ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

ObjectiveTo observe the prognosis effect of soluble programmed death ligand-1（sPD-L1） in treating patients with advanced lung adenocarcinoma treated with epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs） and the influence of Yiqi Yangyin Jiedu prescription. MethodA prospective cohort-controlled study was conducted to enroll patients treated with EGFR-TKIs in the first line of treatment，who were admitted to the Oncology Department of Longhua Hospital and Shanghai Chest Hospital from May 1^st， 2021 to June 30^th， 2023， and they were evaluated as non-progressive and identified with deficiency of Qi and Yin after one month of treatment. The patients were divided into an exposed group （EGFR-TKIs combined with Yiqi Yangyin Jiedu prescription） and a non-exposed group （EGFR-TKIs alone）according to whether or not they were treated with Yiqi Yangyin Jiedu prescription and were treated until disease progression， or death and intolerable adverse reactions occurred. The enzyme-linked immunosorbent assay （ELISA） was applied to detect the level of sPD-L1 in patients at the time of enrollment and disease progression，and Cox risk proportionality model was used to analyze the independent prognostic factors affecting disease progression of patients treated with EGFR-TKIs. ResultA total of 90 patients （39 in the exposed group and 51 in the non-exposed group） undergoing disease progression after EGFR-TKI treatment were enrolled. At the time of enrolment and after disease progression，the levels of serum sPD-L1 in the 90 patients were 12.06 （27.54） ng·L^-1 and 41.99 （62.93） ng·L^-1，respectively. Compared with that at the time of enrollment， the serum sPD-L1 level in the 90 patients was significantly increased after disease progression （P<0.01）. The serum sPD-L1 level in patients in the exposed group was 12.27 （24.78） ng·L^-1 and 29.57 （61.12）ng·L^-1 respectively at the time of enrolment and after disease progression. In the non-exposed group， patients had serum sPD-L1 levels of 11.81 （28.46） ng·L^-1 and 49.54 （74.12） ng·L^-1 respectively at the time of enrolment and after disease progression. Compared with that at the time of enrollment， the serum sPD-L1 level in the two groups of patients was significantly increased after disease progression （P<0.01）. In addition， compared with that in the non-exposed group， the sPD-L1 level in the exposed group was greatly reduced after disease progression（P<0.01）. Cox multifactorial analysis showed that sPD-L1 level and age at the time of enrolment were associated with patients' progression-free survival（PFS），and that low levels of sPD-L1 （<12.06 ng·L^-1） prolonged the PFS and reduced the risk of disease progression in patients treated with EGFR-TKIs compared with high levels of sPD-L1. ConclusionElevated sPD-L1 level is a poor prognostic factor for the long-term efficacy of EGFR-TKIs，and treatment with Yiqi Yangiin Jiedu prescription can down-regulate sPD-L1 level of patients treated with EGFR-TKIs.

Objective : To explore the role of lysophosphatidylcholine acyltransferase 3(LPCAT3) in Erastin-induced ferroptosis of acute myeloid leukemia(AML) cells and its related molecular regulatory mechanisms. Methods : Tetrazolium salt(MTS) method was used to detect the sensitivity of different AML cells to the classic ferroptosis inducer Erastin, real time quantitative polymerase chain reaction(qPCR) was used to detect the basal expression level ofLPCAT3mRNA, and the correlation between them was analyzed. Lentivirus-mediatedLPCAT3overexpression AML cell lines(OE group) and negative control lines(NC group) were constructed. After Erastin intervention, MTS, flow cytometry, and micromethods were used to detect cell viability, lipid reactive oxygen species(ROS), and Malondialdehyde(MDA), respectively. qPCR and Western blot were used to detect unfolded protein response(UPR) classic pathway signaling molecules(PERK, ATF4, GRP78, etc.) expression levels. The above ferroptosis-related indicators were detected after combined intervention with the UPR inhibitor 4-phenylbutyric acid(4-PBA), and the regulatory relationship was analyzed. Results : Four different types of AML cells had different sensitivities to ferroptosis, among which K562 cells were relatively insensitive. The IC50of the four types of AML cells to Erastin was negatively correlated with the expression level ofLPCAT3(r=-0.919,P<0.001). After Erastin intervention, the cell viability of K562 cells in the OE group was significantly inhibited by Erastin compared with the NC group(P<0.001), and the levels of lipid ROS and MDA increased(P<0.001). The results of qPCR and Western blot showed that, compared with the NC group, the mRNA and protein expression of UPR classic pathway moleculesPERK,ATF4, andGRP78mRNA and protein increased in the OE group(P<0.01). After inhibiting the UPR pathway by 4-PBA, the viability of K562 cells decreased(P<0.01), and lipid ROS and MDA levels increased(P<0.01) compared with the uninhibited state. Conclusion Overexpression ofLPCAT3can promote ferroptosis in K562 cells, and this process is negatively regulated by the classical UPR pathway PERK/ATF.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections.Herein,we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering(SERS)and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease(MNase)in serum samples.The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine(TMB)molecules to SERS-enhanced oxidized TMB(oxTMB),accompanied by the color change from colorless to blue.In the presence of S.aureus,the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads(MBs)to release alkaline phosphatase(ALP),which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away.Using this"on-to-off"triggering strategy,the target S.aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode.Meanwhile,the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis(n=7)and healthy participants(n=3),as well as monitored the prog-nostic progression of the disease(n=2).Overall,benefiting from highly active and dense"hot spot"substrate,MNase-mediated cascade response strategy,and colorimetric/SERS dual-signal output,this methodology will offer a promising avenue for the early diagnosis of S.aureus infection.

Objective:To analyze the application of situational teaching method based on the OBE concept in the teaching of Emergency and Critical Care Nursing course for undergraduate nursing students,and evaluate its effect on their clinical practice and internship adaptability.Methods:The third-year nursing students from 2018 to 2021 in a university in Anhui Province were selected as the research objects.Thirty students were selected as the experimental group each academic year,and taught using situational teaching method based on the OBE concept.Another 30 students from the same academic year were selected as the control group and taught using the conventional teaching method.The course teaching evaluation and course assessment scores of the two groups were compared,and the clinical practice ability and internship adaptability were compared before and after 3 months of hospital internship.Results:There was no significant difference in the course teaching evaluation and course assessment scores between the two groups(P＞0.05).The case analysis score of the experimental group was higher than that of the control group(P＜0.01).The scores of each dimension and total score of the clinical practice ability scale after internship in the observation group were higher than those in the control group(P＜0.05),and the scores of each dimension and total score of the internship adaptability scale were also higher than those in the control group(P＜0.05).Conclusion:Based on the concept of OBE,the situational teaching method is beneficial to improving the ability of case analysis,and enhancing the clinical practice ability and internship adaptability of nursing students.

IgA nephropathy（IgAN）is the most common primary glomerular disease，characterized by the deposition of IgA in the glomerular mesangial area. IgAN is a progressive disease with a protracted and relapsing course. Approximately 50%~75% of adult IgAN patients experience renal function deterioration and eventually progress to end-stage kidney disease（ESKD）within 20 years after diagnosis. Among patients with onset in childhood，about 30% ultimately progress to ESKD after 20 years of long-term follow-up. In recent years，numerous studies have continuously explored important signaling pathways and key molecules in its pathogenesis. This review introduces the therapeutic advances in IgAN，aiming to provide better treatment options for clinicians.

Objective:To observe the effects of shoulder-three-needle therapy plus joint mobilization and extracorporeal shock wave therapy(ESWT)in improving symptoms and pain mediators in patients with scapulohumeral periarthritis.Methods:A total of 82 patients with scapulohumeral periarthritis were randomized into a control group and an observation group by the random number table method,with 41 cases in each group.The control group was treated with ESWT.The observation group was treated with additional shoulder-three-needle therapy plus joint mobilization based on the treatment in the control group.After 4 weeks of treatment,shoulder joint function,pain mediators,inflammatory factor levels,and clinical efficacy were compared between the two groups.Results:The total effective rate and the score of shoulder joint function in the observation group were higher than those in the control group(P<0.05).After treatment,the levels of serum pain mediators substance P(SP),5-hydroxytryptamine(5-HT),and prostaglandin E2(PGE2),as well as inflammatory factors interleukin(IL)-6,tumor necrosis factor(TNF)-α,and C-reactive protein(CRP)decreased significantly in both groups(P<0.05).And,the serum pain mediators SP,5-HT,and PGE2,and the levels of inflammatory factors IL-6,TNF-α,and CRP in the observation group were all lower than those in the control group(P<0.05).Conclusion:Shoulder-three-needle therapy plus joint mobilization and ESWT has a better curative effect than ESWT alone in treating scapulohumeral periarthritis.It can effectively improve the clinical symptoms,reduce the levels of pain mediators and inflammatory factors,and increase shoulder joint function.

Objective:To construct a biosafety evaluation index system for major emergency public health events in medical institutions.Methods:Based on previous laboratory biosafety evaluation work, relevant regulations and standards on biosafety in China were collected through literature research and expert consultations. Candidate indicators for constructing the biosafety evaluation system for major emergency public health events in medical institutions were selected, and a framework was established. Two rounds of expert questionnaires were conducted to determine the content of the index system based on experts′ evaluation, and each indicator′s relevance and importance were scored. Finally, two rounds of Delphi consultations were carried out, and the Analytic Hierarchy Process (AHP) was applied to calculate the weights of indicators.Results:The response rates for the total four rounds of questionnaire surveys were all 100%. The first two rounds focused on determining the framework, while the latter two focused on determining the weights for each indicator. The authority coefficients of the expert consultations for the two rounds of weights were 0.65 and 0.70, respectively, indicating the reliability of the research results. In the final round of survey, the Kendall′s coefficients of concordance at each level were all greater than 0.1. Through statistical testing, the P-values were all less than 0.05, indicating good coordination of expert opinions. Ultimately, we established an operational biosafety evaluation system for major emergency public health events in medical institutions, consisting of 4 primary indicators, 26 secondary indicators, and 119 tertiary indicators, with additional deduction items, bonus items, unacceptable items, and monitoring indicators.Conclusions:Based on scientific theory, a biosafety evaluation system for major emergency public health events in medical institutions was constructed, achieving the integration of routine and emergency measures. This system can be used for self-assessment of laboratory biosafety during emergency public health events, addressing the lack of unified standards in biosafety evaluation. Through regular self-assessment, it can enhance the level of biosafety management in medical institution laboratories, to realize the value of application and dissemination.

Objective To analyze the characteristics of facial and tongue chromaticity parameters in patients with gastrointestinal tumors by setting the inspection image characteristics of patients with gastrointestinal tumors as the main research content;To establish an auxiliary diagnostic model for gastrointestinal tumors.Methods One-way ANOVA,t-test,Mann-whitney U test,canonical correlation analysis and Spearman statistical methods were used to analyze the characteristics of inspection image indexes and correlation of tumor markers of the 391 cases in the control group and 359 patients with gastrointestinal tumors.Machine learning methods such as SVM,Random Forest,KNN,Naive Bayes,XG Boost and Ada Boost were used to establish an auxiliary diagnostic model for gastrointestinal tumors.Results In terms of facial indicators,there were differences in F-R,F-G and F-B indicators among the control group,early-stage gastrointestinal cancer patients,and mid-to late-stage gastrointestinal cancer patients,in the comparison of tongue features among,TC-L,TB-L and TB-a of the control group,patients with early gastrointestinal tumors,and patients with intermediate and advanced gastrointestinal tumors showed a gradual downward trend;the AUC of the auxiliary diagnosis model of gastrointestinal tumor disease based on the chromaticity parameters of face tongue image constructed by Ada Boost algorithm was 0.930.Conclusion The auxiliary diagnostic model of gastrointestinal diseases constructed by facial and tongue images has good diagnostic effect,which can provide objective data support for in-depth exploration of the complex relationship between diagnosis and disease.