OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

BACKGROUND: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited. Notably, artificial intelligence (AI) technologies have significantly advanced drug discovery. This study aimed to discover RIPK3 inhibitor with AI assistance. METHODS: An acute ocular hypertension model was used to simulate pathological ocular hypertension in vivo . We employed a series of AI methods, including large language and graph neural network models, to identify the target compounds of RIPK3. Subsequently, these target candidates were validated using molecular simulations (molecular docking, absorption, distribution, metabolism, excretion, and toxicity [ADMET] prediction, and molecular dynamics simulations) and biological experiments (Western blotting and fluorescence staining) in vitro and in vivo . RESULTS: AI-driven drug screening techniques have the potential to greatly accelerate drug development. A compound called HG9-91-01, identified using AI methods, exerted neuroprotective effects in acute glaucoma. Our research indicates that all five candidates recommended by AI were able to protect the morphological integrity of RGC cells when exposed to hypoxia and glucose deficiency, and HG9-91-01 showed a higher cell survival rate compared to the other candidates. Furthermore, HG9-91-01 was found to protect the retinal structure and reduce the loss of retinal layers in an acute glaucoma model. It was also observed that the neuroprotective effects of HG9-91-01 were highly correlated with the inhibition of PANoptosis (apoptosis, pyroptosis, and necroptosis). Finally, we found that HG9-91-01 can regulate key proteins related to PANoptosis, indicating that this compound exerts neuroprotective effects in the retina by inhibiting the expression of proteins related to apoptosis, pyroptosis, and necroptosis. CONCLUSION AI-enabled drug discovery revealed that HG9-91-01 could serve as a potential treatment for acute glaucoma.
Animals ; Glaucoma/metabolism* ; Neuroprotective Agents/pharmacology* ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Artificial Intelligence ; Retinal Ganglion Cells/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Male

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

The high prevalence of childhood caries poses a considerable threat to children's overall health. Traditional Chinese medicine (TCM) concepts offers a distinctive and valuable perspective on caries prevention. This study explores TCM's conceptualization of dental caries in relation to the physiological characteristics of children and proposes targeted preventive strategies, including holistic care, dietary regulation, and lifestyle modification. In addition, the study highlights the role of traditional modalities, such as Chinese herbal medicine, acupuncture, moxibustion, and tuina, in caries prevention, while emphasizing the importance of supporting children's mental health. The integration of TCM with modern medical practices holds promise for advancing research into the prevention and treatment of caries. Furthermore, promoting the overall improvement of children's health.
Dental Caries/prevention & control* ; Humans ; Medicine, Chinese Traditional ; Child ; Acupuncture Therapy ; Moxibustion ; Life Style ; Drugs, Chinese Herbal/therapeutic use*

Objective To systematically compare the perioperative outcomes of robot-assisted transvaginal natural orifice transluminal endoscopic surgery total hysterectomy(R-vNOTES-TH),transvaginal natural orifice transluminal endoscopic surgery total hysterectomy(vNOTES-TH),and robot-assisted laparoendoscopic single-site total hysterectomy(R-LESS-TH),and to evaluate the clinical advantages of R-vNOTES-TH.Methods Clinical data of 259 patients undergoing total hysterectomy for benign diseases at Zhongnan Hospital of Wuhan University from Jan.2020 to Dec.2024 were retrospectively analyzed.Baseline indicators and perioperative indicators were collected.Patients were assigned to 3 groups according to the surgical approach:R-vNOTES-TH group(n=22),vNOTES-TH group(n=39),or R-LESS-TH group(n=198).Perioperative indicators were compared between the R-vNOTES-TH group and the other 2 groups to evaluate the advantages of R-vNOTES-TH.Results Compared with the vNOTES-TH group,the R-vNOTES-TH group had significantly less intraoperative blood loss(50[50,100]mL vs 100[50,100]mL,P=0.027),lower intraoperative fluid infusion volume(1 000[500,1 000]mL vs 1 000[1 000,1 500]mL,P＜0.001),and shorter urinary catheter indwelling time(3[1,4]d vs 5[2,5]d,P=0.043),but longer vaginal drain indwelling time(2[2,3]d vs 2[0,2]d,P=0.004).Compared with the R-LESS-TH group,the R-vNOTES-TH group had longer urinary catheter indwelling time(3[1,4]d vs 1[1,1]d,P＜0.001).Conclusion Compared with vNOTES-TH,R-vNOTES-TH enhances intraoperative operational precision,reduces bleed loss,and accelerates urinary catheter removal,confirming that the robotic system effectively overcomes the technical limitations of conventional vNOTES.Although R-vNOTES-TH eliminates abdominal wall trauma-thereby prolonging urinary catheter indwelling time relative to R-LESS-TH-it offers patients a truly scar-free alternative.

Objective The present situation and hotspots of KM mouse research were visualized by CiteSpace software,which provided a reference for breaking through the bottleneck of KM mouse research and finding new ideas in China.Methods A total of 3981 articles were retrieved from CNKI and Web of Science databases from January 1,2004 to June 10,2023,of which the number of publications,countries(regions),institutions,author cooperation network,keyword co-occurrence,clustering,burst words,and cited English literature for analysis.Results The number of documents published in Chinese was decreased and the number of documents published in English was increased gradually in KM mouse research.The three countries with the most published articles were China,the United States,and Japan,where the leading research institutions were the China Agricultural University,Chinese Academy of Sciences,and Nanjing University of Chinese Medicine.The main authors at home and abroad were Liu Weihui,Li Guangwu,and Zhao Xin.The domestic research focused on the toxicology,immunology,and reproduction of KM mouse,and the foreign research focused on the cell biology and physiology of KM mouse.Conclusions KM mouse have been used and popularized in our country for more than 70 years,mainly focusing on toxicology,immunology,and reproduction.Although the use of KM mouse has led tove made allowed some achievements in experiments,certain it is necessary to solve their problems in the future,such as the standardization of population breeding,the discovery of the dominant research fields,and the further promotion of animal ethics,should be resolved.

Objective Using literature metrology,scientific literature in the field of depression models in animals was analyzed to better understand the development trends and hot topics in this field.Methods We obtained publications on depression and animal models from 2013 to 2022 from the Web of Science core set database.CiteSpace 6.1 R1(64-bit)Basic was used to analyze annual publications,countries,institutions,authors,and keywords related to this field.Results A total of 1000 articles were included in this study.From 2013 to 2022,the number of articles published increased gradually and then stabilized.In terms of the number of articles,the United States had the most published articles(256).Wegener Gregers was the most influential author in the field with 23 published articles.Conclusions The field focuses on signaling pathways and therapeutic approaches to determine the pathogenesis of depression and better treatments.This study provides a visual analysis of trends in depression research to help researchers keep up with the latest developments.

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) in reduction of renal ischemia-reperfusion (I/R) injury by the human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes (hucMSCs-exo) in mice.Methods:The hucMSCs were cultured, and exosomes were extracted and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Thirty-six male SPF-grade C57BL/6 mice, weighing 20-25 g, were used. Thirty mice were selected and divided into 5 groups ( n=6 each) by a random number table method: sham operation group (Sham group), sham operation + Nrf2 inhibitor ML385 group (Sham + ML385 group), renal I/R group (I/R group), renal I/R + exosome group (I/R+ EXO group), and renal I/R + exosome + Nrf2 inhibitor ML385 group (I/R+ EXO+ ML385 group). A model of renal I/R injury was prepared by clamping the bilateral renal pedicles for 45 min followed by perfusion in anesthetized animals. ML385 30 mg/kg was intraperitoneally injected at 45 min before preparing the model in Sham+ ML385 group and I/R+ EXO+ ML385 group, and hucMSCs-exo 100 μg was injected via the tail vein at 15 min before reperfusion in I/R+ EXO group and I/R+ EXO+ ML385 group. Serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were detected at 24 h of reperfusion. The renal tissues were obtained for examination of the pathological changes and for determination of contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels and expression of Nrf2 and HO-1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The left 6 mice were allocated to sham operation group (Sham-IM group, n=3) and renal I/R group (I/R-IM group, n=3) by a random number table method for VISQUE in living imaging observation. Results:The exosomes showed a typical cup-shaped morphology with a transmission electron microscope, the nanoparticles tracked and analyzed the average diameter of the exosome, with an average diameter of 96.7 nm, and the positive expression of surface markers CD9, CD63 and TSG101 was detected using Western blot. The renal fluorescence intensity value was significantly increased in I/R-IM group as compared with Sham-IM group ( P<0.05). Compared with Sham group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R group, and no significant change was found in serum BUN and Cr concentrations in Sham+ ML385 group ( P>0.05). Compared with I/R group, the serum BUN and Cr concentrations were significantly decreased, the contents of IL-6, TNF-α and MDA and ROS levels were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 protein and mRNA was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in I/R+ EXO group. Compared with I/R+ EXO group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R+ EXO+ ML385 group. Conclusions:The mechanism by which hucMSCs-exo reduces renal I/R injury may be related to activation of the Nrf2/HO-1 signaling pathway in mice.

Objective To investigate the correlation between gene polymorphisms of coagulation factor Ⅻ(FⅫ)rs1801020 and resistin rs1862513 and unexplained recurrent spontaneous abortion(URSA).Methods A total of 189 patients diagnosed with URSA and 191 healthy postpartum women during the same period were selected from the obstetric clinic of Changning Maternity and Infant Health Hospital from January 2020 to December 2022.The probe PCR was used to detect gene polymorphisms of rs1801020 and rs1862513 in peripheral blood,and the differences in genotype distribution between the groups were observed.Results The frequencies of geno-types and alleles for F Ⅻ rs1801020 in the URSA-A group were 4.9％(CC),35.7％(CT),59.5％(TT),22.7％(C),and 77.3％(T),respectively.In the control A group,the frequencies were 8.0％(CC),47.1％(CT),44.9％(TT),31.5％(C)and 68.5％(T).The frequencies of genotypes and alleles for resistin rs1862513 in the URSA-B group were 11.3％(CC),47.3％(CG),41.4％(GG),34.9％(C)and 65.1％(G).In the control B group,the frequencies were 10.2％(CC),34.1％(CG),55.7％(GG),27.3％(C)and 72.7％(G).There was no significant difference in genotype frequency of the two loci(P＞0.05),but there was a sig-nificant difference in allele frequency(P＜0.05).The distribution frequency of F Ⅻ rs1801020 T allele in the URSA group was higher than that in the control group(X2=6.32,OR=1.567,95％CI:1.100-2.238,P=0.012).The distribution frequency of resistin rs1862513 G allele in URSA group was lower than that in con-trol group(X2=4.96,OR=1.433,95％CI:1.050-1.969,P=0.026).The mutation of F Ⅻ rs1801020 C to T was a risk factor for the occurrence of URSA,while the mutation of rs1862513 C to G was a protective factor for the occurrence of URSA(P＜0.05).The combined genotype analysis showed that compared to the popu-lation carrying the rs1801020 CC+rs1862513 CC genotype combination,the population carrying the rs1801020 TT+rs1862513 CG genotype had a significantly higher risk of URSA(OR=5.684,95％CI:1.210-30.920,P=0.035).Conclusion FⅫ rs1801020 T allele may increase the risk of URSA and resistin rs1862513 G al-lele may the risk of URSA.People with rs1801020 TT+rs1862513 CG genotype combination is more likely to develop URSA than those with rs1801020 CC+rs1862513 CC genotype combination.

Objective:To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with tislelizumab and tyrosine kinase inhibitor (TKI) as a conversion therapy in patients with initially unresectable hepatocellular carcinoma (HCC).Methods:The clinical data of 51 initially unresectable HCC patients admitted to the Department of Hepato-Pancreato-Biliary Surgery, the Eighth Affiliated Hospital of Guangxi Medical University from March 2022 to November 2023 were prospectively collected, including 46 males and 5 females, aged (53±11) years old. All patients received TACE combined with tislelizumab and TKI. For initially unresectable HCC patients who have successfully undergone conversion therapy, surgical resection was performed sequentially. Follow-up was conducted through regular outpatient visits or hospitalization combined with telephone contact, and the surgical conversion, relapse-free survival and adverse reactions of patients were recorded.Results:Among the 51 patients with initial unresectable HCC, there were 12 cases of stage Ib, 14 cases of stage IIa, 10 cases of stage IIb, and 15 cases of stage IIIa in Chinese liver cancer staging. The 51 patients were evaluated according to the modified solid tumor response evaluation criteria, and 15 patients had complete response, 26 had partial response, 5 had stable disease, and 5 had disease progression. The objective response rate was 80.4% (41/51), and the disease control rate was 90.2% (46/51). The conversion success rate was 49.0% (25/51), 2 patients gave up surgery, and the actual conversion rate was 45.1% (23/51). Among the 23 patients who underwent surgical resection, irregular hepatectomy was performed in 11 cases, lobectomy in 8 cases, and hemihepatectomy in 4 cases. Common treatment-related adverse events were hand-foot syndrome, hypertension, gingival bleeding, etc. Most of the drug-related adverse events were grade 1 to grade 2. A total of 10 patients (19.6%, 10/51) had grade 3 drug-related adverse events, and no grade 4 or above adverse events occurred, and no treatment-related deaths occurred. The cumulative recurrence free survival rates of 23 patients with initial unresectable HCC at 6 and 12 months after sequential hepatectomy were 100% and 94.7% respectively.Conclusion:The triple combination therapy of TACE combined with tislelizumab and TKI in the treatment of initial unresectable HCC has good clinical efficacy, and the adverse reactions are safe and controllable.