OBJECTIVE To investigate the efficacy and safety of omadacycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia （MUMPP） in children. METHODS A retrospective study was conducted on children aged 1-18 years old with MUMPP who were hospitalized in the Department of Pediatrics， the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2025. According to the selection of secondary antibiotics after 72 h of initial treatment with macrolides， they were divided into the omadacycline group and the doxycycline group. Based on conventional treatment， children in the omadacycline group were given intravenous infusion of 2.4 mg/kg （once daily） of omadacycline tosylate， while children in the doxycycline group were given oral doxycycline hydrochloride tablets at 2 mg/kg （twice daily）. The efficacy and safety were compared between the two groups of pediatric patients. Univariate analysis and multivariate Logistic regression analysis were performed on clinical efficacy， and subgroup analysis along with multiple sensitivity analyses were conducted to verify the robustness of the conclusions. RESULTS A total of 284 children with MUMPP were included in this study， with 142 in the omadacycline group and 142 in the doxycycline group. In terms of efficacy， although the hospitalization time of children in the omadacycline group was longer than that in the doxycycline group （ P ＜0.05）， the lung lesion absorption rate and clinical efficacy were significantly higher or better than those in the doxycycline group （ P ＜0.05）. The results of multivariate Logistic regression analysis showed that medication （OR＝5.300， 95%CI： 2.526-11.123）， length of hospital stay （OR＝1.348， 95%CI： 1.167-1.556）， and medication duration （OR＝1.422， 95%CI： 1.169-1.729） were influencing factors of clinical efficacy （ P ＜0.05）. The subgroup analysis results showed that the clinical efficacy of omadacycline was significantly better than that of doxycycline in all subgroups （ P ＜0.05）. The results of multiple sensitivity analysis showed that the regression coefficients B of the four models （gradually adjust variables） before and after inverse probability of treatment weighting were significantly greater than 1 （ P ＜0.05）. In terms of safety， there was no statistically significant difference in the inci dence of adverse drug reactions between the two groups of patients （ χ 2 ＝0.447， P ＝0.504）. CONCLUSIONS In the case of hospitalization and prolonged medication， the efficacy of omadacycline in treating childhood MUMPP is superior to that of doxycycline， and its safety is good.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Mannheimia varigena(M.varigena)is a significant pathogen causing bovine respiratory disease.Transferrin binding protein B(TbpB)is a lipoprotein directly exposed to the outer mem-brane of the cell,which is not only involved in the bacterial iron metabolism pathway,but also an important virulence factor.This study aims to lay the groundwork for developing novel subunit vaccines by conducting site-directed mutagenesis on M.varigena TbpB binding-related residues and evaluating their immunogenicity.Based on whole-genome sequencing of a bovine M.varigena i-solate,its iron uptake pathway was predicted.Key amino acid residues of M.varigena TbpB that play a role for binding to bovine transferrin(bTf)was identified by bioinformatics.We constructed two M.varigena TbpB mutants(Y205A and Y258A)and assessed their bTf binding activity and immunogenicity through dot blot assays and mouse immunization studies.Dot blot assays result showed that the Y258A mutation caused TbpB to lose its ability to bind to bTf.Mouse immuniza-tion studies showed that,compared to wild-type TbpB,the mutants of TbpB induced higher levels of specific antibodies.In challenge experiments,mice immunized with mutant TbpB exhibited high-er survival rates.These results demonstrate that site-directed mutagenesis can enhance the immu-nogenicity of TbpB.This study provides a novel approach for developing new subunit vaccines a-gainst M.varigena.

Objective:To explore the correlation between levels of serum cold-inducible RNA-binding protein(CIRBP), cystatin C(CysC) and cognitive impairment in patients with cerebral small vessel disease(CSVD), as well as the diagnostic value of CI in CSVD.Methods:A total of 90 CSVD patients admitted to the Neurology Department of Zhengzhou People's Hospital from January 2024 to December 2024 were consecutively selected. According to the mini-mental state examination(MMSE) and Montreal cognitive assessment(MoCA), they were divided into non cognitive impairment group(NCI group, n=47) and cognitive impairment group(CI group, n=43). The general clinical data of patients were collected.Fasting venous blood was collected in the morning on the second day of admission to measure serum CIRBP, CysC, homocysteine(Hcy) and high-sentivity C-reactive protein(hs-CRP) levels.A multiple-factor Logistic regression model was applied to identify independent risk factors for CI in CSVD patients, the predictive performance of the model was evaluated by receiver operating characteristic(ROC) curves, and the area under the curve(AUC) value was calculated to quantify the diagnostic accuracy of the model. Results:The levels of Hcy((13.01±4.22)μmol/L vs (11.44±3.00)μmol/L), hs-CRP((2.84±3.01)mmol/L vs (1.81±1.32)mmol/L), CIRBP((2 412.40±967.78)pg/mL vs (1 715.13±971.98)pg/mL), and CysC((1.93±1.08)mg/L vs (1.24±0.87)mg/L) in the CI group were significantly higher than those in the NCI group(all P<0.05). Multiple Logistic regression analysis showed that both CIRBP( OR=1.001, 95% CI=>1.000-1.002, P=0.011) and CysC( OR=1.833, 95% CI=1.056-3.181, P=0.031) were independently influencing factors of the occurrence of CI in CSVD patients(all P<0.05). ROC curve analysis showed that the optimal cutoff values for serum CIRBP and CysC levels to evaluate CI were 1 875.50 pg/mL and 1.42 mg/L, respectively. The AUC (95% CI) were 0.805(95% CI=0.713-0.897, P<0.001) and 0.716(95% CI=0.607-0.825, P<0.001), respectively.The AUC(95% CI) of combined detection of CIRBP+ CysC was 0.820(95% CI=0.733-0.907, P<0.001), with specificity and sensitivity of 89.4% and 67.4%. Conclusion:The serum CIRBP and CysC levels can serve as independent predictors of CI in CSVD patients. Combined testing can improve the accuracy of patient condition assessment and may assist in the diagnosis and prediction of cognitive impairment in CSVD.

Objective:To explore the correlation between levels of serum cold-inducible RNA-binding protein(CIRBP), cystatin C(CysC) and cognitive impairment in patients with cerebral small vessel disease(CSVD), as well as the diagnostic value of CI in CSVD.Methods:A total of 90 CSVD patients admitted to the Neurology Department of Zhengzhou People's Hospital from January 2024 to December 2024 were consecutively selected. According to the mini-mental state examination(MMSE) and Montreal cognitive assessment(MoCA), they were divided into non cognitive impairment group(NCI group, n=47) and cognitive impairment group(CI group, n=43). The general clinical data of patients were collected.Fasting venous blood was collected in the morning on the second day of admission to measure serum CIRBP, CysC, homocysteine(Hcy) and high-sentivity C-reactive protein(hs-CRP) levels.A multiple-factor Logistic regression model was applied to identify independent risk factors for CI in CSVD patients, the predictive performance of the model was evaluated by receiver operating characteristic(ROC) curves, and the area under the curve(AUC) value was calculated to quantify the diagnostic accuracy of the model. Results:The levels of Hcy((13.01±4.22)μmol/L vs (11.44±3.00)μmol/L), hs-CRP((2.84±3.01)mmol/L vs (1.81±1.32)mmol/L), CIRBP((2 412.40±967.78)pg/mL vs (1 715.13±971.98)pg/mL), and CysC((1.93±1.08)mg/L vs (1.24±0.87)mg/L) in the CI group were significantly higher than those in the NCI group(all P<0.05). Multiple Logistic regression analysis showed that both CIRBP( OR=1.001, 95% CI=>1.000-1.002, P=0.011) and CysC( OR=1.833, 95% CI=1.056-3.181, P=0.031) were independently influencing factors of the occurrence of CI in CSVD patients(all P<0.05). ROC curve analysis showed that the optimal cutoff values for serum CIRBP and CysC levels to evaluate CI were 1 875.50 pg/mL and 1.42 mg/L, respectively. The AUC (95% CI) were 0.805(95% CI=0.713-0.897, P<0.001) and 0.716(95% CI=0.607-0.825, P<0.001), respectively.The AUC(95% CI) of combined detection of CIRBP+ CysC was 0.820(95% CI=0.733-0.907, P<0.001), with specificity and sensitivity of 89.4% and 67.4%. Conclusion:The serum CIRBP and CysC levels can serve as independent predictors of CI in CSVD patients. Combined testing can improve the accuracy of patient condition assessment and may assist in the diagnosis and prediction of cognitive impairment in CSVD.

Objective:To evaluate the efficacy of rhomboid inter-costal and sub-serratus (RISS) block with ropivacaine-dexmedetomidine-dexamethasone for analgesia after thoracoscopic lobectomy.Methods:This study was a prospective, randomized, double-blind, controlled trial. From January 2021 to November 2023, 46 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, undergoing elective video-assisted thoracoscopic lobectomy at the Second Affiliated Hospital of Nanjing Medical University, were selected and assigned into 2 groups ( n=23 each) using simple randomization: ropivacaine group (R group) and ropivacaine-dexmedetomidine-dexamethasone group (RDA group). RISS block was performed preoperatively, with 20 ml of the drug solution injected at the target points of the rhomboid-intercostal muscle and the serratus anterior-intercostal muscle. R group received 0.375% ropivacaine 40 ml, while RDA group received 40 ml of the mixture containing 0.375% ropivacaine, dexmedetomidine 1 μg/kg, and dexamethasone 8 mg. Postoperative analgesia was performed with oxycodone (When the patient′s numerical rating scale [NRS] score >4 in post-anesthesion care unit, oxycodone 2 mg was intravenously administered as needed until the NRS score <4, and then a patient-controlled analgesia pump was initiated). The time of the first postoperative analgesic requirement, NRS scores at rest and during coughing at 1, 3, 6, 12, 24 and 48 h postoperatively, cumulative consumption of oxycodone in the periods of 0-12 h, >12-24 h, and >24-48 h, time to first ambulation, and incidence of related adverse reactions within 48 h postoperatively were recorded. Results:Compared with R group, the time to the first analgesic requirement was significantly prolonged, the cumulative consumption of oxycodone in the first 0-12 h postoperatively was reduced ( P<0.001), and no statistically significant changes were found in the time to first ambulation, NRS scores at rest and during coughing, or the incidence of postoperative adverse reactions in RDA group ( P>0.05). Conclusions:RISS block using a combination of ropivacaine, dexmedetomidine and dexamethasone can significantly prolong block duration, reduce postoperative opioid analgesic consumption, and provide good safety for the patients undergoing thoracoscopic lobectomy.

Objective:To determine the median effective dose (ED 50) of oliceridine inhibiting the responses to the laryngeal mask airway insertion when combined with ciprofol in elderly patients. Methods:In this sequential trial, American Society of Anesthesiologists Physical Status classificationⅠ-Ⅲ elderly patients of either sex, aged ≥65 yr, with a body mass index of 18-30 kg/m 2, undergoing elective urological surgery under general anesthesia with laryngeal mask airway, were included in this study. Ciprofol 0.4 mg/kg was intravenously injected, the dose of oliceridine was determined by using modified Dixon′s up-and-down method (increment or decrement of 0.005 mg/kg), and the initial dose of oliceridine was 0.01 mg/kg. A positive response was defined as an increase in maximum mean arterial pressure or heart rate ≥20% within 3 min after inserting the laryngeal mask airway or occurrence of any one of these signs such as movement, coughing, frowning, mouth corner twitching, tearing, laryngospasm, or bispectral index value failing to drop below 60. The trial was terminated upon observing 7 positive-to-negative transition points, starting from the first occurrence of an alternation between positive and negative responses to laryngeal mask airway insertion. The ED 50 and 95% confidence interval of oliceridine inhibiting the responses to the laryngeal mask airway insertion was calculated when combined with ciprofol in elderly patients. Results:The ED 50 of oliceridine inhibiting the response to laryngeal mask airway insertion was 0.027 mg/kg, and the 95% confidence interval was 0.008-0.048 mg/kg when combined with ciprofol 0.4 mg/kg. Conclusions:The ED 50 of oliceridine inhibiting the response to laryngeal mask airway insertion is 0.027 mg/kg when combined with ciprofol 0.4 mg/kg in elderly patients.

Objective:To analyze the correlation between serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) and risk of all-cause death or cardiovascular disease (CVD) death among urban and rural elderly in Beijing.Methods:Based on the Beijing Healthy Aging Cohort Study, 9 022 participants with complete baseline data were enrolled, and their survival and death outcomes were followed up. Multivariable Cox proportional hazard regression model were used to analyze the associations between the UHR level and the risks of all-cause mortality and CVD mortality.Results:As of March 31, 2021, the median follow-up time M( Q1, Q3) was 6.18 (5.36, 6.75) years. There were 1 166 all-deaths, with a death density of 19.26 per 1 000 person-years, and 562 CVD deaths, with a death density of 9.28 per 1 000 person-years. After adjusting sociodemographic characteristics and lifestyle factors, multivariable Cox proportional hazard regression model showed that the risk of all-cause mortality increased by 3% ( HR=1.03, 95% CI: 1.02-1.04) and the risk of CVD mortality increased by 4% ( HR=1.04, 95% CI: 1.02-1.06) for every 1% increase in UHR. Compared with the T1 group of UHR tertiles, the T3 group had a 42% increase in the risk of all-cause death ( HR=1.42, 95% CI: 1.22-1.66) and a 53% increase in the risk of CVD death ( HR=1.53, 95% CI: 1.21-1.94). Conclusions:The UHR level is significantly associated with the risks of all-cause mortality and CVD mortality among urban and rural older adults in Beijing. The UHR level may be one of the potential predictors of death risk in community-dwelling older adults.

Objective: To identify biomolecular markers closely related to the occurrence of kidney renal clear cell carcinoma (KIRC) and verify their expression levels in clinical samples. Methods: Stage Ⅰ KIRC mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA).Principal component analysis (PCA) was used for dimensionality reduction to screen differentially expressed genes (DEGs)，which then underwent GO and KEGG analyses.Weighted gene co-expression network analysis (WGCNA) was used to screen genes significantly related to KIRC，and a protein-protein interaction (PPI) network was constructed to screen hub genes.The diagnostic value of hub genes was evaluated with receiver operating characteristic (ROC) curve，and their prognostic value was analyzed using survival curve plots.The correlation between the mRNA expressions of hub genes and the pathological stages of KIRC was analyzed.Clinical samples of 20 patients with stage Ⅰ KIRC treated in our hospital were included，and the expressions of the hub genes in cancerous and adjacent tissues were detected with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR)，Western blotting，and enzyme-linked immunosorbent assay (ELISA). Results: A total of 8223 DEGs were screened out，including 4092 up-regulated ones and 4131 down-regulated ones.GO analysis showed that DEGs were related to bioadhesion，plasma membrane composition，and transporter activity.KEGG analysis showed that DEGs were related to pathways such as cell adhesion molecules，cytokine-cytokine receptor interactions，and interactions between viral proteins and cytokines and cytokine receptors.WGCNA analysis obtained 171 genes that were significantly related to stage Ⅰ KIRC.The hub gene，lymphocyte cytosolic protein 2 (LCP2)，screened out by the PPI network，was significantly related to stage Ⅰ KIRC.The area under the ROC curve was 0.96.The expression level was negatively correlated with the overall survival rate of patients.The expression of LCP2 was related to the stage and lymph node metastasis.Clinical verification showed that the mRNA and protein relative expressions of LCP2 in KIRC tissues were significantly higher than those in adjacent tissues (P<0.000 1). Conclusion: LCP2 is significantly up-regulated in stage Ⅰ KIRC tissues and can be used as a potential biomarker for the early diagnosis and treatment of KIRC.

Mannheimia varigena(M.varigena)is a significant pathogen causing bovine respiratory disease.Transferrin binding protein B(TbpB)is a lipoprotein directly exposed to the outer mem-brane of the cell,which is not only involved in the bacterial iron metabolism pathway,but also an important virulence factor.This study aims to lay the groundwork for developing novel subunit vaccines by conducting site-directed mutagenesis on M.varigena TbpB binding-related residues and evaluating their immunogenicity.Based on whole-genome sequencing of a bovine M.varigena i-solate,its iron uptake pathway was predicted.Key amino acid residues of M.varigena TbpB that play a role for binding to bovine transferrin(bTf)was identified by bioinformatics.We constructed two M.varigena TbpB mutants(Y205A and Y258A)and assessed their bTf binding activity and immunogenicity through dot blot assays and mouse immunization studies.Dot blot assays result showed that the Y258A mutation caused TbpB to lose its ability to bind to bTf.Mouse immuniza-tion studies showed that,compared to wild-type TbpB,the mutants of TbpB induced higher levels of specific antibodies.In challenge experiments,mice immunized with mutant TbpB exhibited high-er survival rates.These results demonstrate that site-directed mutagenesis can enhance the immu-nogenicity of TbpB.This study provides a novel approach for developing new subunit vaccines a-gainst M.varigena.