Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) block downstream signaling pathways by inhibiting receptor tyrosine kinase activity, consequently suppressing proliferation, invasion and metastasis of tumor cells. EGFR-TKIs have been proven to be highly effective in patients with late non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations, significantly better than chemotherapy. Third-generation EGFR-TKIs, such as osimertinib, have emerged as the first-line treatment for advanced NSCLC patients with sensitive EGFR mutations. However, there are still some patients who exhibit primary resistance upon initial treatment with EGFR-TKIs. The exact mechanism of primary resistance remains unknown, and may be related to factors such as the structure of EGFR mutation subtypes, concurrent mutations, BIM deletion polymorphism, and high expression of programmed cell death-ligand 1. This review summarizes the molecular mechanisms of primary resistance to EGFR-TKIs and discusses potential therapeutic strategies, with the goal of optimizing precision targeted therapy for NSCLC patients.

ObjectiveTo evaluate the predictive value of epicardial adipose tissue （EAT） parameters for microvascular obstruction （MVO） formation in patients with ST segment elevation myocardial infarction （STEMI） using cardiac magnetic resonance quantification. MethodsA total of 139 STEMI patients were included in this study， and various parameters such as EAT thickness， volume， and mass index were measured utilizing cardiac magnetic resonance. All included patients were divided into MVO group and non-MVO group according to whether MVO occurred. Differences in EAT related parameters between two groups were compared and correlation analysis was applied to evaluate the correlation between quantitative indicators of EAT and indicators such as infarct size and ejection fraction. Logistic regression analysis was used to identify the relevant risk factors for MVO formation. Receiver Operating Characteristic （ROC） curve analysis was performed to assess the predictive value of the epicardial adipose tissue （EAT） quality index and other indicators for the occurrence of MVO. ResultsCompared with non MVO group， patients in MVO group presented with higher peak troponin T levels， increase of neutrophil lymphocyte ratio （NLR） and C-reactive protein （CRP）， larger infarct size and compromised left ventricular ejection fraction （LVEF） （P<0.05）. Total EAT volume， EAT mass index， left atrioventricular EAT volume， left atrioventricular EAT mass index and thickness of EAT in the left atrioventricular groove were significantly higher in patients with MVO. Multivariate Logistic regression analysis demonstrated that NLR， peak troponin T levels and left atrioventricular EAT mass index were independent predictors of MVO. The ROC curve suggested that the left atrioventricular EAT mass index had the highest predictive power for MVO formation in STEMI patients. ConclusionThe parameters of EAT quantified by cardiac magnetic resonance serve as imaging biomarkers for predicting MVO formation in STEMI patients. These metrics enable risk stratification post-myocardial infarction and facilitate early identification of high-risk individuals， thereby supporting personalized therapeutic decision-making.

ObjectiveThis study aims to construct a reconstituted high-density lipoprotein (rHDL) delivery system loaded with kinsenoside (KD@rHDL), and to systematically evaluate its function in enhancing the phagocytosis of amyloid β-protein (Aβ) by microglia and improving the inflammatory state of microglia, as well as to preliminarily explore its potential application value in the treatment of Alzheimer’s disease (AD). MethodsKD@rHDL was prepared by the film hydration method combined with probe sonication and co-incubation. Its morphology was observed by transmission electron microscopy, and the particle size and Zeta potential were measured by dynamic light scattering. The encapsulation efficiency and drug loading were determined by high-performance liquid chromatography. The affinity between KD@rHDL and Aβ was analyzed by surface plasmon resonance (SPR) to assess its feasibility as a medium for Aβ clearance. At the cellular level, after treating mouse microglial cells (BV-2 cells) with KD@rHDL and adding fluorescently labeled Aβ, the phagocytic efficiency of microglia for Aβ was detected by confocal microscopy. Meanwhile, the CCK-8 method was used to evaluate the effect of KD@rHDL on cell viability to determine its safety. The trans-barrier transport ability of KD@rHDL was detected by Transwell assay. The expression levels of NLRP3 inflammasome and downstream inflammatory factor IL-1β in LPS-induced microglia were detected by Western blot to evaluate the regulatory effect of KD@rHDL on the inflammatory state of cells. ResultsCharacterization results showed that the successfully prepared KD@rHDL presented a typical discoid structure under transmission electron microscopy, with a uniform particle size distribution, an average particle size of approximately (14.4±0.24) nm, and a suitable negative Zeta potential, demonstrating good colloidal stability. The drug content determination results indicated that the encapsulation efficiency of KD@rHDL for kinsenoside was (42.24±1.30)%, and the drug loading was (6.03±0.19)%, indicating a good drug loading capacity. The CCK-8 assay results showed that in the set concentration range, the survival rates of BV2 and HT22 cells in the KD@rHDL treatment group were all above 90%, with no significant difference from the control group, indicating good cell safety of the formulation. The results of the Aβ phagocytosis experiment indicated that, compared with the Aβ oligomers (Aβo) group alone, the fluorescence signal intensity within microglia in the KD@rHDL treatment group was significantly enhanced, and a large amount of fluorescence-labeled Aβ was observed to accumulate intracellularly under a fluorescence microscope. The SPR assay results showed that rHDL had a strong affinity for Aβ, with an affinity constant reaching the nanomolar level. Transwell assay results indicated that KD@rHDL could effectively cross the bEnd.3 cell monolayer barrier and be taken up by BV2 and HT22 cells. Western blot assay results showed that high-dose KD@rHDL treatment could significantly reduce the expression level of NLRP3 protein in LPS-induced microglia and simultaneously down-regulate the maturation and secretion of IL-1β, indicating that KD@rHDL can effectively inhibit the activation of the NLRP3 inflammasome pathway and improve the neuroinflammatory state mediated by microglia. ConclusionThis study successfully constructed a reconstituted high-density lipoprotein delivery system loaded with kinsenoside (KD@rHDL). This nano-delivery system not only significantly enhances the phagocytic clearance ability of microglia towards Aβ, but also effectively inhibits the NLRP3/IL-1β-mediated inflammatory pathway, improving the inflammatory state of microglia. The above results indicate that KD@rHDL has a synergistic effect in promoting Aβ clearance and alleviating neuroinflammation, demonstrating potential therapeutic value for AD and providing new ideas and experimental basis for the development of subsequent AD treatment strategies.

OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery， and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio （INR） after taking mifepristone， clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes； for the selection of sex hormones after missed abortion， clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment， supplemented by Xian yimucao capsules， to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge， and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery， mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans， identification of drug-drug interactions， assessment of bleeding risks， and selection of postoperative sex hormones. Through full pharmaceutical monitoring， they ensure the safety of patients’ medication.

OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery， and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio （INR） after taking mifepristone， clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes； for the selection of sex hormones after missed abortion， clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment， supplemented by Xian yimucao capsules， to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge， and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery， mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans， identification of drug-drug interactions， assessment of bleeding risks， and selection of postoperative sex hormones. Through full pharmaceutical monitoring， they ensure the safety of patients’ medication.

Objective:To focus on clinical mini-lectures characterized by flexible teaching formats and significant challenges in scoring during supervision, systematically explore the roles and characteristics of raw scores (directly assigned by supervisory experts) and standard scores (revealing the relative position of instructors withing the group through Z-score conversion) in evaluating the teaching level and development trends of residency training teachers, investigate the feasibility of flexibly combining these two scoring methods, and provide new ideas for comprehensive, scientific, and objective teaching evaluations. Methods:In May 2024, 24 teachers who were supervised by three or more experts at a standardized training base for residents from 2019 to 2023 were selected as the research subjects. The study analyzed differences in mean rankings and development trends between raw and standard scores. Excel and SPSS were used for score transformation and statistical analysis of differences.Results:The mean rankings of standard scores differed from those of raw scores for 17 (70.83%) teaching staff members, among which 8 (33.33%) had a lower mean ranking of standard scores than raw scores, and 9 (37.50%) had an improved mean ranking of standard scores. For 10 (41.67%) teaching staff members, the differences in raw scores given among different supervisors were reversed after standardization conversion. The changes in the trends of scores for 17 (70.83%) teaching staff members throughout the years were inconsistent before and after score conversion.Conclusions:There were significant differences between the statistical results of standard scores and raw scores, and the two types of results evaluated the teaching level of teachers in terms of absolute situation and their relative positions in the entire teaching staff group, respectively. Therefore, combining the two types of scores with distinct characteristics for teaching evaluation can help teaching management departments comprehensively and objectively reveal the teaching level of teachers, while enhancing the confidence of faculty in teaching.

OBJECTIVE: To explore the clinical features of patients with necrotizing soft tissue infection (NSTI) and the related factors for sepsis, so as to provide a basis for early intervention and improvement of patients' prognosis. METHODS: A retrospective case series study was conducted to analyze the clinical data of NSTI patients admitted to the department of burns and wound repair surgery of Guangdong Provincial People's Hospital from October 2021 to December 2024. Demographic information, underlying diseases, infection characteristics, laboratory test results and etiological findings at admission, treatment status, occurrence of complications (including sepsis) and prognosis were collected. Univariate and multivariate Logistic regression analyses were used to identify the associated factors for sepsis in NSTI patients. Receiver operator characteristic curves (ROC curves) were plotted to evaluate the predictive value of individual and combined factors for sepsis. RESULTS: A total of 159 NSTI patients were enrolled, mainly middle-aged and elderly males. Most patients had comorbidities, including diabetes mellitus (110 cases, 69.2%) and hypertension (67 cases, 42.1%). The main infection site was the lower extremities (104 cases, 65.4%). Common symptoms included redness (96 cases, 60.4%), swelling (129 cases, 81.1%), local heat (60 cases, 37.7%), pain (100 cases, 62.9%), and skin ulceration or necrosis (9 cases, 5.7%). Imaging findings included soft tissue swelling (66 cases, 57.9%), gas accumulation (41 cases, 36.0%), and abnormal signal/density shadows (50 cases, 43.9%). Staphylococcus aureus was the main pathogenic bacterium [12.0% (31/259)], and drug-resistant Escherichia coli had the highest detection rate among drug-resistant bacteria [35.1% (13/37)]. Regarding debridement and repair, most patients (80 cases, 50.3%) underwent debridement ≥ 72 hours after admission, while only 10.1% (16 cases) received debridement within 6 hours. Most patients underwent multiple debridements, with 2 times of debridements being the most common (68 cases, 42.8%), and the maximum times of debridements reached 6. The largest number of patients received secondary suture (44 cases, 27.7%). In terms of complications, sepsis was the most common (66 cases, 41.51%), followed by acute kidney injury, respiratory failure requiring mechanical ventilation, and multiple organ dysfunction syndrome (MODS), while disseminated intravascular coagulation (DIC) was the least common. During the follow-up period, 9 patients (5.66%) were readmitted within 90 days, and 11 patients died, with a mortality rate of 6.92%. Univariate analysis showed that diabetes, coronary heart disease, gout, body temperature, heart rate, C-reactive protein, platelet count, total bilirubin, albumin, creatinine, out-of-hospital treatment, and out-of-hospital use of antimicrobial agents were significantly associated with sepsis in NSTI patients (all P < 0.05). Multivariate Logistic regression analysis showed that coronary heart disease [odds ratio (OR) = 30.085, 95% confidence interval (95%CI) was 2.105-956.935], C-reactive protein (OR = 1.026, 95%CI was 1.009-1.054), and total bilirubin (OR = 1.436, 95%CI was 1.188-1.948) were independent associated factors for sepsis in NSTI patients (all P < 0.05). ROC curve analysis revealed that the combination of the three predictors yielded the highest AUC for predicting sepsis in NSTI patients compared to any individual predictor [area under the curve (AUC) = 0.799 (95%CI was 0.721-0.878)]. CONCLUSIONS The clinical features of NSTI patients show certain regularity. Coronary heart disease, C-reactive protein, and total bilirubin are independent associated factors for sepsis in NSTI patients.
Humans ; Retrospective Studies ; Male ; Sepsis ; Soft Tissue Infections/microbiology* ; Female ; Middle Aged ; Aged ; Adult ; Prognosis ; Risk Factors ; Necrosis ; Logistic Models ; Fasciitis, Necrotizing

OBJECTIVE To investigate the current status of monitoring indicators related to the"Perioperative In-fection Control"in medical institutions above the secondary level in Guizhou Province,and to delve into the imple-mentation of key measures for infection prevention and control during the perioperative period for patients under-going surgical operations.METHODS Based on the"Implementation Plan for the'Perioperative Infection Control'Initiative in Guizhou Province",a"Case Investigation Form on Key Measures for Infection Prevention and Control During the Perioperative Period for Patients Undergoing Surgical Operation"was developed.A total of 138 medi-cal institutions participated in the case investigation,and a total of 2 128 cases were investigated.RESULTS The overall monitoring indicators for the"Perioperative Infection Control"initiative in the 138 medical institutions a-bove the secondary level in Guizhou Province were at a relatively low level.The skin cleansing compliance rate was 80.32％,the hair removal compliance rate was 16.43％,the prophylactic antibacterial drug administration rate within 0.5-1 hour before surgery was 55.94％and the antibacterial drug discontinuation rate within 24 hours after prophylactic medication for type Ⅰ incision surgeries was 56.48％.The hair removal compliance rate was higher in tertiary medical institutions(19.21％)than in secondary medical institutions(14.34％)(P=0.039).The distri-bution of the four monitoring indicators varied in clinical departments and surgery types,with statistically signifi-cant differences(P＜0.05).The preferred method for surgical site skin cleansing in medical institutions across the province was local wiping,primarily with clean water(57.21％).The primary method for hair removal was razors(68.82％),and hair removal on the day of surgery was most common(61.75％).CONCLUSIONS Conduc-ting a survey on the current status of"Perioperative Infection Control"initiative monitoring indicators in medi-cal institutions in Guizhou Province helps to understand the implementation of key measures for perioperative in-fection prevention and control and set intervention targets,thus providing references for establishing a dynam-ic monitoring indicator change mechanism.

Objective:To investigate the therapeutic efficacy and disruptive effects of Meropenem（MEM）-loaded microbubbles（MBs）combined with ultrasound targeted microbubble destruction（UTMD）technology on Escherichia coli and its biofilm.Methods:MEM-MBs were prepared using the thin-film hydration method，and their characterization was assessed using a Zeta potential analyzer，with morphological observations conducted under an optical microscope. An in vitro biofilm model of periprosthetic joint infection（PJI）caused by Escherichia coli was constructed，and the morphology of the biofilm and the distribution of MEM-MBs in the bacterial biofilm were observed under a laser confocal microscope after staining the biofilm with SYTO59 staining and DIL staining for Microbubbles. The biofilm morphology and the distribution of MEM-MBs in bacterial biofilm were observed under laser confocal microscope. The biofilms were randomly divided into 5 groups using a random number table：control，Meropenem（MEM），MEM-MBs，UTMD，and MEM-MBs+UTMD，with 12 samples per group. After applying the respective interventions，scanning electron microscopy（SEM）and laser scanning confocal microscopy（LSCM）were employed to observe the effects on the morphology and structure of Escherichia coli and its biofilm. Crystal violet staining was utilized to determine and compare the biofilm density among groups using a microplate reader. LSCM was also used to observe the biofilm thickness，while both LSCM and spread plate counting were employed to assess bacterial viability differences across groups.Results:①MEM-MBs meeting the experimental requirements were successfully constructed.②A dense Escherichia coli biofilm visible under both the naked eye and LSCM was established，with a thickness of（10.61 ± 0.17）μm and a proportion of dead bacteria within the biofilm of（16.8 ± 0.8）%.③MEM-MBs were observed to penetrate into all layers of the biofilm using LSCM.④The results of crystal violet staining showed a decreasing trend in the biofilm density of the control group，the MEM group，the MEM-MBs group，the UTMD group，and the MEM-MBs+UTMD group. There was no significant difference between the MEM group and the MEM-MBs group（ P＞0.05），while there was a significant difference in biofilm density between the other groups，as revealed by pairwise comparison（all P＜0.05）.⑤UTMD technique and MEM-MBs+UTMD could significantly disrupt the biofilm of Escherichia coli. LSCM results showed that，compared to the control group，the thickness of the biofilm was reduced in all other groups，with only the UTMD group and the MEM-MBs+UTMD group showing an increase in porosity（both P＜0.05）. In comparison with the MEM group and the MEM-MBs group，the UTMD group showed an increase in porosity，while the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05）. Additionally，compared to the UTMD group，the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05），based on laser confocal microscopy results.⑥The results of the plate counting and LSCM showed that，compared with the control group，clump counts decreased，and the proportion of dead cells increased in the MEM group，the MEM-MBs group，and the MEM-MBs+UTMD group（all P＜0.05）. Compared with MEM group and MEM-MBs group，the clump counts of UTMD group increased，the proportion of dead cells decreased（all P＜0.05）；the clump counts of MEM-MBs+UTMD group decreased，and the proportion of dead cells increased（all P＜0.05）.Compared with UTMD group（all P＜0.05），the clump counts of MEM-MBs+UTMD group decreased，while the proportion of dead cells increased（all P＜0.05）.⑦The results of scanning electron microscopy revealed that the network structure of Escherichia coli was completely destroyed in the MEM-MBs+UTMD group. Conclusions:UTMD technology combined with MEM-MBs exerts a significant disruptive effect on the morphology and structure of Escherichia coli biofilm and significantly enhances bactericidal efficacy.

Objective:To explore the effectiveness of designing a training program for faculty supervisory specialists guided by adult learning theory.Methods:Based on the theory of adult learning, we designed a training program for faculty supervisory specialists in standardized residency training. A questionnaire survey was conducted to collect satisfaction and learning outcomes from 31 trainees who participated in this training program from 2019 to 2022. SPSS 25.0 was used to conduct nonparametric tests of supervisory course ratings for four core teaching activities in 2019 and 2022.Results:The study showed that 100.00% (31/31) of training participants were very satisfied or satisfied with the training content and training methods, 96.77% (30/31) were very satisfied or satisfied with the training sessions, and 90.32%(28/31) of training participants felt that they had mastered the supervisory requirements. The course grades for mini-lectures ( Z=-3.01, P<0.05) and overall course supervision ( Z=-2.47, P<0.05) were significantly different between 2019 and 2022. Compared with 2019, the number of externally assigned instructors and externally assigned assessment experts increased significantly in 2022. The training program for faculty supervisory specialists has a high value for promotion. Conclusions:The supervisory specialist training program designed under the guidance of adult learning theory helps increase the interest of training participants in the training program and ultimately improves the effectiveness of the training program.