Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） acetic acid（D1）and 4-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） butanoic acid （D2）. Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro （P<0.01）. However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Aim To investigate the related influencing factors of major adverse cardiovascular events(MACE)in coronary heart disease(CHD)patients with type 2 diabetes mellitus(T2DM)based on prognostic nutritional index(PNI),and to construct a prediction model.Methods The clinical data of 391 patients with CHD combined with T2DM who were hospitalised in the Department of Cardiovascular Medicine of Hebei Provincial People's Hospital from Janu-ary 2022 to January 2023 were collected and followed up for 1 year,and were divided into the MACE group(n=99)and the non-MACE group(n=292)according to the presence or absence of the occurrence of MACE,and were divided into the training set(n=273)and the validation set(n=118)in a ratio of 7:3 by using the computer-generated random number method,and the patients in the training set were divided into the MACE(n=67)group and the non-MACE group(n=206)according to whether they had MACE or not.Lasso regression was used to screen the relevant influencing factors and to construct the prediction model of the column-line diagram,and the prediction model was validated by plotting receiv-er operating characteristic(ROC)curve,calibration curve,decision curve analysis(DCA),and clinical impact curve(CIC).Results Lasso regression showed that the use of angiotensin receptor neprilysin inhibitor(ARNI),fasting blood glucose(FBG),C-reactive protein(CRP),platelet to lymphocyte ratio(PLR),lipoprotein(a)(Lp(a)),and PNI were the predictors of the occurrence of MACE in patients with CHD combined with T2DM.A column-line graph pre-diction model was constructed and validated based on the above predictors,and the area under the ROC curve(AUC)was 0.838(95％CI:0.778～0.898)in the training set and0.872(95％CI:0.803～0.942)in the validation set,with a good discriminatory degree of the model,and the C-values of the calibration curves in the training set and the validation set were 0.838 and 0.872,respectively,with good fit.The results of the decision curve analysis and the clinical impact curve showed that the column-line graph prediction model had a higher net yield of MACE in patients with CHD combined with T2DM,with high clinical utility.Conclusion PNI is an influential factor in the occurrence of MACE in patients with CHD combined with T2DM,and the column-line graphical model constructed on the basis of predictors such as PNI is con-venient for clinical use and has high predictive value in predicting the occurrence of MACE in patients with CHD combined with T2DM.

Objective To investigate the correlation between the expression of microRNA-4319(miRNA-4319)and microRNA-4262(miRNA-4262)in early gastric carcinoma tissue and postoperative recurrence after endoscopic submucosal dissection(ESD).Methods From May 2018 to March 2020,396 patients with early gastric carcinoma who underwent ESD were regarded as the disease group,meantime,98 patients with normal gastric mucosa gastritis confirmed by pathological examination were as the control group.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)method was applied to detect the relative expression levels of miRNA-4319 and miRNA-4262 in tissues;follow up on postoperative recurrence of early gastric carcinoma patients,and the expression levels and clinical pathological characteristics of miRNA-4319 and miRNA-4262 were compared between recurrent and non recurrent patients.Multivariate Logistic regression analysis was applied to analyze the influencing factors of recurrence in early gastric carcinoma patients after ESD;receiver operating characteristic curve(ROC curve)was applied to analyze the predictive value of miRNA-4319 and miRNA-4262 in early gastric carcinoma tissue for recurrence after ESD.Results The expression levels of miRNA-4319 and miRNA-4262 in the disease group were lower than those in the control group,the differences were statistically significant(P＜0.05);The expression levels of miRNA-4319 and miRNA-4262 in the recurrence group were decreased,and the proportion of submucosal invasion was increased,the differences were statistically significant(P＜0.05).The depth of invasion to the submucosal level(OR=3.158,95％CI:1.395～7.151)was a risk factor for recurrence after ESD in patients with early gastric carcinoma(P＜0.05),and miRNA-4262 ≥ 0.76(OR=0.561,95％CI:0.370～0.852)and miRNA-4319 ≥ 0.69(OR=0.482,95％CI:0.255～0.911)were protective factors for recurrence after ESD in patients with early gastric carcinoma(P＜0.05);The area under the curve(AUC)of miRNA-4319,miRNA-4262 and their combination for predicting recurrence after ESD in patients with early gastric carcinoma was 0.889(95％CI:0.854～0.918),0.914(95％CI:0.882～0.940)and 0.964(95％CI:0.940～0.980),respectively,which was superior to the individual predictions of miRNA-4319 and miRNA-4262 respectively(P＜0.05).Conclusion MiRNA-4319 and miRNA-4262 are low expressed in tissues of early gastric carcinoma patients,they are closely related to postoperative recurrence after ESD.

Objective To measure and analyze anatomic parameters of resected distal femurs and proximal tibias in Kaschin-Beck disease(KBD)and osteoarthritic(OA)knees which fit for total knee arthroplasty(TKA),so as to provide basis for designing suitable knee prosthesis for KBD patients.Methods A total of 154 knees(75 KBD and 79 OA)fitting for TKA underwent three-dimensional reconstruction;resection of distal femurs and proximal tibias was simulated during TKA.We measured the distal femoral mediolateral(fML),lateral anteroposterior(fLAP),medial anteroposterior(fMAP),medial condylar width(fMCW),lateral condylar width(fLCW)and fML/fLAP aspect ratio,proximal tibial mediolateral(tML),middle anteroposterior(tAP),medial anteroposterior(tMAP),lateral anteroposterior(tLAP)dimension,and tML/tAP aspect ratio to compare the morphometric differences between KBD and OA knees.Results The measured anatomic parameters of resected distal femurs and proximal tibias in both male and female patients of KBD group were smaller than those of OA knees(P＜0.01).We also found that KBD group had larger distal femur fML/fLAP and proximal tibia tML/tAP aspect ratios than those of OA knees(P＜0.01).This indicated that under a given AP dimension,KBD knees need an oval-shaped prosthesis with a wider ML length and more spherical-shaped prosthesis with relatively narrow ML dimensions in OA knees.Conclusion The anatomy of distal femurs and proximal tibias shows significant differences in size and shape between KBD and OA knees,which provides theoretical basis for designing proper knee prosthesis for KBD patients.

Objective To investigate the improvement effect of microsurgical varicocelectomy with vein ligation on scrotal pain and the related factors affecting the improvement of postoperative pain.Methods A retrospective analysis was conducted on the clinical data of 110 patients who underwent microsurgical inguinal varicocelectomy in Central Theater Command General Hospital from November 2021 to June 2023.The degree of pain before and after the operation was evaluated by Numerical Rating Scale(NRS).The pain relief rate,the occurrence of postoperative complications and the overall satisfaction of patients were evaluated.The semen and hormone levels of the patients before and after the operation were analyzed.Univariate and multivariate linear regression analyses were performed to investigate the relationship between clinical variables and postoperative 7-day NRS score.Results The average number of ligated veins during the operation was(6.60±3.76);postoperative satisfaction of patients was(4.23±1.08)points;complications occurred in 7 patients after the operation;after 3 months of follow-up,the overall pain relief rate was 92.73%(102/110).Compared with those before the operation,the NRS score of the patients significantly decreased 7 days after the operation,and the levels of total sperm motility,prolactin and testosterone increased 3 months after the operation,while the levels of serum follicle-stimulating hormone(FSH)and luteinizing hormone(LH)decreased,the differences were statistically significant(P<0.05).The univariate and multivariate linear regression analyses showed that the Dubin-Amelar classification of varicocele(P=0.045),operation time(P=0.049),and number of ligated veins(P=0.024)were significantly correlated with the change of postoperative 7-day NRS score.Patients with 1 to 4,5 to 10,and>10 intraoperative ligation veins were analyzed,and pain relief rates 3 months after the operation were 77.78%(28/36),100%(58/58),and 100%(16/16),respectively,with statistically significant difference(χ2=17.732,P<0.001).Conclusion Microsurgical varicocelectomy can effectively relieve scrotal pain and improve semen quality.Moreover,the relief of postoperative pain is related to the Dubin-Amelar classification of varicocele,the sufficient number of ligated spermatic veins,and the surgical experience of the surgeon.

Objective To analyze the multi-target mechanism of Paeoniflorin in the intervention of oral submucosal fibrosis(OSF)systematically,based on molecular dynamics simulation and network pharmacology.Methods Identify potential targets of Paeoniflorin were predicted by using database.OSF-related disease targets and identified drug-disease intersecting targets were screened.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were conducted to validate the molecular binding capabilities between Paeoniflorin and core targets.Finally,molecular dynamics simulations were performed to verify binding stability.Results A total of 20 overlapping targets were identified,including key genes such as transforming growth factor(TGF)-β1,interleukin(IL)-6,and tumor necrosis factor(TNF)-α.TGF-β1,IL-6,and TNF formed the core hub.The enrichment analysis revealed that the target molecules were significantly enriched in the TGF-β1,phosphatidylinositol 3-kinease-actin(PI3K-Akt),and nuclear factor κB(NF-κB)signaling pathways.Molecular docking confirmed high affinity binding of Paeoniflorin to targets including TGF-β1,while molecular dynamics simulations verified stable interactions between Paeoniflorin and both TGF-β1 and B-cell lymphoma-2 targets.Conclusion This study revealed that Paeoniflorin inhibits the inflammatory-fibrotic cascade of OSF through synergistic regulation of TGF-β1/Smad,PI3K-Akt and NF-κB pathways.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.