Antimicrobial resistance (AMR) is a major global public health challenge. In addition to antibiotic selection pressure, insecticides have attracted increasing attention as widely used non-antibiotic chemicals that may contribute to the emergence and dissemination of bacterial resistance in the environment. This review focused on common insecticides, including organophosphorus insecticides, pyrethroids, and neonicotinoids, and summarized current evidence on their effects on the emergence of AMR, and the spread of antibiotic resistance genes (ARGs). Existing studies suggest that exposure to certain insecticides may reduce bacterial susceptibility to antibiotics and is associated with the proliferation of antibiotic-resistant bacteria, enrichment of ARGs, co-enrichment of mobile genetic elements (MGEs), and enhanced horizontal gene transfer. Potential mechanisms include changes in antibiotic target-related pathways, decreased membrane permeability, activation of efflux pumps, and enzymatic modification or degradation of antibiotics. The dissemination of ARGs may also be promoted through reactive oxygen species (ROS) accumulation, activation of the SOS response, altered cell membrane permeability, changes in extracellular polymeric substance (EPS) synthesis, altered energy metabolism, and regulation of transfer-related genes. Overall, insecticides may act as non-antibiotic selective pressures involved in the evolution and dissemination of bacterial resistance. However, current evidence is still largely derived from laboratory exposure experiments and cross-sectional investigations, and differences among compounds, and long-term risks under real environmental conditions require further clarified. This review may help improve understanding of the environmental health implications of insecticide-associated bacterial resistance and inform risk assessment and prevention strategies for AMR in environmental settings.

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

Objective:To investigate the expression of long noncoding RNA (lncRNA) BMPR1B-AS1 in ovarian cancer and its impact on prognosis, so as to evaluate its value as a potential biomarker.Methods:The TCGA, GEPIA, and UALCAN databases were used to retrospectively analyze the expression differences of BMPR1B-AS1 in gynecological tumors, and prognostic analysis was performed in combination with clinical data. The expression level of BMPR1B-AS1 in ovarian cancer tissues and cell lines was verified by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR), and univariate and multivariate Cox regression models were used to analyze its relationship with the prognosis of ovarian cancer.Results:Database analysis showed that the expression of BMPR1B-AS1 in ovarian cancer and endometrial cancer was higher than that in the non-tumor group (all P<0.05), and high expression of BMPR1B-AS1 in ovarian cancer was associated with better prognosis ( P<0.05). Experimental verification showed that the expression of BMPR1B-AS1 in ovarian cancer tissues was significantly higher than that in benign ovarian tissues, and the expression of BMPR1B-AS1 in ovarian cancer cell lines was higher than that in normal human ovarian epithelial cells ( P<0.05). Cox regression analysis indicated that high expression of BMPR1B-AS1 was an independent protective factor for the prognosis of ovarian cancer ( P<0.05). Conclusions:The expression of BMPR1B-AS1 in ovarian cancer and endometrial cancer is higher than that in non-tumor groups, and it is an independent protective factor for good prognosis in ovarian cancer patients. It may serve as a new biomarker, providing new ideas for the diagnosis and treatment of ovarian cancer.

Paradoxical psoriasis is a special adverse drug reaction characterized by the new onset, exacerbation, or phenotypic change of psoriatic lesions during treatment with biological agents. In recent years, with the increasing use of biologics, this condition has garnered growing attention from clinicians. The pathogenesis of paradoxical psoriasis is complex and its clinical manifestations are highly heterogeneous. Diagnosis currently relies primarily on clinical features and medication history due to the lack of unified diagnostic criteria. Furthermore, treatment strategies—such as whether to discontinue the original biologic agent or switch therapies—remain controversial, posing significant challenges in clinical management.This article presents a case of paradoxical psoriasis occurring in a patient with ankylosing spondylitis following treatment with the tumor necrosis factor-α inhibitor (TNFi) infliximab. By discussing the clinical characteristics of this case, we aim to enhance clinicians' understanding of this condition, reduce misdiagnosis and underdiagnosis, and provide valuable insights for its diagnosis and treatment.

Objective To investigate the effect of subanesthetic dose of esketamine on emergence agitation(EA)in patients undergoing laparoscopic hernia repair.Methods Seventy-two male patients who treated with lapa-roscopic hernia repair under general anesthesia were randomly divided into AS group(subanesthetic esketamine)and control group.In the AS group,0.2 mg/kg of esketamine was administered intravenously 30 minutes before the surgery ended,while the control group was given an equal volume of normal saline.Upon surgery completion,patients were transferred to PACU with endotracheal tube retained,and the time to extubation was recorded.Hemo-dynamic parameters were measured immediately after extubation and at 10 min,30 min,1 h,and 4 h thereafter.Patients' pain and sedation levels were assessed at the above time points using RASS and VAS,respectively.The incidence of EA was evaluated using the Confusion Assessment Method for the Intensive Care Unit(CAM-ICU).Observation duration in the PACU and recovery outcomes within 24 hours postoperatively were assessed via the QoR-40 and adverse events were recorded.Results Compared to those in the control group,patients in the AS group had higher HR and MAP at 10 min post-extubation,and the changes in HR and MAP over time were more stable(P<0.05).The RASS and VAS scores in the AS group were significantly lower than those in the control group at the time of extubation and all subsequent time points(P<0.05),both groups showed temporal changes in RASS and VAS scores(P<0.05),but the change process in the AS group was more stable(P<0.05).Postoperative extubation time,PACU observation duration,and adverse event rates(delirium,respiratory depression,nausea and vomiting)did not differ significantly between the two groups(P>0.05),while recovery quality was markedly better in the AS group(P<0.05).Conclusion Subanesthetic esketamine effectively alleviates pain and the incidence of EA,supports hemodynamic stability during PACU stay,and enhances recovery quality in patients undergoing laparo-scopic hernia repair,demonstrating clinical value.

Objective:To investigate the causal relationships between multiple obesity indices, including body mass index (BMI), body fat percentage, whole-body fat mass, trunk fat mass, leg fat percentage, arm fat percentage, waist circumference, and hip circumference, and preeclampsia (PE) using Mendelian randomization (MR), and to evaluate the mediating effect of triglycerides.Methods:Genome-wide association studies (GWAS) summary statistics from European populations were utilized. Independent genetic loci associated with obesity indices and PE served as instrumental variables of exposure and outcomes. Obesity data (approximately 191 000 female samples) came from UK Biobank; PE data ( n=242 852) from FinnGen Biobank. Causal effects were assessed primarily via inverse variance weighted (IVW), supplemented by MR-Egger, weighted median, MR-pleiotropy residual sum and outlier (MR-PRESSO), and Bayesian weighted MR. Bonferroni correction was applied. Cochran's Q test evaluated heterogeneity; MR-Egger intercept test assessed horizontal pleiotropy; leave-one-out, funnel, and scatter plots conducted sensitivity analyses. Odds ratio ( OR) measured effect sizes. Two-step MR explored triglyceride mediation. Results:Eighty-two to 112 single nucleotide polymorphisms were included as instrumental variables. After Bonferroni correction, significant positive causal associations with PE were observed for: BMI (IVW: OR=1.703, 95% CI: 1.469-1.974, P<0.001), body fat percentage (IVW: OR=1.595, 95% CI: 1.321-1.925, P<0.001), whole-body fat mass (IVW: OR=1.639, 95% CI: 1.389-1.934, P<0.001), right leg fat percentage (IVW: OR=1.610, 95% CI: 1.360-1.905, P<0.001), left leg fat percentage (IVW: OR=1.622, 95% CI: 1.363-1.930, P<0.001), right arm fat percentage (IVW: OR=1.591, 95% CI: 1.351-1.872, P<0.001), left arm fat percentage (IVW: OR=1.710, 95% CI: 1.444-2.024, P<0.001), and waist circumference (IVW: OR=1.815, 95% CI: 1.534-2.148, P<0.001). Sensitivity analyses confirmed robustness. Triglycerides mediated 4.6%-8.2% of these effects. Trunk fat mass and hip circumference showed potential positive associations (IVW: OR>1, 0.005≤ P<0.05). Conclusions:Higher BMI, body fat percentage, whole-body fat mass, leg/arm fat percentages, and waist circumference may increase PE risk, with waist circumference showing the strongest association. These effects may be partially mediated by triglycerides.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To investigate the effect of brinzolamide-timolol maleate eye drops on the metabolism of intravitreally injected vancomycin hydrochloride (VH) in rabbit eyes.Methods:Nine healthy male New Zealand white rabbits were selected.Among them, three were used to extract blank aqueous humor and the right eyes of the remaining six were set as experimental eyes.The experimental eye was topically administered 30 μl of brinzolamide-timolol maleate eye drops twice a day.The fellow eyes were set as control eyes.The intraocular pressure of both eyes was measured before the initial application of the eye drops and 1 hour after application of the eye drops next day.Both eyes of each rabbit were intravitreally injected with 0.5 mg of VH (10 mg/ml) solution.The aqueous humor was drawn at 2 hours and 1, 2, 4, 6, 8, 10 and 12 days after intravitreal injection.VH concentrations in aqueous humor were measured by high performance liquid chromatography.The time of peak concentrations ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and the area under the concentration-time curve ( AUC) of VH in rabbit eyes were calculated by the average concentrations.This study was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-01). Results:The intraocular pressure after eye drop was significantly lower than that before eye drop in experimental eyes ( P<0.01).The tmax of VH in experimental eyes and control eyes were both 1 day.The Cmax of VH in experimental eyes and control eyes were (61.40±13.48) and (51.56±5.07)μg/ml, respectively.The VH aqueous concentrations in the experimental eyes on days 4, 6 and 8 after injection were all significantly higher than those in the control eye ( t=2.378, 3.150, 2.694; all P<0.05).The t1/2 of VH in the aqueous humor of the experimental eyes was 2.69 days, which was 31% longer than 2.05 days of the control eyes.The AUC0-10 d of experimental eyes increased by 24.3% relative to the control eyes. Conclusions:Brinzolamide-timolol maleate eye drops can significantly extend the ocular residence time of intravitreally injected VH.

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

The neuropsychiatric disorder course is among the most challenging subjects in medical education, currently facing the "three difficulties" of teaching, learning, and transition from theory to practice. This study attempts to carry out clinical thinking informatization technology-based teaching reform guided by clinical competence. A cognitive map for neuropsychiatric disorders was developed using a symptom-based framework. Leveraging this cognitive map and integrating artificial intelligence, a clinical thinking teaching application for neuropsychiatric disorders was designed and continuously refined. Reform initiatives were explored and summarized in areas such as theoretical teaching, practical teaching, standardized training for resident physicians, teaching assessment, and textbook reform. The reform improved the clinical thinking and clinical competence of students for neuropsychiatric disorders.