OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

ObjectiveAngelicae Sinensis Radix， a commonly used medicinal herb with both medicinal and edible properties， is frequently adulterated in the market， severely affecting the clinical efficacy of preparations. While qualitative identification techniques for adulterants and counterfeits are now relatively mature， quantitative detection methods for adulterated processed products remain unexplored. Quantitative detection research of Angelicae Sinensis Radix and its primary closely related adulterant， "Tu Danggui" （Angelica gigas）， was conducted to establish a herbal quantitative molecular detection （Herb-Q） method for Angelicae Sinensis Radix and its processed products， providing a model for the establishment of quantitative detection technologies for Angelicae Sinensis Radix and related health products. MethodsThe specific single-nucleotide polymorphism （SNP） loci of Angelicae Sinensis Radix and Angelica gigas Nakai were screened based on the complete chloroplast genome sequence. The specific SNP loci of Angelicae Sinensis Radix were selected for quantitative methodological investigations （linearity， limit of quantification， limit of detection， and reproducibility） by mixing the powder of the herbs with different adulteration ratios. Huoxue Zhitong powder with three distinct adulteration ratios （15%， 25%， and 35%） was utilized to ascertain the precision of the Herb-Q method for the quantitative detection of Chinese patent medicines containing Angelicae Sinensis Radix. ResultsBy comparing the 123 chloroplast genome sequences of Angelicae Sinensis Radix， based on the principles of intraspecies conservation， interspecies specificity， and meeting the requirements of pyrophosphate high-throughput sequencing， it was determined that 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 and 38 592^nd locus （T/C） in the chloroplast genome sequence NC_029393.1 could be the exclusive molecular identification loci of Angelicae Sinensis Radix and Angelica gigas Nakai， respectively. The linear relationship R² of the Herb-Q method established by selecting the specific 9 674^th locus （A/G） of Angelicae Sinensis Radix was 0.997 4 （R²>0.99）， indicating an excellent linear relationship. The limits of quantification and detection were established at 2.0%， exhibiting excellent reproducibility ［relative standard deviation（RSD）<2.0%］. The established quantitative system based on the Herb-Q method detected the adulteration amount of counterfeit A. gigas in the Huoxue Zhitong powder， with an average deviation of 1.3% for three molecular quantitative replicates. ConclusionThis research demonstrates that the Herb-Q quantitative detection method established based on the 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 of Angelicae Sinensis Radix has good applicability， objectivity， and accuracy for Angelicae Sinensis Radix and A. gigas， and its processed products. This method has the capacity to provide technical support for the quantitative detection of commercially available Angelicae Sinensis Radix derivatives， including traditional Chinese medicinal preparations， dietary supplements， and nutraceuticals.

ObjectiveAngelicae Sinensis Radix， a commonly used medicinal herb with both medicinal and edible properties， is frequently adulterated in the market， severely affecting the clinical efficacy of preparations. While qualitative identification techniques for adulterants and counterfeits are now relatively mature， quantitative detection methods for adulterated processed products remain unexplored. Quantitative detection research of Angelicae Sinensis Radix and its primary closely related adulterant， "Tu Danggui" （Angelica gigas）， was conducted to establish a herbal quantitative molecular detection （Herb-Q） method for Angelicae Sinensis Radix and its processed products， providing a model for the establishment of quantitative detection technologies for Angelicae Sinensis Radix and related health products. MethodsThe specific single-nucleotide polymorphism （SNP） loci of Angelicae Sinensis Radix and Angelica gigas Nakai were screened based on the complete chloroplast genome sequence. The specific SNP loci of Angelicae Sinensis Radix were selected for quantitative methodological investigations （linearity， limit of quantification， limit of detection， and reproducibility） by mixing the powder of the herbs with different adulteration ratios. Huoxue Zhitong powder with three distinct adulteration ratios （15%， 25%， and 35%） was utilized to ascertain the precision of the Herb-Q method for the quantitative detection of Chinese patent medicines containing Angelicae Sinensis Radix. ResultsBy comparing the 123 chloroplast genome sequences of Angelicae Sinensis Radix， based on the principles of intraspecies conservation， interspecies specificity， and meeting the requirements of pyrophosphate high-throughput sequencing， it was determined that 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 and 38 592^nd locus （T/C） in the chloroplast genome sequence NC_029393.1 could be the exclusive molecular identification loci of Angelicae Sinensis Radix and Angelica gigas Nakai， respectively. The linear relationship R² of the Herb-Q method established by selecting the specific 9 674^th locus （A/G） of Angelicae Sinensis Radix was 0.997 4 （R²>0.99）， indicating an excellent linear relationship. The limits of quantification and detection were established at 2.0%， exhibiting excellent reproducibility ［relative standard deviation（RSD）<2.0%］. The established quantitative system based on the Herb-Q method detected the adulteration amount of counterfeit A. gigas in the Huoxue Zhitong powder， with an average deviation of 1.3% for three molecular quantitative replicates. ConclusionThis research demonstrates that the Herb-Q quantitative detection method established based on the 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 of Angelicae Sinensis Radix has good applicability， objectivity， and accuracy for Angelicae Sinensis Radix and A. gigas， and its processed products. This method has the capacity to provide technical support for the quantitative detection of commercially available Angelicae Sinensis Radix derivatives， including traditional Chinese medicinal preparations， dietary supplements， and nutraceuticals.

To improve the targeted therapeutic effect of magnolol (Mag) on neuroblastoma, Mag-loaded mitochondria-targeting immunoliposomes modified by datuximab (aGD2) and triphenylphosphine (TPP) (Mag/aGD2-T-ILN) were prepared, and their physicochemical properties, targeting characteristics and anti-tumor activity were evaluated. Physico-chemical properties showed that the surface of Mag/aGD2-T-ILN was smooth and spherical, with good dispersibility. The particle sizes, PDI and Zeta potentials of Mag/aGD2-T-ILN were measured to be (136.5 ± 5.1) nm, 0.184 ± 0.010 and (27.5 ± 3.6) mV, respectively. Mag/aGD2-T-ILN could release the drug continuously and slowly, and maintain good stability at 4 ℃. Cytotoxicity test exhibited that the IC50 of 2-ME/aGD2-T-ILN was (4.07 ± 0.48) µmol/L, and compared with free Mag, the toxicity of Mag/aGD2-T-ILN to SH-SY5Y cells increased by 6.4 times. Cellular binding and uptake assays suggested that Rho-aGD2-T-ILN could specifically target GD2-positive tumor cells and then further reach their mitochondria. Therapeutic efficacy indicated that Mag/aGD2-T-ILN could better suppress the growth of SH-SY5Y tumor cells in the body with lower toxicity and less side-effects. The results demonstrated that the Mag/aGD2-T-ILN nanoparticles system could achieve intracellular endocytosis through specific binding of antibodies and antigens between the carrier and the surface of tumor cells and electrostatic interaction, then effectively delivered and released the drugs into mitochondria by crossing the mitochondrial phospholipid membrane through TPP, and thus achieving mitochondria-targeting therapy of Mag/aGD2-T-ILN. Through the construction of this active targeting delivery system, the clinical application value of datuximab and Mag is improved, providing a novel approach for the clinical treatment of neuroblastoma.

Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

Objective To investigate the mechanism by which Guijianyu ameliorates podocyte injury in a mouse model of diabetic kidney disease(DKD)induced by advanced glycation endproducts(AGEs).Methods Sixty db/db mouse models of DKD were randomized equally into 5 groups for treatment with saline,Guijianyu extract at 3 doses or irbesartan for 12 weeks,and the changes in renal pathology and structure were observed using transmission electron microscopy,and the expressions of related genes and key proteins were detected using RT-qPCR and immunohistochemistry.In cultured MPC-5 cells incubated with 50 mg/L AGEs-BSA for 24 h,the effect of different concentrations of Guijianyu extract on cell viability was examined with CCK-8 assay;Western blotting was performed to detect the protein expressions of RAGE,VEGFA,TNF-α,NF-κB(p65),IL-6 and caspase-3,and the mRNA expressions of RAGE,NF-κB(p65),VEGFA and IL-6 were detected with RT-qPCR.Results In mouse models of DKD,treatment with high-dose Guijianyu extract significantly reduced renal expressions of RAGE,VEGFA,NF-κB(p65),and IL-6 proteins and the mRNA expressions of RAGE,NF-κB,and IL-6.In MPC-5 cells,exposure to AGEs significantly reduced cell viability and increased the protein expressions of RAGE,NF-κB(p65),VEGFA,TNF-α,IL-6 and caspase-3(P<0.05)and mRNA expressions of RAGE,NF-κB(p65),VEGFA,and IL-6.Treatment with Guijianyu extract obviously improved cell viability and reduced the expressions of RAGE,NF-κB(p65),VEGFA,TNF-α,IL-6,and caspase-3.Furthermore,Guijianyu extract effectively reversed RAGE agonist-induced elevation of protein expressions of RAGE,VEGFA,TNF-α,IL-6,and caspase-3 and mRNA expressions of RAGE,NF-κB(p65),IL-6,and VEGFA in MPC-5 cells.Conclusion Guijianyu extract ameliorates AGEs-induced mouse renal podocyte injury in DKD by inhibiting the activation of AGEs-RAGE signaling pathway and reducing the expressions of pro-inflammatory cytokines and vascular endothelial growth factors.

Objective:To summarize the initial experience of 5G-ultra-long-distance robotic hepatectomy.Methods:This is a retrospective case series study. The clinical information from 5 cases of 5G ultra-long-distance robot-assisted hepatectomy performed was collected from June 2023 to October 2024, in collaboration between Sir Run Run Shaw Hospital, Zhejiang University School of Medicine in Hangzhou and Alaer Hospital, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine in Alaer, located 4 600 km apart. The patients comprised 1 male and 4 females, aged from 36 to 59 years, with an average age of 48 years. Their body mass index ranged from 20.4 to 30.9 kg/m2, with an average of 24.62 kg/m2. Preoperatively, 5 patients were diagnosed with liver disease requiring hepatectomy. The operations used 5G ultra-remote four-arm endoscopic robot surgery system. The remote control room was located in Sir Run Run Shaw Hospital (Hangzhou, Zhejiang), and the robot operating room was located in Alaer Hospital (Alaer, Xinjiang). The wired network relied on 60 Mb/s high-speed public Internet special line (China Telecom). In order to ensure the security of data transmission, the system implemented a double-layer encryption strategy for the wired network, and carried out strict debugging and verification for both the wired and wireless networks. Perioperative data and information on network performance were collected for 5 patients.Results:The surgical duration of the 5 cases of 5G ultra-long-distance robot-assisted hepatectomy ranged from 49 to 342 minutes, with an average of 184 minutes. Intraoperative blood loss varied from 5 to 800 ml, averaging 183 ml. Network performance was evaluated during the surgery, revealing an average network latency of 108.2 ms, with no significant lag or delay observed during any of the procedures. All patients recovered smoothly, with a postoperative hospital stay ranging from 5 to 10 days, averaging 7.2 days. Postoperative complications included 1 case of hypoproteinemia and 1 case of pleural effusion. Pathological examination confirmed that all cases suffered benign liver diseases (three patients with hepatic hemangioma, one with regenerative nodule in cirrhosis, and one with hepatolithiasis and choledocholithiasis).Conclusion:The preliminary exploration of clinical practice indicated that 5G-ultra-long-distance robot-assisted surgery is feasible for hepatectomy, with no severe complications affecting patients′ recovery.

This study aims to investigate the effect of Lactiplantibacillus plantarum LP12 on obe-sity prevention.In our study,Lactiplantibacillus plantarum LP12 was added to the diet for feed-ing,and the blood biochemistry status of rabbit,as well as the antioxidant effect of serum and liver samples were analyzed by determining the body weight change and feed intake of Japanese White rabbits.The changes in colony structure and abundance were also analyzed by 16S rDNA sequen-cing.The results showed that supplementation of Lactiplantibacillus plantarum LP12 inhibits weight gain,decreases serum glucose and ALT levels,and increases SOD activity in the liver.16S RNA gene sequencing analysis showed that the addition of Lactiplantibacillus plantarum LP12 increases the abundance of Bacteroidetes and Desulfovibrioides at the phylum level,and the supple-mentation of Lactiplantibacillus plantarum LP12 increases the abundance of Muribaculaceae at the genus level.Predictive analysis of microbiota function revealed that the supplementation of Lactiplantibacillus plantarum LP12 positively regulated iron-sulfur clusters and Zn-dependent proteases.In conclusion,the addition of Lactiplantibacillus plantarum effectively inhibits weight gain in Japanese White rabbits,enhances the antioxidative activity of the liver,and induces altera-tions in the gut microbiota composition of these rabbits.These findings lay an experimental foun-dation for further exploring the mechanisms by which Lactobacillus plantarum LP12 exerts its preventive effects against obesity and promotes metabolic health.