Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） combined with neoadjuvant chemotherapy in the treatment of early triple-negative breast cancer （TNBC）. METHODS Randomized controlled trials （RCTs） comparing ICIs combined with neoadjuvant chemotherapy （experimental group） versus neoadjuvant chemotherapy alone （control group） were retrieved from PubMed， Cochrane Library， Embase， Web of Science， CNKI， Wanfang Data， and VIP databases， as well as relevant studies published at oncology academic conferences. The search period was from database inception to June 30， 2025. After literature screening， data extraction， and quality assessment， a meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 6 RCTs involving 3 786 patients were finally included. The meta-analysis results showed that the experimental group had superior event-free survival [HR＝0.73， 95%CI （0.62， 0.85）， P＜0.000 1]， overall survival [HR＝0.69， 95%CI （0.57， 0.84）， P＝0.000 3]， and pathological complete response （pCR） [OR＝1.57， 95%CI （1.37， 1.80）， P＜0.000 01] compared to the control group. The incidence of ≥grade 3 adverse event （AE）， severe AE （SAE）， and ≥ grade 3 immune-related adverse event （irAE） in the experimental group was significantly higher than that in the control group. There was no statistically significant difference between the two groups in the incidence of any AE or any irAE （P＞0.05）. Subgroup analysis revealed that， regardless of programmed cell death ligand 1 expression status （negative or positive），the pCR in the experimental group was significantly higher than that in the control group （P＜0.05）. Additionally， the pCR of the patients with positive lymph nodes in the experimental group was significantly higher to that in the ontrol group （P＜0.05）. There was no statistically significant difference in pCR between the two groups with negative lymph nodes （P＝0.09）. CONCLUSIONS ICIs combined with neoadjuvant chemotherapy can significantly improve event-free survival and overall survival in patients with TNBC， providing patients with long-term survival benefits. However， the risk of ≥ grade 3 AE， SAE and ≥ grade 3 irAE has increased.

Transferrin receptor 1(TfR1), a key membrane protein regulating cellular iron uptake, is extensively involved in physiological processes such as cell proliferation, metabolism, and immune responses. In recent years, advancements in understanding the structure, function, and dysregulated expression mechanisms of TfR1 in diseases have revealed its potential as a therapeutic target in a wide range of pathologies, including cancer, neurodegenerative disorders, and muscular dystrophies. The high expression of TfR1 in numerous tumor types makes it an attractive target for anticancer drug delivery systems. In neurological conditions such as AD, TfR1-mediated transcytosis across the blood-brain barrier(BBB) offers a promising strategy for brain-targeted delivery of biologics such as antibodies and oligonucleotides. For muscular dystrophy treatment, TfR1-targeted antibody-oligonucleotide conjugates(AOCs) have considerably enhanced the tissue specificity and therapeutic efficacy of exon-skipping therapies. Concurrently, the role of TfR1 in cardiac iron metabolism has drawn attention to its potential applications in cardiovascular disease intervention. In this paper, the molecular mechanisms of TfR1 and the research progress of targeted therapy in various diseases are reviewed, focusing on the recent advances in cutting-edge technologies such as drug delivery system, antibody engineering and AOC platform based on TfR1, and discussing the challenges and prospects in clinical transformation, in order to provide new ideas for the precise application and clinical transformation of therapeutic strategies targeting TfR1 in various diseases.

The principle of "supplementing or draining by the preference and aversions of the the five zang organs" emphasizes that prescriptions should align the five flavors of medicinals with the needs of the five organs， achieving supplementation through harmonizing flavors and drainage through opposing flavors. This paper analyzed the formulas for regulating the spleen found in Wings of the Thousand Gold Pieces Formulary （《千金翼方》） from the perspective of "supplementing or draining by the preference and aversions"， to summarize SUN Simiao's prescription characteristics for treating spleen-related disorders. In terms of the combination rule of medicinal properties and flavors， formulas like Bupi Decoction （补脾汤） for supplementing the spleen use sweet and warm medicinals paired with bitter and drying medicinals； those for draining the spleen use acrid and warm medicinals paired with bitter and cold medicinals； those for warming the spleen employs acrid and hot medicinals with sweet and warm medicinals； those like Jianpi Decoction （建脾汤） for strengthening spleen combines sweet and warm with sour and bitter medicinals； Zhuanpi Pill （转脾丸） pairs acrid and warm medicinals with sweet and warm medicinals； and Roupi Decoction （柔脾汤） uses sweet and warm medicinals with sweet and bitter medicinals. Regarding the medicinal flavors， warm dominates the four qi （the four properties）， while sweet， bitter， and acrid are the main among the five flavors. Clinical practice involves applying comprehensive therapy methods such as the combination of sweet and bitter to harmonize， acrid and sweet to transform yang， pungent to disperse and bitter to descend， balancing cold and warm， and combining supplementation and drainage. The foundational principle is to tonify spleen qi and protect the middle jiao， and treatment is tailored based on the disease condition， location， nature， and the characteristics of the medicinals， with careful selection of suitable dosage forms and administration methods.

Objective To investigate the protective effect and mechanism of astragaloside Ⅳ(AS-Ⅳ)on the pulmonary arterial hypertension(PAH)model induced by monocrotaline(MCT)/monocrotaline pyrrole(MCTP)in SD rats/human pulmonary artery endothelial cell(HPAEC).Methods In vivo experiment,60 male SD rats were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(20 mg/kg)group,AS-Ⅳ medium-dose(40 mg/kg)group,AS-Ⅳ high-dose(80 mg/kg)group,or sildenafil(Sil,100 mg/kg)group,with 10 rats in each group;except for the control group,PAH rat models were established by single intraperitoneal injection of MCT(60 mg/kg)in other groups.In vitro experiment,HPAECs were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(10 μmol/L)group,AS-Ⅳ medium-dose(20 μmol/L)group,MCTP+AS-Ⅳ high-dose(40 μmnol/L)group,or p38 mitogen-activated protein kinase(MAPK)signaling pathway inhibitor(SB203580,5 μmol/L)group;except for the control group,in vitro PAH cell models were established by MCTP(60 μg/mL)induction for 24 h in other groups.In vivo experiments,after 4 weeks of drug intervention,the right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)of rats were measured by hemodynamic methods,the right ventricle hypertrophy index was measured by weighing methods,the percentage of pulmonary arteriole wall thickness to outer diameter(WT％)and percentage of the wall area to total vascular area(WA％)were observed by hematoxylin-eosin staining,the expression of cysteine aspartic acid specific protease 3(caspase 3)protein in lung tissue was observed by immunohistochemistry(IHC),and the apoptosis of lung tissue cells was detected by TUNEL assay.In vitro experiments,JC-1 staining was used to detect the mitochondrial membrane potential in cells,and immunofluorescence was used to detect caspase 3 protein expression.In vitro and in vivo experiments,Western blotting was used to detect the expression of caspase 3,B-cell lymphoma gene 2(Bcl-2),Bcl-2 associated X protein(Bax),p38 MAPK,and phosphorylated p38 MAPK proteins in lung tissue and HPAECs.Results In vivo experiments,the RVSP,mPAP,and right ventricle hypertrophy index were decreased in the Sil group and each dose group of AS-Ⅳ(all P＜0.01);the WA％and WT％of each dose group of AS-Ⅳ were decreased(all P＜0.01),the expression of caspase 3 protein in lung tissue was decreased(all P＜0.01),and the apoptosis of lung tissue cells was decreased(all P＜0.01).In vitro experiments showed that after intervention with each dose of AS-Ⅳ and SB203580,the mitochondrial membrane potential of HPAEC was increased(all P＜0.01)and the expression of caspase 3 was decreased(all P＜0.01).In vivo and in vitro experiments,each dose of AS-Ⅳand SB203580 reduced the expression of Bax and phosphorylated p38 MAPK proteins,and increased the expression of Bcl-2 protein(all P＜0.01).Conclusion AS-Ⅳ reduces apoptosis by inhibiting p38 MAPK signaling pathway,improving PAH in SD rats.

ObjectiveTo understand the distribution of enrofloxacin (ENR) residues in freshwater fish, to evaluate the dietary exposure risk to ENR for consumers through the consumption of different freshwater fish in Shanghai, and to provide a reference for controlling antibiotic residues in freshwater fish. MethodsGrass carp, Wuchang bream, pond loach, and Asian swamp eels were purchased from the markets in Shanghai. After being fed with ENR, the fish were divided into 42 batches according to their species and weight, and thereafter ENR residues in the muscles and skin of the fish were measured. In addition, a total of 44 batches of Wuchang bream, pond loach, Asian swamp eels were purchased from the markets, and the ENR residues in the muscles with or without the fish skin were measured, and the exposure risk was evaluated. ResultsThe average residues of ENR in skin of the freshwater fish after being fed with drugs in the 42 groups were higher than those in muscles (M=659.38 μg·kg^-1, M=460.83 μg·kg^-1; z=-2.212, P=0.027). The over-standard rates of ENR residues in the muscles with or without skin 44 batches of freshwater fish of sold in Shanghai were 36.36% and 29.55%, respectively. The median exposure, P₉₅ exposure, and maximum exposure to ENR through the consumption of the muscles with the skin for adults and children in Shanghai were higher than those through the consumption of muscles without the skin. For children, the margin of safety (MOS) for the max exposure to ENR by consuming the muscles with the skin was more than 1, while the MOS was less than 1 in all other cases for both children and adults. ConclusionThe ENR residues in the skin of freshwater fish are generally higher than those in the muscles. The risk of ENR residues in freshwater fish sold in Shanghai is within a controllable range. However, there might be a certain risk of acute exposure to ENR for children by consuming muscles with the skin of freshwater fish.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective To evaluate the efficacy,safety and cost-effectiveness of dorzagliatin in the treatment of type 2 diabetes mellitus using a rapid health technology assessment,and to provide medical evidence for clinical decision-making.Methods PubMed,Embase,Cochrane Library,CNKI,Wanfang Data,SinoMed and relevant health technology assessment(HTA)websites and databases were searched to collect systematic reviews/Meta-analysis,pharmacoeconomic literature and HTA reports of dorzagliatin in the treatment of type 2 diabetes from inception to July 20,2024.Two reviewers independently screened literature,extracted date and assessed quality.The results were qualitatively described and analyzed.Results A total of 6 studies were included,including 5 systematic reviews/Meta-analysis and a pharmacoeconomic study.In terms of efficacy compared with placebo,dorzagliatin significantly reduced glycated hemoglobin(HbA1c),fasting plasma glucose,2-hour postprandial blood glucose and insulin resistance index(P＜0.05),improved HbA1c compliance rate in terms of safety,dorzagliatin,and enhanced homeostasis model assessment-β(P＜0.05),significantly increased total cholesterol,triglyceride,body weight and body mass index(P＜0.05).In terms of safety,the total incidence of adverse reactions of dorzagliatin was slightly higher than that of the placebo group(P＜0.05).However,there was no significant difference in the incidence of severe adverse reactions between the two groups(P＞0.05),and there was no significant increase in the incidence of hyperlipidemia and hypoglycemia(P＞0.05).In terms of economy,the treatment of dorzagliatin combined with metformin has a long-term cost-utility advantage,with an economic probability of nearly 70％.Conclusion Compared with placebo,dorzagliatin has a good overall efficacy and safety in the treatment of type 2 diabetes.In terms of safety,the total incidence of adverse reactions of dorzagliatin was slightly higher than that of placebo.In terms of economy,compared with metformin alone,dorzagliatin combined with metformin has economic advantages.However,there is a lack of head-to-head comparisons of doxorubicin with other classes of glucose-lowering medications,and none of the included studies described long-term cardiac,cerebral,or renal benefits,which limits the comprehensive evaluation of the efficacy and safety of dorzagliatin.

Objective To screen and identify significant influencing factors associated with voriconazole clearance using machine learning algorithms.Methods This study utilized a clinical dataset of elderly patients undergoing voriconazole treatment at our institution.We employed seven feature selection techniques from three categories of methods(filter,wrapper methodsand Embedded methods)to identify crucial influencing factors related to voriconazole clearance.Then six algorithms including Stochastic Gradient Descent Regression(SGDR),Lasso Regression(LassoR),Ridge Regression(RidgeR),Random Forest Regression(RFR),XGBoost Regression(XGBR),and Support Vector Regression(SVR),were applied to identify the best models by 5 fold cross-validation and the mean absolute error.SHAP values were employed to analyze the importance of influencing factors.Results The SVR model outperformed other regressors and were considered.The model was developed for seven selected features,which demonstrated good precision with an average relative error was 32.57%,and with approximately 57.89%of predicted values falling within a relative error range of±20%.The SHAP results revealed the importance ranking of influencing factors as ALT,ALP,PLT,administration method,CREA,TBIL,and PCT.Conclusion Feature selection techniques applied in machine learning can be utilized for the screening of influencing factors linked to voriconazole clearance.

Objective Based on the propensity score matching(PSM),the effect of flexible ureteroscopy combined with flexible negative pressure suction sheath in the treatment of infectious renal calculus lithotomy was analyzed.Methods From April 2022 to April 2024,87 patients with infectious renal calculus in our hospital were selected retrospectively.All patients were treated with flexible ureteroscopic lithotripsy(FURL).According to the different choice of ureteral access sheath(UAS)during operation,they were divided into negative pressure sheath group(n=43)and conventional sheath group(n=44).In the negative pressure sheath group,the flexible negative pressure suction sheath was used for FURL,and in the conventional sheath group,the conventional sheath was used for FURL.The general data of patients with infectious renal calculus between groups were compared,and the indicators were balanced by PSM.The clinical efficacy,perioperative indicators,levels of procalcitonin(PCT)and white blood cell count(WBC)and postoperative complications of patients with infectious renal calculus were compared between the two groups.Results After 1∶1 ratio matching by PSM,42 pairs of patients with infectious renal calculus were obtained,.The stone clearance rate of negative pressure sheath group[90.48%(38/42)]was significantly higher than that of conventional sheath group[71.43%(30/42)](P<0.05).The minimum intrapelvic pressure,average intrapelvic pressure and maximum intrapelvic pressure in the negative pressure sheath group were lower than those in the conventional sheath group,operation time and hospitalization time in the negative pressure sheath group were shorter than those in the conventional sheath group(P<0.05).The levels of PCT and WBC in the negative pressure sheath group were lower than those in the conventional sheath group at 2 h after operation,and the time for PCT and WBC to recover to the normal level were shorter than those in the conventional sheath group(P<0.05).The total incidence of postoperative complications in negative pressure sheath group[9.52%(4/42)]was significantly lower than that in conventional sheath group[28.57%(12/42)](P<0.05).Conclusion Flexible ureteroscopy combined with flexible negative pressure suction sheath is effective in the treatment of renal calculus,which is helpful to reduce intra-operative renal pelvis pressure,shorten operation time,reduce PCT and WBC levels after operation,and promote patients'early recovery with good safety.