Objective:To compare the efficacy of anrikefon and tegileridine for analgesia in patients with moderate-to-severe pain after abdominal surgery with general anesthesia.Methods:In this multicenter, randomized, double-blind, active-controlled clinical trial, 101 patients with moderate to severe pain (numeric pain rating scale [NRS] score ≥4 within 4 h after operation) after abdominal surgery with general anesthesia between February 24 and April 1, 2025, aged 18-70 yr, with a body mass index of 18-40 kg/m 2, were assigned to anrikefon group ( n=50) and tegileridine group ( n=51) in a 1∶1 ratio using stratified blocked randomization. Double-dummy design was employed to maintain blinding. Each group received an initial intravenous injection of anrikefon 1 μg/kg or tegileridine 1 mg, followed by connection to a patient-controlled intravenous analgesia (PCIA) pump (the PCIA solution contained normal saline in anrikefon group; the PCIA solution contained tegileridine 5 mg in tegileridine pump) within 10 min. If the patient′s NRS score ≥4 at 8 and 16 h after the initial injection, anrikefon 1 μg/kg was intravenously injected in anrikefon group, and tegileridine group received the equal volume of normal saline. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 24 h after the initial dose (SPID 0-24h). The secondary efficacy endpoints included the incidence and severity of vomiting and nausea, incidence of postoperative nausea and vomiting(PONV), the proportion of patients who received antiemetic treatment, and total consumption of antiemetics within 0-24 h after the initial dose, NRS score at rest ≤ 1 at 24 h after the initial dose, and NRS score at rest ≤ 3 over the first 24 h after the initial dose. Safety indicators included adverse events, vital signs, physical examination findings, 12-lead ECG and laboratory test indicators, and adverse events of special interest. Results:Compared with tegileridine group, no significant change was found in the SPID 0-24h ( P>0.05), and the incidence of vomiting, PONV, proportion of patients requiring antiemetic medication, and total consumption of antiemetics were significantly decreased within the first 24 h after the initial dose in tegileridine group ( P<0.05). One treatment-emergent adverse event of Common Terminology Criteria for Adverse Events grade 3 or higher occurred in tegileridine group, while no treatment-emergent adverse events of Common Terminology Criteria for Adverse Events grade 3 or higher were found in anrikefon group. Among the adverse events of special interest, one case of respiratory depression and one case of cough occurred in tegileridine group, while one case of cough occurred in anrikefon group, with no respiratory depression. Conclusions:Anrikefon and tegileridine provide comparable analgesic efficacy for moderate-to-severe pain after abdominal surgery with general anesthesia. However, anrikefon exhibits an advantage in reducing the risk of PONV, with a superior safety profile.

Objective:To investigate the clinical distribution characteristics changes in antimicrobial resistance, and carbapenemase resistance genes of Klebsiella pneumoniae isolated from children in Chongqing region during the period of January 2019 to December 2024, providing a basis for the rational use of antibiotics and the prevention and control of nosocomial infections.Methods:An observational study was conducted to retrospectively analyze 5 020 Klebsiella pneumoniae (KP) isolates detected in four hospitals of the Southwest Pediatric Laboratory Specialty Alliance. Antimicrobial susceptibility testing was performed by the minimum inhibitory concentration method combined with the disk diffusion method. Results were interpreted according to the 2024 Clinical and Laboratory Standards Institute (CLSI) standards. Carbapenemase resistance genes were detected by polymerase chain reaction (PCR) combined with Sanger sequencing. WHONET 5.6 was used for resistance analysis and SPSS 19.0 for statistical analysis. The chi-square test was used to assess trends in resistance rates, ESBL detection rates, and resistance rates of different CRKP carbapenemase genotypes from 2019 to 2024. Statistical significance was confirmed if the two-tailed P-value was <0.05. Results:A total of 5 020 strains were isolated, with a detection rate of 5.1% (5 020/99 063). The majority were from sputum (59.2%, 2 970/5 020), followed by pus (17.1%, 857), urine (9.7%, 487), venous blood (6.5%, 326), secretions (2.6%, 130), and other specimens (5.0%, 250).The lowest resistance rate was to amikacin (3.8%), followed by levofloxacin (10.9%), imipenem (19.1%), and meropenem (19.9%). Resistance rates to cefoperazone/sulbactam ( χ2=9.982 0, P=0.001 6), piperacillin/tazobactam ( χ2=10.110 0, P=0.001 5), ceftazidime ( χ2=3.849 0, P=0.049 8), cefotaxime ( χ2=7.605 0, P=0.005 8), cefepime ( χ2=13.510 0, P=0.000 2), aztreonam ( χ2=6.457 0, P=0.011 1), imipenem ( χ2=4.672 0, P=0.030 7), and levofloxacin ( χ2=7.555 0, P=0.006 0) showed an annual increasing trend. The main carbapenemase genes were blaNDM-5 (42.2%, 127/301), blaNDM-1 (33.9%, 102/301), and blaKPC-2 (17.3%, 52/301). Patients with KPC-2-producing strains (median age, 240 days) were older than those with NDM-1/NDM-5-producing strains (median age, 40 days) ( χ2=22.620 0, P<0.000 1). In neonatal wards, the detection rate of NDM-KP was higher than that of KPC-KP (64.6%, 148/229 vs. 26.9%, 14/52, χ2=24.680 0, P<0.000 1), whereas in ICUs, it was lower (6.1%, 14/229 vs. 26.9%, 14/52, χ2=20.450 0, P<0.000 1). Conclusion:In Chongqing region, the isolation rate of K. pneumoniae from sputum was the highest with most cases from neonatal wards. Resistance to carbapenems showed an upward trend. BlaNDM-5 was the predominant genotype in pediatric CRKP. Patients with KPC-KP were older than those with NDM-KP. NDM-KP predominated in neonatal wards, while KPC-KP predominated in ICUs, with KPC-KP showing higher antimicrobial resistance.

Objective Text mining of content characteristics of original science popularization articles on the WeChat public account"PSM Medicine Shield Public Welfare"based on LDA model and Linear Regression.Methods Through web crawling techniques,we collected 4,292 original pharmaceutical science popularization articles and associated comment data from the"PSM Drug Shield Public Welfare"WeChat Official Account to analyze the content distribution patterns and characteristics of pharmaceutical science communication.Employing Latent Dirichlet Allocation(LDA)modeling,we systematically categorized and mined article themes to identify public demand for science literacy and explore strategic directions for precision-targeted phar-maceutical science dissemination.Results The analysis of 4 292 original science popularization articles from the"PSM Medi-cine Shield Public Welfare"account showed an average readership of 1 815.73±4 385.31.Articles in headline positions,pub-lished on weekends,or using exclamatory titles achieved higher readership.Most articles(1 000-2 000 words)used direct-open-ing title strategies.Traditional Chinese medicines had the highest readership among drug categories.Top content categories in-cluded drug monographs,medicinal diets,disease medication guidance,myth clarification,and disease science.Linear regres-sion analysis identified headline placement,word count,title phrasing,title strategy,target audience,drug category,and content type as potential factors influencing readership.The LDA model with 9 s revealed key themes:management of drug adverse reac-tions,dermatological medication dosing,anti-infection effects of medicinal diets,and pediatric vaccination/health monitoring.Conclusion The"PSM Medicine Shield Public Welfare"WeChat account primarily disseminates pharmaceutical science content focusing on adverse drug reactions,pediatric medication safety,TCM-based health preservation,disease treatment protocols,symptom recognition guidelines,dosage optimization,and toxicity management.Pharmaceutical professionals should prioritize content length control,evidence-based title strategies,and thematic alignment with public health priorities during science commu-nication content creation.

Objective Text mining of content characteristics of original science popularization articles on the WeChat public account"PSM Medicine Shield Public Welfare"based on LDA model and Linear Regression.Methods Through web crawling techniques,we collected 4,292 original pharmaceutical science popularization articles and associated comment data from the"PSM Drug Shield Public Welfare"WeChat Official Account to analyze the content distribution patterns and characteristics of pharmaceutical science communication.Employing Latent Dirichlet Allocation(LDA)modeling,we systematically categorized and mined article themes to identify public demand for science literacy and explore strategic directions for precision-targeted phar-maceutical science dissemination.Results The analysis of 4 292 original science popularization articles from the"PSM Medi-cine Shield Public Welfare"account showed an average readership of 1 815.73±4 385.31.Articles in headline positions,pub-lished on weekends,or using exclamatory titles achieved higher readership.Most articles(1 000-2 000 words)used direct-open-ing title strategies.Traditional Chinese medicines had the highest readership among drug categories.Top content categories in-cluded drug monographs,medicinal diets,disease medication guidance,myth clarification,and disease science.Linear regres-sion analysis identified headline placement,word count,title phrasing,title strategy,target audience,drug category,and content type as potential factors influencing readership.The LDA model with 9 s revealed key themes:management of drug adverse reac-tions,dermatological medication dosing,anti-infection effects of medicinal diets,and pediatric vaccination/health monitoring.Conclusion The"PSM Medicine Shield Public Welfare"WeChat account primarily disseminates pharmaceutical science content focusing on adverse drug reactions,pediatric medication safety,TCM-based health preservation,disease treatment protocols,symptom recognition guidelines,dosage optimization,and toxicity management.Pharmaceutical professionals should prioritize content length control,evidence-based title strategies,and thematic alignment with public health priorities during science commu-nication content creation.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective:To compare the efficacy of anrikefon and tegileridine for analgesia in patients with moderate-to-severe pain after abdominal surgery with general anesthesia.Methods:In this multicenter, randomized, double-blind, active-controlled clinical trial, 101 patients with moderate to severe pain (numeric pain rating scale [NRS] score ≥4 within 4 h after operation) after abdominal surgery with general anesthesia between February 24 and April 1, 2025, aged 18-70 yr, with a body mass index of 18-40 kg/m 2, were assigned to anrikefon group ( n=50) and tegileridine group ( n=51) in a 1∶1 ratio using stratified blocked randomization. Double-dummy design was employed to maintain blinding. Each group received an initial intravenous injection of anrikefon 1 μg/kg or tegileridine 1 mg, followed by connection to a patient-controlled intravenous analgesia (PCIA) pump (the PCIA solution contained normal saline in anrikefon group; the PCIA solution contained tegileridine 5 mg in tegileridine pump) within 10 min. If the patient′s NRS score ≥4 at 8 and 16 h after the initial injection, anrikefon 1 μg/kg was intravenously injected in anrikefon group, and tegileridine group received the equal volume of normal saline. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 24 h after the initial dose (SPID 0-24h). The secondary efficacy endpoints included the incidence and severity of vomiting and nausea, incidence of postoperative nausea and vomiting(PONV), the proportion of patients who received antiemetic treatment, and total consumption of antiemetics within 0-24 h after the initial dose, NRS score at rest ≤ 1 at 24 h after the initial dose, and NRS score at rest ≤ 3 over the first 24 h after the initial dose. Safety indicators included adverse events, vital signs, physical examination findings, 12-lead ECG and laboratory test indicators, and adverse events of special interest. Results:Compared with tegileridine group, no significant change was found in the SPID 0-24h ( P>0.05), and the incidence of vomiting, PONV, proportion of patients requiring antiemetic medication, and total consumption of antiemetics were significantly decreased within the first 24 h after the initial dose in tegileridine group ( P<0.05). One treatment-emergent adverse event of Common Terminology Criteria for Adverse Events grade 3 or higher occurred in tegileridine group, while no treatment-emergent adverse events of Common Terminology Criteria for Adverse Events grade 3 or higher were found in anrikefon group. Among the adverse events of special interest, one case of respiratory depression and one case of cough occurred in tegileridine group, while one case of cough occurred in anrikefon group, with no respiratory depression. Conclusions:Anrikefon and tegileridine provide comparable analgesic efficacy for moderate-to-severe pain after abdominal surgery with general anesthesia. However, anrikefon exhibits an advantage in reducing the risk of PONV, with a superior safety profile.

Objective:To investigate the clinical distribution characteristics changes in antimicrobial resistance, and carbapenemase resistance genes of Klebsiella pneumoniae isolated from children in Chongqing region during the period of January 2019 to December 2024, providing a basis for the rational use of antibiotics and the prevention and control of nosocomial infections.Methods:An observational study was conducted to retrospectively analyze 5 020 Klebsiella pneumoniae (KP) isolates detected in four hospitals of the Southwest Pediatric Laboratory Specialty Alliance. Antimicrobial susceptibility testing was performed by the minimum inhibitory concentration method combined with the disk diffusion method. Results were interpreted according to the 2024 Clinical and Laboratory Standards Institute (CLSI) standards. Carbapenemase resistance genes were detected by polymerase chain reaction (PCR) combined with Sanger sequencing. WHONET 5.6 was used for resistance analysis and SPSS 19.0 for statistical analysis. The chi-square test was used to assess trends in resistance rates, ESBL detection rates, and resistance rates of different CRKP carbapenemase genotypes from 2019 to 2024. Statistical significance was confirmed if the two-tailed P-value was <0.05. Results:A total of 5 020 strains were isolated, with a detection rate of 5.1% (5 020/99 063). The majority were from sputum (59.2%, 2 970/5 020), followed by pus (17.1%, 857), urine (9.7%, 487), venous blood (6.5%, 326), secretions (2.6%, 130), and other specimens (5.0%, 250).The lowest resistance rate was to amikacin (3.8%), followed by levofloxacin (10.9%), imipenem (19.1%), and meropenem (19.9%). Resistance rates to cefoperazone/sulbactam ( χ2=9.982 0, P=0.001 6), piperacillin/tazobactam ( χ2=10.110 0, P=0.001 5), ceftazidime ( χ2=3.849 0, P=0.049 8), cefotaxime ( χ2=7.605 0, P=0.005 8), cefepime ( χ2=13.510 0, P=0.000 2), aztreonam ( χ2=6.457 0, P=0.011 1), imipenem ( χ2=4.672 0, P=0.030 7), and levofloxacin ( χ2=7.555 0, P=0.006 0) showed an annual increasing trend. The main carbapenemase genes were blaNDM-5 (42.2%, 127/301), blaNDM-1 (33.9%, 102/301), and blaKPC-2 (17.3%, 52/301). Patients with KPC-2-producing strains (median age, 240 days) were older than those with NDM-1/NDM-5-producing strains (median age, 40 days) ( χ2=22.620 0, P<0.000 1). In neonatal wards, the detection rate of NDM-KP was higher than that of KPC-KP (64.6%, 148/229 vs. 26.9%, 14/52, χ2=24.680 0, P<0.000 1), whereas in ICUs, it was lower (6.1%, 14/229 vs. 26.9%, 14/52, χ2=20.450 0, P<0.000 1). Conclusion:In Chongqing region, the isolation rate of K. pneumoniae from sputum was the highest with most cases from neonatal wards. Resistance to carbapenems showed an upward trend. BlaNDM-5 was the predominant genotype in pediatric CRKP. Patients with KPC-KP were older than those with NDM-KP. NDM-KP predominated in neonatal wards, while KPC-KP predominated in ICUs, with KPC-KP showing higher antimicrobial resistance.

Objective:Comparison of the U. S. Food and Drug Administration (FDA) Protocol Deviations for Clinical Investigation of Drugs, Biological Products, and Devices Guidance for Industry (Draft Guidance) and the Beijing Investigator-Initiated Trial (IIT) Supervision and Inspection Content and Assessment Principles with recommendations for managing protocol deviations in IITs.Methods:A comparative analysis was conducted focusing on the terminology, definitions, classifications, determination criteria, and management requirements for protocol deviations. The analysis was supplemented by practical experience from the 2024 IIT supervision and inspection in Beijing to explore the applicability of the FDA guidance in the local context.Results:The FDA guidance clearly defined the terminology and scope of protocol deviations, distinguishes between important and other deviations, emphasized the principle of quality by design, and clarified the responsibilities of relevant stakeholders and reporting procedures. The Beijing IIT Supervision and Inspection Assessment Principles, for the first time from a government regulatory perspective, introduced a quantitative classification system for determining the severity of protocol deviations. However, they had not fully addressed issues such as participant privacy protection and premature unblinding, and the management requirements remain to be refined. Findings from the 2024 IIT supervision and inspection in Beijing indicate that the most common protocol deviations were failure to follow the protocol-defined schedule or procedures for visits, tests, or outcome assessments; failure to collect critical data; and violations of inclusion/exclusion criteria.Conclusions:While Beijing has made progress in institutionalizing IIT management, the overall protocol deviation management system remains underdeveloped. This paper proposes the following recommendations: First, clearly define the responsibilities of various stakeholders within research institutions, strengthen coordination among administrative departments, ethics committees, and research teams, and fully leverage the support role of the Beijing Center for Advancing Quality in Clinical Research in methodological guidance and quality control. Second, enhance the capacity and ongoing training of research teams, and encourage medical institutions to provide methodological consultation and technical support. Third, improve the scientific rigor and feasibility of protocol design by tailoring inclusion/exclusion criteria and follow-up strategies to the specific study type and target population, optimizing study procedures, and developing risk-based management plans. Fourth, refine the classification criteria, reporting procedures, and timelines for protocol deviations, and implement a tiered management system based on the nature and severity of the deviation.