent was implanted from the abdominal aorta to the right common iliac artery for EVAR treatment. The successful establishment of the AAA model and the T2EL model with the left iliac artery as the main "culprit vessel" was confirmed by color Doppler ultrasound and DSA.Conclusion:The in vitro models established through 3D printing technology and the T2EL animal model with the left iliac artery as the main "culprit vessel" have a high success rate and can serve as a model basis for the mechanism and treatment research of T2EL after EVAR for AAA.

This paper Summarizes the experience of national renowned Chinese medical practitioner professor YANG Jun in treating lumbar pain with acupuncture and moxibustion.In the view of professor YANG Jun,the etiology of lumbar pain is various and the pathogensis is complex,of which mainly related to be invaded by external pathogen,meridians obstructing blockage,kidney deficiency due to elderly,less of moistening due to kidney essence deficiency,sprain caused by fall and strike,and blood stasis obstructing meridians,and the syndrome differentiation of lumbar pain usually involves cold-damp obstructing blockage,kidney essence deficiency,and blood stasis blocking collaterals.The waist is the residence of kidney,kidney meridian runs through the spine and connecting it to the kidney,the bladder meridian locates on both sides of the spine and connecting it to the kidney,the circulation of governor vessel(GV)to the kidney,so the pathogensis of lumbar pain is closely related to kidney,bladder meridian,governor vessel.The basic pathogensis of lumbar pain is meridian qiand blood stasis stagnation,or the meridian less of moistening due to kidney essence deficiency,both of which cause pain.The main therapeutic principle for lumbar pain should be focusing on mind-regulating and meridians-dredging,cold-dispersing and damp-removing,kidney-boosting and blood-activating,as well as collateral-unblocking and pain-relieving,combining the lumbosacral spinal tri-needling,regulating the bladder meridian with moxibustion and electro-acupuncture,thus to achieve the optimal quantitative and effective state.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

This paper introduces Professor Zhang Qingping's clinical experience in treating post-stroke spastic paralysis.In the view of Professor Zhang Qingping,the main pathogenesis of post-stroke spastic paralysis being deficiency of yang qiand malnutrition of meridian-sinew,such diseases can be treated from the perspective of sinew theory.Professor Zhang addressed importance to acupoints selection of yin meridians and therapeutic sequence,and skilled in applying superficial-skin needling and multi-direction needling,she also emphasizes on seizing the opportunity to treat disease and regulating body and mind simultaneously,and obtained certain clinical effects in the treatment of post-stroke spastic paralysis.

This article systematically summarizes the clinical experience of Professor Yang Jun,a nationally renowned traditional Chinese medicine(TCM)physician,in applying refined direct moxibustion(applying a moxibustion pen made by Chinese medical extract)to treat functional dyspepsia(FD)of the stuffiness-fullness type.Based on decades of clinical practice,Professor Yang innovatively established a moxibustion therapy system for FD,which centers on TCM syndrome differentiation and treatment.The system emphasizes the refined identification of epigastric stuffiness and fullness syndrome,particularly focusing on the relative significance of abdominal distension and poor appetite.Its therapeutic features lie in establishing the principle of"prioritizing mind regulation while holistically harmonizing body and spirit",combined with personalized moxibustion dosage control and a unique refined direct moxibustion technique.By optimizing the configuration of each step in moxibustion therapy,the system maximizes therapeutic efficacy,providing novel theoretical foundations and clinical strategies for moxibustion treatment of stuffiness-fullness type of FD.

This article introduces Professor Yang Jun's clinical experience in treating bronchial asthma using warming needle moxibustion via the governor vessel-unblocking and conception vessel-regulating method.Professor Yang posits that asthma pathogenesis-whether triggered by internal imbalances or external pathogens-ultimately stems from yin-yang disharmony leading to rebellious lung qi and impaired diffusion/descending functions.Thus,restoring dynamic yin-yang balance constitutes the core therapeutic principle.As the governor and conception vessels govern the body's yin-yang regulation,Professor Yang's decades of clinical practice substantiate that"harmonizing these vessels determines life's vitality".His protocol combines warming needle moxibustion with press needles to activate governor-conception vessel functions,achieving five therapeutic effects:(1)yin-yang harmonization,(2)qi movement regulation,(3)meridian unblocking,(4)visceral stabilization,and(5)pathogen elimination,demonstrating remarkable efficacy.