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.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Aim To observe the mechanism of salvian-olic acid B(SalB)against oxygen glucose deprivation/re-oxygenation(OGD/R)injury in H9c2 cardiomyo-cytes.Methods The protective concentration of SalB against OGD/R-injured H9c2 cardiomyocytes was screened by CCK-8 assay.The levels of lactate dehy-drogenase(LDH),aspartate transaminase(AST)and creatine kinase(CK)were detected by ELISA kit.The mechanism of action of SalB on OGD/R-injured H9c2 cardiomyocytes was explored using high-through-put sequencing of the transcriptome.The binding of SalB to differential proteins was assessed using molecu-lar docking assays.Fatty acid content was determined using free fatty acid kits.The relative expressions of mRNA and protein of differential genes were verified by RT-qPCR and Western blot.The causal relationship between the target of action of SalB and heart failure was examined by Mendelian randomization experiment.Results SalB protected OGD/R-injured H9c2 cardio-myocytes and significantly reduced the levels of CK,LDH and AST compared with the blank control group.One hundred differential genes were screened by tran-scriptome sequencing,which were mainly involved in fatty acid elongation,central carbon metabolism of cancer,tryptophan metabolism pathways.Molecular docking showed that SalB had good binding energy to differential proteins.The mRNA and protein expression of core differential genes Elovl6,Echs1 and Acot1 were consistent with the transcriptome sequencing results.SalB reduced fatty acidsafter OGD/R injury.Mende-lian randomization experiments suggested that SalB might reduce the risk of heart failure through fatty acid metabolism,thereby reducing the risk of heart failure.Conclusion SalB can protect H9c2 cardiomyocytes after OGD/R injury by down-regulating Elovl6,Echs1 and Acot1 expression through the fatty acid metabolism pathway.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Objective:To investigate the efficacy and safety of transurethral water vapor thermal therapy(WVTT)using the Rezūm system for benign prostatic hyperplasia(BPH)in the real world.Methods:A total of 181 patients with BPH were recruited from the Second Affiliated Hospital of Nanjing Medical University from August 2022 to December 2023,of whom 173 patients were treated with WVTT using the Rezūm system,while 8 patients were treated with WVTT combined with TURP.They were followed up at 1,3,and 6 months postoperatively to assess changes in the IPSS,QoL,Qmax,IIEF-5,and the occurrence of any complications.Results:All 181 surgeries in this group were successfully completed.The operation time of the Rezūm system was(4.6±1.4)mi-nutes.The postoperative indwelling catheterization time was(8.0±2.1)days.With a follow-up of at least 6 months,there was a significant decrease in PV,IPSS and QoL,and a remarkable increase had been found in Qmax as well(P＜0.05).There was no sig-nificant difference in IIEF-5 before and after the operation(P＞0.05).In this groups of patients,postoperative complications mainly included 95 cases(52.5％)of gross hematuria,6 cases(3.3％)of retrograde ejaculation,5 cases(2.8％)of urethral stricture,4 cases(2.2％)of prostatitis,and 10 cases(5.5％)of urinary tract infection.Four cases(2.2％)underwent surgical retreatment for BPH after surgery.Conclusion:In the real world,the use of Rezūm thermal steam ablation system for the treatment of BPH has sat-isfactory short-term effect,short surgical time,and significant improvement in IPSS,QoL,Qmax,which does not adversely affect sexu-al function.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Objective: To evaluate the clinical efficacy of costal cartilage septal-columellar composite grafts in refining nasal tip aesthetics for secondary unilateral cleft lip nasal deformities, and to provide a reference for clinical treatment. Methods: This study has been approved by the institutional medical ethics committee and informed consent was obtained from the patients. A total of 31 patients underwent surgery with a costal cartilage strut-septum complex stent graft. The follow-up period was a minimum of 6 months. Anteroposterior, lateral, and supine photos of the patient were taken before and after the operation. The following measurements were obtained: nasal tip projection (NTP), nasofrontal angle (NFA), nasolabial angle (NLA), nasal tip alar angle (NAA), and nasal tip tangent angle (NTA). Nostril-related indices [nostril area (S), nostril height (h1), nostril width (w), and nasal sill height (h2)]) were measured before and after surgery, and cleft/non-cleft side ratios were calculated. Satisfaction with nasal tip aesthetics was investigated using the visual analogue scale (VAS). All measurements were made using preoperative photographs and the most recent follow-up photographs of the patients. Results The follow-up period ranged from 6 to 49 months, with an average of 28 months. All patients underwent healing Results: The follow-up period ranged from 6 to 49 months, with an average of 28 months. All patients underwent healing by first intention. Compared with preoperative measurements, postoperative NTP (preoperative 0.48 vs. postoperative 0.55), NLA (preoperative 83.98° vs. postoperative 100.80°), and NAA (preoperative 160.30° vs. postoperative 168.40°) were significantly increased (P < 0.05). NFA (preoperative 139.20° vs. postoperative 133.50°, P < 0.05) and NTA (preoperative 43.76° vs. postoperative 35.80°, P = 0.062) were decreased. On the cleft versus non-cleft sides, the ratios of S (preoperative 1.10 vs. postoperative 0.94, P < 0.05), w (preoperative 1.10 vs. postoperative 1.02, P = 0.194), h1 (preoperative 0.71 vs. postoperative 0.90, P < 0.05), and h2 (preoperative 0.53 vs. postoperative 0.79, P = 0.065) were all near 1. Satisfaction with postoperative results was fairly high. Conclusion The costal cartilage strut-septum complex stent can effectively correct the deflection and collapse of the nasal tip in patients with unilateral cleft lip nose deformity. The postoperative long-term effect is relatively stable.

Objective To establish an effective model for distinguishing glandular prodromal lesions(PGL)mixed with ground-glass nodules(mGGN)from minimally invasive adenocarcinoma(MIA)on CT based on artificial intelligence.Methods A retrospective analysis was conducted on the clinical and CT image data of 180 patients with lung adenocarcinoma confirmed by surgical pathology and with CT manifestations of mGGN in the First Affiliated Hospital of Wenzhou Medical University from January 2017 to June 2023,inclu-ding 66 patients with PGL and 114 patients with MIA.Patients were divided into the training set(n=144)and the test set(n=36)in an 8∶2 ratio using a completely random method.The quantitative parameters and radiomics features of the lesions in CT images were automatically extracted using artificial intelligence soft-ware(United Imaging Research Platform uRP).By incorporating the most obvious correlation features of omics through dimensionality reduction,five machine learning classifiers were established,including logistic regression(LR),support vector machine(SVM),Random forest(RF),Gaussian process(GP),and Decision Tree(DT).The classifier with the training set highest area under the curve(AUC)was selected as the best radiomics model,and output the result as radiomics score(Rad-score).The clinical information,CT morpho-logical characteristics and quantitative data of the two groups were included in the multivariate logistic regres-sion analysis to screen the independent influencing factors for effectively differentiating PGL and MIA,and a clinical model was established.Finally,a comprehensive prediction model was constructed based on Rad-score and clinical risk factors.The diagnostic performance of the three models was evaluated by using the AUC,sen-sitivity,specificity and accuracy of receiver operating characteristic(ROC)curve.Results Eleven radiomics features for distinguishing PGL from MIA were obtained through LASSO dimensionality reduction.Among the five machine learning classifiers,GP has the best diagnostic performance,with AUC of 0.865 in the train-ing set and 0.762 in the test set,respectively.Univariate and multivariate logistic regression analyses were used for clinical feature screening.The clinical model was constructed by using the average CT value,average long and short diameter,and solid partial long diameter of mGGN,and the AUCs of the training set and the test set were 0.870 and 0.794,respectively.The comprehensive prediction model demonstrated superior diag-nostic performance,with AUC,sensitivity,specificity,and accuracy in the training set being 0.948,81.1%,91.2%and 87.5%respectively,while 0.883,76.9%,91.3%and 86.1%respectively in the test set.Conclu-sion The comprehensive prediction model established based on the quantitative and omics feature analysis of pulmonary nodules by artificial intelligence can well distinguish mGGN mixed with PGL from MIA on CT,and can be used to guide clinical treatment decisions.

Objective To explore the effect of ionizing radiation on the fertility of male mice and its offspring and the intergenerational and transgenerational genetic effect mechanism of ionizing radiation through sperm DNA methylation sequencing.Methods Eight-week-old(8 w)C57BL/6 male mice were irradiated with 60Co radiation source at a dose of 3 Gy(3 Gy-F0 group,n=60)and non-irradiated mice of the same age were used as controls(0 Gy-F0 group,n=60).Afetr 5-,6-,7-,8-,9-,10-,11-,and 12-week radiation,the mice began to breed with healthy females,and the first generation(F1 generation)male mice then breed with healthy female mice to obtain the offspring(F2 generation)male mice.The structure of testis was detected by hematoxylin-eosin staining;serum follicle-stimulating hormone(FSH),testosterone(T)and luteinizing hormone(LH)levels were determined by enzyme-linked immunosorbent assay.Automatic sperm analysis system was used to detect sperm concentration and activity.The DNA of F0 generation sperm was extracted and analyzed by genome-wide DNA methylation sequencing.MassARRAY methylation sites were detected in sperm DNA of F1 generation mice and verified by quantitative polymerase chain reaction(qPCR).Results Compared with the 0 Gy-F0 group,male mice in the 3 Gy-F0 group gradually regained their reproductive ability 7 weeks after ionizing radiation.There was no significant difference in the number of surviving offspring between the 3 Gy-F0 group and 0 Gy-F0 group 10-11 weeks after radiation(P＞0.05).There were no significant differences in body weight,testicular morphology,or sperm concentration of F1 generation mice between the 3 Gy-F1 group and the 0 Gy-F1 group(all P＞0.05).However,compared with the 0 Gy-F1 group,the contents of LH,FSH and T in the 3 Gy-F1 group were all decreased(all P＜0.05),the testicle volume,total sperm motility rate,forward motility rate and the fertility were considerably decreased(all P＜0.05).DNA methylation sequencing showed that more differentially methylated genes were enriched in the pathway regulating microtubule formation.MassARRAY methylation sites analysis showed that the methylation level of Mid1 was significantly increased(P＜0.05 or P＜0.01).Mid1 was verified down-regulated in Fl and F0 sperm by qPCR(P＜0.05 or P＜0.01).However,there were no significant differences in volume of testes,testicular index,sperm concentration,sperm motility,hormone levels or Mid1 expression level between 0 Gy-F2 and 3 Gy-F2 mice in F2 generation male mice(all P＞0.05).Conclusion Sperm damage in mice caused by ionizing radiation at a dose of 3 Gy can recover by itself.However,it may decrease sperm activity by regulating Mid1 methylation level of sperm in F1 mice,thus affect the fertility of F1 mice,but has no effect on the fertility of male F2 mice.