OBJECTIVE To systematically evaluate the quality of the Heat-clearing and symptom-relieving formula and screen potential marker components that influence the quality of the formula. METHODS The contents of 11 components （calycosin-7- O - β -D-glucoside， ononin， hyperoside， isoquercitrin， baicalin， baicalein， cryptotanshinone， tanshinone Ⅱ A ， tanshinone Ⅰ， senkyunolide A， ferulic acid） in the Heat-clearing and symptom-relieving formula were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. Using the contents of the aforementioned components as variables， cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were conducted using OriginPro 2024 software and SIMCA 14.1 software； marker components affecting the quality of the Heat-clearing and symptom-relieving formula were then screened based on the criteria of variable importance in the projection （VIP） value＞1 and P ＜0.05. The comprehensive evaluation of 20 batches of samples was carried out using the entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） and grey correlation analysis （GCA） methods. RESULTS The contents of the above 11 components were 7.993-72.866， 4.542-31.228， 727.666-1 901.884， 496.846-1 293.279， 1 995.501-6 779.150， 54.500-241.280， 150.302-304.339， 79.698-189.206， 257.118-682.418， 5.498-21.687， 7.524-26.935 μg/g. CA， PCA and OPLS-DA results showed that 20 batches of samples were grouped into 2 categories. Q1， Q3， Q4， Q7-Q9， Q12， Q15， Q16 were grouped into one category， and the rest were grouped into another category； VIP values of ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin were all greater than 1 （ P ＜0.05）. Both the entropy weight-TOPSIS and GCA methods showed that the samples ranked in the top 11 according to the euclidean distance and relative correlation degree were Q2， Q5， Q6， Q10， Q11， Q13， Q14， Q17-Q20. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate and highly sens itive. Combined with chemical pattern recognition analysis， entropy weight-TOPSIS and GCA methods， this method can be used to evaluate the quality of the Heat-clearing and symptom-relieving formula. Ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin may be the marker components that affect the quality of this formula. The overall quality of 11 batches of the Heat-clearing and symptom-relieving formula， including Q17， is relatively superior.

The present study aimed to establish an LC-MS/MS method for the quantification of tiamulin in minipig plasma and to further conduct a pharmacokinetic comparison of different formulations. The plasma samples were extracted with acetonitrile (meloxicam as internal standard), separated on a C18 column, and quantified by multiple reaction monitoring mode (ESI+). Sanyuan minipigs were used as experimental animals. Plasma samples were collected after intravenous injection (10 mg/kg) and intragastric administration (20 mg/kg). The method showed good linearity, with intra- and inter-batch RSD of 1.00%–8.13% and RE within ±15%. The extraction recovery, matrix effect and stability of the analytical methods met the relevant requirements. Tiamulin fumarate active pharmaceutical ingredient was intravenously administered, with c0 of about (4383.73±2676.78) ng/mL, AUC0-t of about (4803.50±965.68) h·ng/mL, t1/2 of about (4.66±1.68) h, and CL of about (2.14±0.46) L/(kg·h). Three tiamulin formulations were intragastrically administered, with cmax of (552.00±328.55), (545.00±136.97) and (590.60±237.02) ng/mL, tmax of (1.47±0.68), (0.69±0.75) and (0.72±0.72) h, and F of 24.85%, 15.28% and 16.97%, respectively. The validated method meets the requirements for biological sample analysis and is applicable for the pharmacokinetic evaluation of tiamulin formulations in minipigs.

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.

Portal hypertension(PH)is one of the most common complications of chronic liver disease,which can lead to gastroesophageal varices,spontaneous portosystemic shunt,ectopic varices and sinistral PH.The formation mechanisms,imaging characteristics,diagnosis and clinical management of collateral circulation in PH were reviewed in this article.

BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes are involved in multiple injury repair processes,and the effects and the specific mechanisms of renal ischemia/reperfusion injury have not been fully elucidated.OBJECTIVE:To investigate the molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of renal ischemia/reperfusion injury.METHODS:(1) Human umbilical cord mesenchymal stem cells were cultured and exosomes were obtained and identified using an exosome extraction kit.(2) The distribution of exosomes in the kidney of mice with renal ischemia/reperfusion injury was examined by intravital fluorescence imaging.(3) Thirty C57/BL6 male mice were divided into five groups according to the random number table method:sham operation group,renal ischemia/reperfusion group,sham operation group+Compound C group,renal ischemia/reperfusion+exosome group (exosome group),and renal ischemia/reperfusion+exosome+Compound C group (exosome+Compound C group),with 6 mice in each group.Except the sham operation group,bilateral renal pedicles were clamped for 45 minutes and a mouse model of renal ischemia/reperfusion injury was established after 24 hours of reperfusion.In sham operation+Compound C group and exosome+Compound C group,AMPK inhibitor Compound C was intraperitoneally injected 30 minutes before model establishment.In the exosome group and exosome+Copmpound C group,exosomes were injected through the tail vein 15 minutes before renal pedicle clipping.The levels of serum creatinine and urea nitrogen,interleukin 6,and tumor necrosis factor α in renal tissue,and the expression of apoptosis-related factors in renal tissue were detected after 24 hours of reperfusion in each group.RESULTS AND CONCLUSION:(1) Human umbilical cord mesenchymal stem cell exosomes had the typical tea tray morphology,with the diameter distribution in the range of 40-160 nm,and expressed the specific marker membrane protein of exosome surface.(2) Murine kidneys after renal ischemia/reperfusion injury were more likely to gather human umbilical cord mesenchymal stem cell exosomes compared with the sham operation group.(3) Exosome pretreatment reduced renal injury and the level of renal cell apoptosis in mice treated with renal ischemia/reperfusion injury.Moreover,this protective effect could be reversed by AMPK inhibitors.These findings verify that human umbilical cord mesenchymal stem cell-derived exosomes exerting a protective effect on renal ischemia/reperfusion injury may be related to the activation of the AMPK/YAP1 pathway to antiapoptosis.

Objective:To investigate the occurrence and influencing factors of oral frailty among the elderly in China.Methods:General information questionnaire,Oral Frailty Scale,Sarcopenia Screening Questionnaire(SARC-F),Social Network Scale-6(LSNS-6)and Subjective Cognitive Decline Questionnaire(SCD-Q9)were used to conduct a survey in Anhui Province.A survey was conducted among 3 063 elderly people to analyze their current status and influencing factors related to oral frailty.Results:The incidence of oral frailty among the elderly in Anhui Province was 46.82％(1434/3063).Binary logistic regression analysis showed sarcopenia(OR=8.742,95％CI:7.156-10.679),social isolation(OR=1.601,95％CI:1.313-1.953),and subjective cogni-tive decline(OR=2.424,95％CI:1.905-3.085),90 years old and above(OR=2.261,95％CI:1.304-3.922)and having disability(OR=1.341,95％CI:1.040～1.729)are risk factors for oral frailty in the elderly in Anhui Province.Conclusion:The incidence of oral frailty is high among the elderly in Anhui Province.Risk factors for oral frailty include sarcopenia,social isolation,subjective cognitive decline,advanced age,and disability.