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.

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.

Objective To study the effects of different implantation angles of bi-leaflet mechanical heart valve(BMHV)on swirling flow in the aorta.Methods Based on the aortic CT images of a healthy volunteer,the effects of 4 different valve implantation angles(0°,45°,90° and 135°)on the aortic swirling flow under constant flow conditions were studied by computational simulation.Results The implantation of BMHV could seriously interfere with the aortic swirling flow,affecting the structure and helicity distributions of the swirling flow in ascending aorta,thus resulting in disturbed blood flows distal to the valve.The 135° implantation angle caused the most disruption to the swirling flow,leading to the largest areas of reversed swirling flows,while the 0° and 45° implantation angles caused relatively smaller damage to the swirling flow.The areas with low wall shear stress(<0.5 Pa)were the smallest when the implantation angle of BMHV was 0°.Conclusions At the implantation angle of 0°-45°,the disruption of BMHV to the swirling flow in ascending aorta was relatively small.Therefore,for different patients,the selection of implantation angle should be individualized according to the spatial geometry of their aorta(including the aortic sinuses),and the implantation angle can be determined between 0°-45°.

Objective:To investigate the value of prostate biopsy guided by transrectal real-time ultrasonic elastography (TRTE) combined with peak strain index (PSI) in the diagnosis of prostate cancer and the correlation with TRTE score and pathological Gleason score.Methods:A total of 80 patients with suspected prostate cancer who underwent TRTE in the First Affiliated Hospital of Hebei North University from January 2019 to December 2019 were selected. The PSI for suspicious lesions was measured, and targeted puncture biopsy guided by TRTE combined with PSI was performed on the patients, and then followed by systematic puncture biopsy. The outcomes of targeted biopsy and systematic biopsy were analyzed. Taking pathological biopsy results as the gold standard, the detection rates of prostate cancer and benign prostate lesions detected by both biopsies methods were compared; the prostate volume, serum prostate specific antigen (PSA) level and PSI were compared between patients with prostate cancer and benign prostatic lesions. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to determine the best cut-off value of PSI in the diagnosis of prostate cancer. The values of conventional ultrasound versus TRTE combined with PSI in the diagnosis of prostate cancer were assessed. The positive rate of biopsy puncture points under the guidance of TRTE combined with PSI was compared with that of systematic biopsy. The correlation between TRTE score and pathological Gleason score of prostate malignant lesions was analyzed.Results:Among 80 patients, 45 patients (56.25%) were diagnosed as prostate cancer by prostate puncture biopsy, and 35 patients (43.75%) were benign prostate lesions. Among 45 patients with prostate cancer, 42 cases (93.33%) of prostate cancer were detected by using TRTE combined with PSI-guided targeted puncture biopsy, and 38 cases (84.44%) of prostate cancer were detected by using systematic puncture biopsy; there was no significant difference in the detection rate of prostate cancer by both biopsies methods ( χ2 = 1.80, P = 0.180). The level of serum PSA and PSI value in the prostate cancer group were higher than those in the benign prostate lesion group, and the difference was statistically significant ( t value was 65.28 and 14.93, all P < 0.05). The clinical value of PSI value in the diagnosis of prostate cancer was analyzed by using ROC curve. The results showed that the AUC was 0.857 (95% CI 0.772-0.941), and the optimal cut-off value of PSI was 5.68; PSI ≥ 5.68 was treated as the malignant cancer and PSI < 5.68 was treated as the benign cancer. The sensitivity, specificity and accuracy of TRTE combined with PSI in the diagnosis of prostate cancer were 91.11%, 94.29%, and 92.50%, respectively, which were higher than those of conventional ultrasound (73.33%, 68.57% and 71.25%), and the differences were statistically significant (all P < 0.05). A total of 89 suspected lesions were detected in 80 patients through TRTE combined with PSI, and each suspected lesion was detected by using 2-needle targeted puncture biopsy. There were 178 needles in total including 88 needles of prostate cancer and the positive rate of puncture points was 49.44% (88/178); there were 800 needles in total detected by using 10-needle systematic puncture biopsy including 203 needles of prostate cancer and the positive rate of puncture points was 25.38% (203/800); the positive rate of puncture points guided by TRTE combined with PSI puncture biopsy was higher than that by systematic puncture biopsy, and the difference was statistically significant ( χ2 = 40.337, P < 0.05). For prostate malignant lesions, the Spearman correlation analysis showed that TRTE score was positively correlated with pathological Gleason score ( r = 0.618, P < 0.05). Conclusion:TRTE combined with PSI-guided targeted puncture biopsy plays an important role in the diagnosis of prostate cancer, and it can effectively improve the positive rate of puncture points.

Objective:To compare the clinical results of different endovascular thrombus reduction techniques in the treatment of acute lower extremity arterial thrombosis.Methods:The clinical data of 96 consecutive patients with acute femoral popliteal arterial thrombosis who were treated with catheter directed thrombolysis (CDT) and mechanical thrombus aspiration system (PMT) between Jan 2016 and Dec 2018 at Cangzhou People's Hospital and Peking University People's Hospital were retrospectively analyzed.Results:Ninty-six patients underwent thrombolytic surgery,including 36 with CDT thrombolysis, 28 with AngioJet aspiration alone and 32 with Rotarex aspiration alone. Angiojet thrombus aspiration reduced thrombus rate by 89.3% (25/28) and clinical success rate by 92.8% (26/28).The thrombus reduction rate of Rotarex group was 87.5% (28/32), and the clinical success rate was 96.8% (31/32). In the CDT thrombolytic group, the thrombolytic reduction rate was 61.1% (22/36), including 8 patients who underwent thrombectomy and 6 patients with PMT, with a clinical success rate of 86.1% (31/36). The rate of distal arterial embolization, puncture point and local subcutaneous hematoma and vascular rupture was 21.4%, 10.7% and 2.1%, respectively. There were no amputation cases reported during a mean 13 months follow-up.The survival rate was 97.9%. The first-stage patency rate of 67.8%, while the second-stage artery patency rate of 85.7% during the follow-up.Conclusion:Compared with CDT, PMT has higher efficiency and lower complication rate in the treatment of acute lower extremity arterial thrombosis.

Objective:To investigate the clinical efficiency of gastrocnemius muscle flap combined with antibiotics loaded calcium sulfate in the treatment of postoperative infection and plate exposure of tibial plateau fracture in elderly patients.Methods:From January, 2015 to May, 2019, 21 elderly patients with postoperative infection and plate exposure of tibial plateau fracture were treated, including 14 males and 7 females with an average age of 72.6 years, ranging from 61 to 82 years. The average course of disease was 22.7 days, ranging from 6 to 91 days. The site of wound infection was at medial in 8 cases, lateral in 9 cases and bilateral in 4 cases. The size of wound ranged from 2.0 cm×3.5 cm to 5.0 cm×12.0 cm. All wounds were implanted with antibiotics loaded calcium sulfate and repaired by gastrocnemius muscle flap combined with skin graft after debridement. Muscle flap survival, wound healing, inflammatory index, fracture healing and knee joint function were recorded. The curative effect was evaluated by McKee infection treatment criteria and the knee joint function was evaluated by HSS scoring criteria.Results:All 21 muscle flaps survived. In 1 case, skin graft necrosis occurred in a small area, and the wound healed well after dressing change. One case had exudation which was clear and the bacterial culturing was negative, and the wound healed after 2 weeks of dressing change. The other incisions were healed in stage I, and the healing rate was 90%. All patients were followed-up for an average of 28.7(16-39) months. The redness and swelling occurred in 1 case without exudation after 2 months which disappeared after anti-infection treatment and didn't recur again. The infection recurred in 1 case after 5 months, and it which was controlled after debridement and plate removal. According to McKee criteria, 19 cases were cured, 1 improved and 1 recurred with an effective rate of 95.2%. The fracture healing time was from 3 to 7 months, with an average of 4.6 months. According to HSS scoring criteria, the knee joint function was excellent in 12 cases, good in 7 cases and moderate in 2 cases.Conclusion:After thorough debridement, gastrocnemius muscle flap combined with antibiotic loaded calcium sulfate can effectively control the infection, repair the wound, promote fracture union and restore limb function in the treatment of postoperative infection and plate exposure of tibial plateau fracture in elderly patients.

Objective To investigate the application value of lung ultrasonic on severe high altitude pulmonary edema.Methods A prospective, single-blind, case-control study was conducted. Sixty patients with severe high altitude pulmonary edema admitted to Qinghai University Affiliated Hospital from February 2015 to May 2017 were enrolled. The patients were divided into 2500-3000 m group, 3000-3500 m group and 3500-4200 m group according to different altitudes,with 20 patients in each group. The acute physiology and chronic health evaluationⅡ(APACHEⅡ) score was recorded before and 12 hours and 24 hours after treatment. The arterial partial pressure of oxygen (PaO2) was determined by blood gas analysis, and the oxygenation index (PaO2/FiO2) was calculated. Bedside ultrasound scanning was used to determine B line number and pulmonary artery pressure (PAP), and B line score was calculated to reflect lung water content. The correlation between B line score and PaO2/FiO2, PAP and APACHEⅡ scores at each time point was analyzed by Pearson correlation analysis.Results None of 60 patients died or exited, all of them were enrolled in the final analysis. There was no significant difference in PaO2/FiO2, PAP, APACHEⅡ score or B line score among different altitudes groups (allP > 0.05). Repeated measurement variance analysis showed that the effects of different altitudes on PaO2/FiO2, PAP, APACHEⅡ score and B line score were not statistically significant (F value was 0.312, 0.014, 1.098, 0.236, andP value was 0.340, 0.791, 0.733, and 0.986, respectively). The PaO2/FiO2, PAP, APACHEⅡ score and B line score in all groups were improved obviously from 12 hours after treatment, and the improvements at 24 hours were more than those at 12 hours (allP < 0.05). Repeated measurement variance analysis showed that the effect at different time points on PaO2/FiO2, PAP, APACHEⅡ score and B line score was statistically significant (F value was 1844.270, 121.690, 1173.175, 19426.968, allP < 0.001). The interaction effects of different altitudes and different time points on PaO2/FiO2, PAP, APACHEⅡ score and B line score were not statistically significant (F value was 0.304, 0.404, 1.172, 1.403, andP value was 0.875, 0.805, 0.327, and 0.591, respectively). Pearson correlation analysis showed that there was a significant negative correlation between B line score and PaO2/FiO2 before and after treatment (r value was -0.579, -0.522, and -0.386, allP < 0.01), indicating that the more the B line, the more severe the pulmonary edema, and the worse the oxygenation; with the decrease in B line after treatment, the pulmonary edema was gradually alleviated, and oxygenation was gradually improved. There was a significant positive correlation between B line score and APACHEⅡ score before and 24 hours after treatment (r value was 0.484 and 0.536, bothP < 0.01), indicating that the more the B line, the more severe the patient; with the decrease in B line after treatment, the patient's condition improved after treatment. There was only a weak correlation between B line score and PAP at 24 hours after treatment (r = 0.317,P = 0.014), indicating that PAP was not a sensitive indicator in the degree of pulmonary edema in patients.Conclusions The more the B line in patients with severe high altitude pulmonary edema,the more severe of the pulmonary edema, and the more severe of the patient. There was no significant correlation between the B line score and PAP. Pulmonary ultrasonography can still be used not only in the plain and low elevation areas, but in the high altitude areas, as a reliable method to evaluate the severity of pulmonary edema.

Objective To explore the distribution change and antimicrobial resistance of pathogens causing catheter associat‐ed urinary tract infection in ICU .Methods 500 cases of patients received by emergency department ICU in our hospital from 2012 April~ 2014 June were collected ,urine samples were collected by closed drainage bag after indwelling catheter in 3 ,7 ,14 ,21ds .By culture ,separation ,purification ,screening and identification and antimicrobial disc diffusion experiments ,distribution changes and resistantance of pathogens causing catheter related infections were analyzed .Results 358 strains were found in catheter associated urinary tract infections ,in which 175 strains were Gram‐positive bacteria ,mainly were Staphylococcus aureus (48 .57% ) and en‐terococci (46 .86% ) ,137 were Gram‐negative bacteria ,mainly were E .coli (56 .93% ) ,46 fungi ,mainly were Candida albicans (47 .83% );Gram‐positive bacteria showed a decreasing trend ,while Gram‐negative bacteria increased every year;resistance rates of Staphylococcus aureus and enterococci to penicillins ,cephalosporins and quinolones were more than 50% ;Escherichia coli and Kleb‐siella pneumoniae had strong resistance to penicillins ,cephalosporins and quinolones ;resistance rate of Pseudomonas aeruginosa to ampicillin ,sulbactam and ampicillin cefazolin up to 100% .Conclusion Escherichia coli is the major pathogens causing ICU catheter associated urinary tract infections;pathogens resistance are strong ,clinical monitoring should be strengthened .

Objective To understand the current status of Toxoplasma gondii(TOX)infection among pregnant women and to explore the risk factors in some areas of Lhasa City,Tibet. Methods From 2015 to 2016,3 districts(counties)of Lhasa City were chosen as the investigation sites,and 200 pregnant women in each district(county)were selected as the investigation objectives. Meanwhile,450 pregnant women from Xuzhou,Yangzhou,Wuxi cities in Jiangsu Province were chosen as the con?trol. Then the blood samples of the pregnant women both in Lhasa and Jiangsu were detected by ELISA for TOX antibodies IgG , IgM,and the detection results were analyzed and compared. In addition,the individual information of the pregnant women in Lhasa City was surveyed by questionnaires,and the related risk factors of TOX infection were analyzed. Results Among 600 pregnant women investigated in Lhasa City,there were 99 pregnant women with positive TOX antibodies,and the positive rate was 16.50%,which was significantly higher than that(5.11%)of the pregnant women in Jiangsu Province(P<0.05). There was no statistically significant difference among the 3 districts(counties)of Lhasa City in the positive rates of pregnant women (P>0.05). The positive rates of the women who preferred raw meat or had the intimate contact with animal were high. Conclu?sions Compared with Jiangsu Province,the infection rate of TOX among pregnant women in Lhasa City is high. Therefore,the comprehensive measures including health education,early examination and treatment should be taken actively,so as to prevent and control TOX infection in this area.