ObjectiveTo observe the effect of Liuwei Dihuangwan on behavioral impairments in the rat model of autism spectrum disorder （ASD） and explore the mechanism of action. MethodsTwelve SD pregnant rats were intraperitoneally injected with valproic acid （VPA） （10 rats） or normal saline （2 rats）， and male offspring were selected to establish the model of ASD and the control rats. Rats were randomly assigned into model， low-dose （0.75 g·kg^-1） and high-dose （1.5 g·kg^-1） Liuwei Dihuangwan， vitamin D （positive drug， 3.7×10^-5 g·kg^-1）， and blank groups. Each group was administrated with the corresponding concentration of drugs or the same volume of normal saline by gavage for 2 weeks. After the intervention， the three-chamber social test was conducted to evaluate social interaction and social preference. The open field test was carried out to observe spontaneous behavior and anxiety state. Hematoxylin-eosin staining （HE） was used to observe the pathological changes of the prefrontal tissue. Transmission electron microscopy was employed to observe the ultrastructure of mitochondria in prefrontal neurons. Immunofluorescence was used to detect the expression of ionized calcium-binding adapter molecule-1 （Iba-1） in the prefrontal tissue. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was employed to assess the expression differences of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated Unc-51-like autophagy-activating kinase 1 （p-ULK1）， Unc-51-like autophagy-activating kinase 1 （ULK1）， and FUN14 domain-containing protein 1 （FUNDC1）. ResultsCompared with the blank group， the model group spent less time sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.01） and showed reductions in the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.01）. In addition， the model group showed extensive apoptosis of neurons， with shrunken nuclei and red-stained cytoplasm， and extensive necrosis of neurons in the prefrontal tissue， mitochondrial swelling， decreased matrix density， disrupted cristae， and autophagic lysosomes in neurons， increases in the rate of Iba-1 positive cells in the prefrontal area （P<0.01） and the levels of TNF-α and IL-6 （P<0.01）， and down-regulation in the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. Compared with the model group， low-dose and high-dose Liuwei Dihuangwan and the vitamin D prolonged the time spent sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.05， P<0.01）， increased the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.05， P<0.01）， restored the morphology of neurons in the prefrontal tissue， decreased the number of apoptotic cells， alleviated the swelling of mitochondria in neurons， increased the matrix density， mitigated the fragmentation and disorder of cristae， and increased the number of autophagosomes. Moreover， the drugs decreased the rate of Iba-1 positive cells in the prefrontal area （P<0.01）， lowered the levels of TNF-α and IL-6 （P<0.01）， and up-regulated the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. ConclusionLiuwei Dihuangwan ameliorate autism-like behaviors and reduce neuronal apoptosis and neuroinflammatory damage in the rat model of ASD by promoting mitophagy mediated by the AMPK/ULK1/FUNDC1 pathway.

The incidence and mortality of hepatocellular carcinoma (HCC) in China are among the highest in the world, imposing a heavy social burden. Liver resection and liver transplantation are the primary radical treatments for HCC, although most patients are no longer able to meet the surgical requirements at initial diagnosis. Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT) has the advantages of shrinking tumors, enlarging residual liver, regressing portal vein tumor thrombus and improving the quality of life, which can be used for conversion, downstaging and bridging therapy for HCC before surgical treatment, enabling patients regain the chance of radical treatment and reducing the postoperative recurrence rate. This review focuses on the clinical application and progress of ⁹⁰Y-SIRT in this field.

ObjectiveTo investigate the efficacy of Xingpi capsules （XPC） in treating diarrhea-predominant irritable bowel syndrome （IBS-D） with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free （SPF）-grade healthy rats were used as the normal control group. After successful modeling， SPF-grade rats were randomly divided into a model group， a pinaverium bromide group （1.5 mg·kg^-1）， and low- and high-dose XPC groups （0.135 and 0.54 g·kg^-1）， with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage， while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day， and the Bristol score was recorded. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of 5-hydroxytryptamine （5-HT） in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier， intestinal motility， and expression of related pathway proteins were evaluated by hematoxylin-eosin （HE） staining， immunohistochemistry， and Western blot. ResultsCompared with those in the normal control group， rats in the model group showed a significantly decreased body weight and increased diarrhea rate， diarrhea grade， and Bristol score （P<0.01）. HE staining revealed incomplete colonic mucosa in the model group， with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier， shedding and disappearance of microvilli， and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated （P<0.01）， and the levels of 5-HT in serum and colon tissue were elevated （P<0.01）. The small intestine propulsion rate significantly increased （P<0.01）， and the expression of contractile proteins Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 2 （ROCK2） in colon and phosphorylation of myosin light chain （MLC₂₀） were upregulated （P<0.01）. Compared with the model group， the treatment groups showed alleviated diarrhea， diarrhea-associated symptoms， and pathological manifestations of colon tissue to varying degrees. Specifically， high-dose XPC exhibited effectively relieved diarrhea， promoted recovery of colonic mucosal structure， significantly reduced congestion and edema， upregulated expression of Occludin and Claudin-5 （P<0.01）， decreased levels of 5-HT in serum and colon tissue （P<0.05，P<0.01）， significantly slowed small intestine propulsion rate （P<0.01）， and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC₂₀ （P<0.05，P<0.01）. ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction， and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.

Objective:To explore the relationship between general demographic characteristics,inflammatory indicators,nutritional indicators,pathological data and lymph node metastasis in endometrial cancer(EC)pa-tients,and to construct and validate a model for preoperative prediction of lymph node status in endometrial canc-er patients.Methods:The preoperative clinical data of 473 patients with EC who underwent surgical treatment in the Zhu Jiang Hospital of Southern Medical University from January 2010 to April 2024 were retrospectively ana-lyzed.The independent risk factors of lymph node metastasis of endometrial cancer were screened by univariate and multivariate Logistic regression analyses,and the nomogram prediction model was constructed by R soft-ware.The performance of the model was evaluated by the receiver operating characteristic(ROC)curve,calibra-tion curve and clinical decision curve.Results:Menopausal status,high grade biopsy pathology,CA125 ≥24.47U/ml,systemic immune inflammatory index(SII)≥710.91,and prognostic nutritional index(PNI)＜52.90 were in-dependent risk factors for lymph node metastasis in endometrial cancer(OR＞1,P＜0.05).The nomogram model constructed based on these five factors had an AUC of 0.853 in the training set and 0.871 in the test set.The cali-bration curve fitted well,and the clinical decision curve shows a positive benefit.Conclusions:The endometrial cancer lymph node metastasis prediction model constructed based on menopausal status,biopsy pathology,CA125,SII,and PNI has good accuracy and fit,with certain clinical application value.

Objective:To investigate the relationship between the radioresistance of anaplastic thyroid cancer (ATC) and the induction of epithelial-mesenchymal transition (EMT).Methods:Firstly, the radiotherapy sensitivity of differentiated thyroid cancer cells (TPC-1, FTC-133) and ATC cells (CAL-62, 8305C), and the protein levels of E-cadherin, N-cadherin and vimentin proteins after 6 Gy irradiation were detected. The changes in transcriptional levels before and after 4 Gy X-ray radiation of ATC cells were analyzed using mRNA sequencing. Then, the ATC radio-resistant cell models were constructed and validated, and the cell line with the highest radio-resistance was selected for subsequent experiments. Radio-resistant cells were classified into the control group (no treatment), EMT-inhibitor group (EMT-inhibitor-1 pre-treatment), Vactosertib group [transforming growth factor-β(TGF-β) inhibitor Vactosertib pre-treatment), and si-Snail group (knockdown of Snail gene by siRNA transfection), respectively. The expression level of EMT related proteins and TGF-β/Smad signaling pathway related proteins, the cloning efficiency, and the phosphorylated-histone H2A family member X (γH2AX) positive cells rate in the treatment groups and the control group were detected by Western blotting, clone formation assay, immunofluorescence, respectively, reflecting the changes in EMT level and DNA repair ability. Comparison between two groups was performed by Dunnett t-test. Comparison among multiple groups was conducted by one-way ANOVA. Results:The radiosensitivity of ATC cells were lower than that of differentiated thyroid cancer cells. After irradiation, the expression level of E-cadherin was low, those of N-cadherin and vimentin were high, EMT level was increased, and the expression levels of TGF-β/Smad signaling pathway-associated proteins were up-regulated in ATC cells. After use of EMT inhibitor, Vactosertib and Snail knockdown, the expression levels of EMT-associated proteins were down-regulated, cell survival fraction was declined, γH2AX positive cell rate was increased, DNA damage repair ability was weakened and the radiosensitivity was enhanced in radiotherapy-resistant ATC strains. Conclusions:The level of radiotherapy resistance in ATC cells is positively correlated with the EMT level, and the mechanism of radiotherapy resistance is related to the activation of the TGF-β/Smad/Snail pathway after irradiation.

OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

Objective:To report a case of pediatric infected maxillary mucocele and review relevant literature. Methods:A 3 years and 9 months old male patient was involved. He had nasal congestion and runny nose for 3 months. He usually has pus and occasional bloody nose. Physical examination: A red lump in the right nasal cavity with complete obstruction of the nasal passage. CT and MRI showed a right sinus mass. The patients WBC was 4.76×10⁸, and CRP<0.5 mg/L. Drainage and marsupialization were performed by endoscopy. Results:No purulent discharge was observed during follow-up, and the recovery was good. Conclusion:Enhanced CT or MRI shows typical circular enhancement shadows in infected maxillary mucocele. This indicates that endoscopic sinus surgery has a definite therapeutic effect. Drainage and marsupialization of maxillary mucocele are sufficient.
Humans ; Male ; Mucocele/surgery* ; Child, Preschool ; Endoscopy ; Maxillary Sinus

Repetitive transcranial magnetic stimulation (rTMS) is a rapid and effective therapy for major depressive disorder; however, there is significant variability in therapeutic outcomes both within and across individuals, with approximately 50% of patients showing no response to rTMS treatment. Many studies have personalized the stimulation parameters of rTMS (e.g., location and intensity of stimulation) according to the anatomical and functional structure of the brain. In addition to these parameters, the internal states of the individual, such as circadian rhythm, behavior/cognition, neural oscillation, and neuroplasticity, also contribute to the variation in rTMS effects. In this review, we summarize the current literature on the interaction between rTMS and internal states. We propose two possible methods, multimodal treatment, and adaptive closed-loop treatment, to integrate patients' internal states to achieve better rTMS treatment for depression.
Humans ; Transcranial Magnetic Stimulation/methods* ; Depressive Disorder, Major/physiopathology* ; Neuronal Plasticity/physiology* ; Brain/physiopathology*

ObjectiveTo investigate the potential targets and mechanisms of Draconis Sanguis (DS), a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl (D. Sanguis, Xue Jie), in the treatment of myocardial infarction (MI).MethodsWe explored the potential mechanisms of DS in the treatment of MI using network pharmacology, bioinformatic techniques, and transcriptomic analysis, followed by validation through in vivo and in vitro experiments.ResultsNetwork pharmacology and bioinformatic analyses identified five genes (Fpr1, Glul, Mme, Mmp9, and Pla2g7) as potential targets for MI treatment. Moreover, DS significantly ameliorated cardiac function, inflammatory responses, and MI-induced myocardial fibrosis in vivo. Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI. Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene. Furthermore, DS reduced the expression of Pla2g7 (P = .0009), NLRP3 (P = .003), interleukin-18 (P .001), and interleukin-1β (P = .004) mRNAs in vivo.ConclusionsThe results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response. This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.