It has been popular and challenging to undertake researches on the delay of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). As key cells for tumor initiation, cancer stem cells (CSC) play an important role in the process of resistance to EGFR-TKI. Although preliminary studies found that traditional Chinese medicine (TCM) could inhibit CSC properties and delay EGFR-TKI resistance, the specific molecular mechanism remains unclear. By summarizing the empirical syndrome treatment of EGFR-TKI resistance via TCM and combining recent researches on TCM intervention in CSC to delay EGFR-TKI resistance, this review discussed the potential molecular pathways and mechanisms of deceleration in resistance to EGFR-TKI by TCM via inhibiting CSC characteristics, in order to expand the research ideas of TCM in combination with targeted therapy.
Humans ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Medicine, Chinese Traditional ; Neoplasms/drug therapy* ; Animals ; Drugs, Chinese Herbal/therapeutic use*

Hepatitis B virus (HBV) infection represents a significant global health challenge. Current therapeutic options, such as interferon and nucleoside analogues (NAs), are limited by issues including long-term medication toxicity, the virus's propensity to develop drug resistance, and the inability to eradicate covalently closed circular DNA (cccDNA). Core protein allosteric modulators (CpAMs), as an emerging class of anti-HBV drugs, target HBcAg to interfere with capsid assembly. This not only blocks viral nucleocapsid formation and inhibits viral replication but also indirectly destabilizes the cccDNA pool, while exhibiting a relatively high genetic barrier to resistance. This article systematically evaluates HBV drug resistance to CpAMs and proposes anti-resistance strategies, including the combination of nucleoside analogues with CpAMs, enhancing protein-drug interactions, targeting HBcAg degradation, designing multi-target inhibitors, and employing combination therapy. Looking ahead, the integration of structural biology, computational chemistry, and immunotherapy will offer innovative approaches for developing novel, highly effective, and low-resistance inhibitors, thereby advancing the functional cure of hepatitis B.

AIM:To evaluate the value of ultra-sound-guided erector spinae plane block(ESPB)combined with opioid-sparing anaesthesia in extra-corporeal shock wave lithotripsy(ESWL)for pancre-atic stones.METHODS:A total of 96 patients(60 males and 36 females,aged 20-65 years,ASA Ⅰ-Ⅱ,BMI 16-30 kg/m2)undergoing elective extracorpo-real shock wave lithotripsy for pancreatic duct stones were selected in our hospital from March 2022 to April 2023.The patients were randomly di-vided into conventional intravenous anesthesia group(group C,48 cases)and ESPB+opioid-sparing group(group E,48 cases).Patients in group C un-derwent general anesthesia with target-controlled infusion of propofol and remifentanil with sponta-neous breathing.Patients in group E underwent ul-trasound-guided bilateral ESPB before intravenous general anesthesia.The changes of hemodynamic indexes(HR,MAP)in the two groups were ob-served and recorded.The anesthetic effect,dosage of remifentanil,quality of anesthesia recovery,postoperative analgesic effect and incidence of perioperative adverse reactions(respiratory depres-sion,nausea and vomiting,pruritus,etc.)were ob-served in the two groups.RESULTS:Compared with group C,the incidence of intraoperative respiratory depression was significantly decreased,the intraop-erative consumption of remifentanil was de-creased,and the postoperative recovery time was shortened in group E(P＜0.05).The VAS scores of rest and cough pain and the incidence of postoper-ative nausea and vomiting were significantly de-creased in group E(P＜0.05).There was no signifi-cant difference in HR and MAP between the two groups(P＞0.05).CONCLUSION:Ultrasound-guided ESPB in ESWL for pancreatic duct stones is satisfac-tory and can save opioids with few complications.

AIM:To evaluate the value of ultra-sound-guided erector spinae plane block(ESPB)combined with opioid-sparing anaesthesia in extra-corporeal shock wave lithotripsy(ESWL)for pancre-atic stones.METHODS:A total of 96 patients(60 males and 36 females,aged 20-65 years,ASA Ⅰ-Ⅱ,BMI 16-30 kg/m2)undergoing elective extracorpo-real shock wave lithotripsy for pancreatic duct stones were selected in our hospital from March 2022 to April 2023.The patients were randomly di-vided into conventional intravenous anesthesia group(group C,48 cases)and ESPB+opioid-sparing group(group E,48 cases).Patients in group C un-derwent general anesthesia with target-controlled infusion of propofol and remifentanil with sponta-neous breathing.Patients in group E underwent ul-trasound-guided bilateral ESPB before intravenous general anesthesia.The changes of hemodynamic indexes(HR,MAP)in the two groups were ob-served and recorded.The anesthetic effect,dosage of remifentanil,quality of anesthesia recovery,postoperative analgesic effect and incidence of perioperative adverse reactions(respiratory depres-sion,nausea and vomiting,pruritus,etc.)were ob-served in the two groups.RESULTS:Compared with group C,the incidence of intraoperative respiratory depression was significantly decreased,the intraop-erative consumption of remifentanil was de-creased,and the postoperative recovery time was shortened in group E(P＜0.05).The VAS scores of rest and cough pain and the incidence of postoper-ative nausea and vomiting were significantly de-creased in group E(P＜0.05).There was no signifi-cant difference in HR and MAP between the two groups(P＞0.05).CONCLUSION:Ultrasound-guided ESPB in ESWL for pancreatic duct stones is satisfac-tory and can save opioids with few complications.

Objective To observe the effects of acute normovolemic hemodilution(ANH)on target-controlled infusion(TCI)of etomidate blood drug concentration and adrenal cortical function.Methods Sixty patients who undergo elective multisegmental spine surgery,35 males and 25 females,aged 30-60 years,BMI 20-25 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups using random number table method:ANH group and control group,30 patients in each group.Both groups used a target-controlled infusion of etomidate for anesthesia induction and anesthesia maintenance.In the ANH group,ANH was performed after steady anesthesia induction,ideal Hct 28％to 30％,and transfused within 1 hour after surgery;the control group was routinely treated.The dosage of etomidate was recorded.Liquid chroma-tography-tandem mass spectrometry(LC-MS/MS)was used to detect etomidate blood concentrations at the immediate postoperative,10,20,and 30 minutes postoperative periods in the two groups,and the immedi-ate moment autologous blood collected into the storage bag,preserved in the storage bag for 1 hour,and the immediate moment transfused back in the ANH group.Plasma concentrations of cortisol(Cor),adrenocorti-cotropic hormone(ACTH),and aldosterone(ALD)were measured by chemiluminescence immunoassay(CLIA)before the induction of anesthesia,immediately after the operation,and at 1 day and 2 days postop-eratively.Results There was no significant difference in the total dosage of etomidate between the two groups.Compared with the immediate postoperative period,the plasma etomidate concentration was signifi-cantly decreased 10,20,and 30 minutes after surgery(P<0.05).Compared with the control group,the concentration increased significantly 10 minutes after surgery in the ANH group(P<0.05).The plasma concentrations of etomidate were(547.8±119.4)ng/ml at the immediate moment autologous blood collected into the storage bag,(536.7±107.8)ng/ml at the preserved in the storage bag for 1 hour,and(522.8±91.7)ng/ml at theimmediatemoment transfusedbackinthe ANHgroup.Comparedwithbeforein-duction of anesthesia,the concentration of Cor and ALD immediately after the operation decreased signifi-cantly(P<0.05)and the concentration of ACTH was significantly higher(P<0.05).There were no sta-tistically significant differences in the concentrations of Cor,ALD,and ACTH between the two groups before induction of anesthesia 1 day and 2 days postoperatively.Conclusion In the orthopedic surgery of TCI eto-midate,return transfusion of collected autologous blood transiently(about 10 minutes)increases etomidate blood concentrations,the function of adrenal cortical will recover to the preoperative level within 24 hours after the operation.

Diabetic nephropathy(DN)is a common complication of diabetes and a leading cause of end-stage renal disease.Transforming growth factor-β1(TGF-β1)/SMAD signaling activation plays an important role in the onset and progression of DN.Reported findings suggest that the activation of TGF-β1(including the latent form,the active form,and the receptors)and its downstream signaling proteins(SMAD3,SMAD7,etc.)plays a critical role in DN.In addition,TGF-β1/SMAD signaling may mediate the pathogenesis and progression of DN via various microRNAs(miRNAs)and long non-coding RNAs(lncRNAs).Emerging evidence shows that TGF-β1,SMAD3,and SMAD7 are the main signaling proteins that contribute to the development of DN,and that they can be potential targets for the treatment of DN.However,recent clinical trials have shown that the anti-TGF-β1 monoclonal antibody treatment fails to effectively alleviate DN,which suggests that upstream inhibition of TGF-β1/SMAD signaling does not alleviate clinical symptoms and that this may be related to the fact that TGF-β1/SMAD has multiple biological effects.Targeted inhibition of the downstream TGF-β1 signaling(e.g.,SMAD3 and SMAD7)may be an effective approach to attenuate DN.This article discussed the current understanding of the molecular mechanisms and potential targets for the treatment and prevention of DN by focusing on TGF-β1/SMAD signaling.

Objective To study the significance of leptin and its receptor(OB-R) in the occurrence and development of pulmonary arterial hypertension(PAH) induced by monocrotaline(MCT).Methods Fifteen SD rats were divided into the control group(n=5) and two experimental groups(n=10).The experimental groups were intraperitoneally injected by MCT for constructing the PAH model and the control group was injected by the same dose of solvent groups.The venous blood was extracted at 2,4 weeks after MCT injection in the two experimental groups.The mean pulmonary artery pressure(mPAP) and right ventricular hypertrophy index(RVHI) were measured and then the lung tissue was removed.The pathological change of lung blood vessels was observed.The expression of serum leptin was detected by ELISA.The expression of OB-R in lung tissue was tested by Western blot.Results Compared with the control group,mPAP and RVHI in the experimental groups were significantly increased(P＜0.05);the expression levels of serum leptin and lung tissue OB-R were increased significantly(P＜0.05),moreover,which were positively correlated with mPAP(r=0.912,P＜0.05;r=0.861,P＜0.05).Conclusion Leptin and OB-R may play an important role in the occurrence and development of PAH induced by MCT.

Objective To evaluate the change of clinicopathological features and prognosis of papillary thyroid cancer over a 15-year period.Methods The clinicopathological features and outcomes of papillary thyroid cancer patients were analyzed in three groups according to the time of diagnosis:group Ⅰ (1997-2001),group Ⅱ (2002-2006),and group Ⅲ (2007-2011).Results As time advanced,the average age of papillary thyroid cancer patients increased,tumor stage,like size,extrathyroid invasion and lymph node metastasis decreased dramatically (P ＜ 0.01).The percentage of multifocality and bilaterality increased.The long-term follow up data (median follow up time was 6.6 years),indicated that the 15-year over all survival was 97.8％ and the 15-year disease-free survival was 90.2％.Tumor ≥3 cm,bilaterality,extrathyroid invasion,lymph node metastasis and AJCC stage were correlated with tumor recurrence.By multivariate COX-regression analysis only lymph node metastasis and bilaterality were independent risk factors.Conclusion The clinicopathological features of papillary thyroid cancer changed over 15 years,with the percentage of early-staged patients increased.Lymph node metastasis and bilaterality are two risk factors for tumor recurrence.

Objective To analyze the characteristics of left ventricular systolic function in Kawasaki disease (KD) patients with intravenous immunoglobulin (IVIG) resistant during acute phase by two-dimensional speckle tracking imaging (2D STI).Methods IVIG resistant patients (n=40) as well as age and gender matched IVIG responder patients (n=40) were selected from KD patients in acute phase.Patients in IVIG resistant group were further divided into coronary artery dilation (CAD) subgroup and no coronary artery dilation (NCAD) subgroup.Then conventional echocardiography,2D STI and laboratory indexes were acquired and compared between IVIG resistant group and IVIG responder group,as well as between CAD and NCAD subgroup.ROC curve analysis was used to determine threshold values of 2D STI measurements associated with IVIG resistance.Results Compared with IVIG responder group,coronary artery dilation,left ventricular mass and left ventricular mass index increased,systolic global longitudinal strain (GLS) and systolic global circumferential strain (GCS) decreased,albumin,erythrocyte sedimentation rate,C-reactive protein and platelet increased in IVIG resistant group (all P＜0.05).Taking absolute GLS 16.8％ as a threshold,the area under curve (AUC) was 0.769 (P=0.021),sensitivity,specificity in diagnosis of IVIG resistant was 79.27％,68.36％.Taking absolute GCS 15.9％ as a threshold,AUC was 0.749 (P=0.038),sensitivity,specificity in diagnosis of IVIG resistant was 71.43％,57.28％.Conclusion IVIG resistant KD patients present significantly greater systolic dysfunction compared with responders in patients with KD,which may be the results of myocardium infection other than coronary artery lesions.2D STI may predict myocardial injury in IVIG resistant KD patients.

Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.
Angiotensin II* ; Angiotensins* ; Animals ; Arteries ; Atherosclerosis* ; Cell Proliferation ; Focal Adhesion Protein-Tyrosine Kinases ; Gene Expression ; In Vitro Techniques ; Macrophages ; Mice* ; Muscle Development ; Muscle, Smooth, Vascular ; NF-kappa B ; Plaque, Atherosclerotic ; RNA, Small Interfering ; Signal Transduction ; Sirolimus