Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective To investigate the effect of nutritional deficiency on autophagic flux in human hepatoblastoma HepG2 cells and the autophagy-dependent molecular pathway mediated by ATG5 against nutritional stress.Methods Lentiviral siRNA knockdown of ATG5 was performed to knock down the expression in HepG2 cells,and the transfection was verified by Western blotting and qRT-PCR.HBSS was used to treat HepG2 cells for 0,1,2,3,4,5,6 and 7 h for starvation-induced autophagy.Monodansylcadaverine(MDC)fluorescence staining was employed to detect the formation of intracellular autophagic vesicles.Western blotting was performed to measure the expression changes in microtubule-associated protein 1A/1B-light chain 3(LC3),autophagy receptor protein(sequestosome 1,P62),autophagy-related gene 5(ATG5)and nutrient stress pathway(AMPK/mTOR pathway)related proteins.CCK-8 assay was utilized to test cell proliferation.Results Compared with the HepG2 cells under conventional culture medium,starvation induction resulted in more autophagic vacuoles(accumulation of autofluorescent marker,MDC),which peaked at 6 h of starvation(P<0.000 1),up-regulated protein levels of LC3B-Ⅱ and ATG5(P<0.05),decreased protein expression of P62(P<0.05),gradual activation of the AMPK/mTOR pathway with elapse of starvation time,and increase in the intensity of autophagic flux.However,in the HepG2 cells with ATG5 knockdown,starvation treatment led to decreased ATG5 expression,no significant difference in LC3B-II and P62 changes,inhibited autophagic flux,and suppressed cell proliferation(P<0.000 1).Conclusion Human hepatoblastoma HepG2 cells can regulate autophagic flux to against nutritional stress by inducing ATG5 expression.

Objective The study aimed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus pembrolizumab combined with chemotherapy as first-line treatments for advanced lung squa-mous cell carcinoma.Methods We retrospectively reviewed and analyzed the medical records of 116 patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy plus tislelizumab or pembrolizumab in Guangzhou Chest Hospital from September 2020 to April 2024.We focused on analysis of time to treatment failure(TTF)and objective response rate(ORR)as well as disease control rate(DCR)and treatment-related adverse events(TRAEs).Results At a median follow up of 19.7 monyhs,the median TTF was 9.7 months in the tislelizumab group and 7.7 months in the pembrolizumab group(P<0.05).In addition,the ORR in the tislelizumab group was significantly higher than that in the pembrolizumab group(77.6%vs.60.3%,P<0.05),with DCRs of 93.1%and 87.9%,respectively(P=0.342).Regarding safety,the proportions of grade 3 or higher TRAEs and any-grade TRAEs were comparable between the two groups:29.3%and 81.0%in the tislelizumab group,and 32.8%and 87.9%in the pembrolizumab group,respectively.The most common TRAEs in both groups were hematological toxicities.Conclusions Tislelizumab plus chemotherapy demonstrated better efficacy and safety compared to pembrolizumab with chemotherapy as first-line treatment for Chinese patients with advanced lung squamous cell carcinoma.

Objective:To understand the current status of scientific and technological personnel cognition regarding patent transformation and utilization in hospitals, explore the implementation effectiveness and existing problems of hospital patent operation management measures, and thereby identify key areas and provide targeted guidance for subsequent improvement efforts.Methods:A questionnaire survey was conducted among scientific and technological personnel at a tertiary public hospital in Shanghai. The survey assessed their patent knowledge, investigated their training needs related to patent transformation and utilization, and evaluated the perceived importance and satisfaction with the hospital′s patent operation management measures. Descriptive statistics, ANOVA, t-tests, and Importance-Performance Analysis (IPA) were used to analyze the personnel's improvement demands regarding patent operation.Results:A total of 261 scientific and technological personnel were included. Their overall patent knowledge assessment score was relatively low (46.86±15.52), and their training topic needs were dispersed. The mean scores for both importance (4.13±0.74) and satisfaction (3.90±0.80) regarding the 11 hospital patent operation management measures were above the midpoint. IPA results indicated that: four measures, including ″improving patent transformation/utilization regulations″ and ″implementing salary rewards for achievements transformation, ″ should be maintained (high importance, high satisfaction); two measures, including ″establishing special funds for achievements transformation″ and ″introducing professional service agencies″, require concentrated improvement (high importance, low satisfaction); three measures, including ″building medical-industry-academia-research collaboration platforms″ and ″implementing tiered and classified training″, could be opportunistically optimized (low importance, high satisfaction); two measures, including ″integrating achievements transformation into hospital priorities″ and ″linking patent transformation to performance evaluation and professional promotion″, showed no priority for improvement (low importance, low satisfaction).Conclusions:Effective hospital patent operation management necessitates establishing a robust organizational and institutional framework, cultivating scientific talent with a transformation-oriented mindset, optimizing resource inputs such as funding, technology, information, and services, and actively exploring new paradigms for medical-industry-academia-research collaboration.

Objective To investigate the value of procalcitonin-to-albumin ratio(PAR)for predicting 28-day mortality risk in elderly patients with sepsis for optimizing the diagnosis and treatment strategies.Methods The clinical data of 112 elderly patients diagnosed with sepsis in the intensive care unit were retrospectively reviewed and analyzed.Patients were assigned to survivors group or deaths group based on 28-day outcomes.Clinical characteristics and the results of laboratory tests were collected,including procalcitonin(PCT),albumin,and C-reactive protein(CRP).The normally distributed data were compared between groups using t-test.Mann-Whitney U test was adopted for comparing non-normally distributed data.Cox proportional hazards regression model was used to analyze the effects of multiple variables on survival time.Receiver operating characteristic(ROC)curve analysis was performed to determine the sensitivity and specificity of various variables in predicting mortality risk.Results Mechanical ventilation,APACHE Ⅱ scores,and length of hospital stay(all P＜0.05)were significantly different between survivors group and deaths group.Blood culture results showed that Gram-negative bacteria were predominant pathogen(75.9％),especially Escherichia coli(45.5％).Albumin level was significantly lower(P=0.026),while PCT,CRP,and PAR levels were significantly higher(P＜0.05)in the deaths group compared to those in the survivors group.Multivariate Cox regression analysis revealed that PAR was an independent predictor of 28-day mortality(HR=3.72,95％CI:1.98-4.42,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)of PAR was 0.852 in predicting mortality,with a sensitivity of 81.25％and specificity of 87.82％.Conclusions PAR outperformed PCT or albumin alone in predicting 28-day mortality risk in elderly patient with sepsis.For every 0.1 increase in PAR,the risk of mortality increased by 272％.Early monitoring of PAR can assist clinicians in rapidly identifying high-risk patients and optimizing treatment strategies.

Objective To investigate the value of procalcitonin-to-albumin ratio(PAR)for predicting 28-day mortality risk in elderly patients with sepsis for optimizing the diagnosis and treatment strategies.Methods The clinical data of 112 elderly patients diagnosed with sepsis in the intensive care unit were retrospectively reviewed and analyzed.Patients were assigned to survivors group or deaths group based on 28-day outcomes.Clinical characteristics and the results of laboratory tests were collected,including procalcitonin(PCT),albumin,and C-reactive protein(CRP).The normally distributed data were compared between groups using t-test.Mann-Whitney U test was adopted for comparing non-normally distributed data.Cox proportional hazards regression model was used to analyze the effects of multiple variables on survival time.Receiver operating characteristic(ROC)curve analysis was performed to determine the sensitivity and specificity of various variables in predicting mortality risk.Results Mechanical ventilation,APACHE Ⅱ scores,and length of hospital stay(all P＜0.05)were significantly different between survivors group and deaths group.Blood culture results showed that Gram-negative bacteria were predominant pathogen(75.9％),especially Escherichia coli(45.5％).Albumin level was significantly lower(P=0.026),while PCT,CRP,and PAR levels were significantly higher(P＜0.05)in the deaths group compared to those in the survivors group.Multivariate Cox regression analysis revealed that PAR was an independent predictor of 28-day mortality(HR=3.72,95％CI:1.98-4.42,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)of PAR was 0.852 in predicting mortality,with a sensitivity of 81.25％and specificity of 87.82％.Conclusions PAR outperformed PCT or albumin alone in predicting 28-day mortality risk in elderly patient with sepsis.For every 0.1 increase in PAR,the risk of mortality increased by 272％.Early monitoring of PAR can assist clinicians in rapidly identifying high-risk patients and optimizing treatment strategies.

Objective The study aimed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus pembrolizumab combined with chemotherapy as first-line treatments for advanced lung squa-mous cell carcinoma.Methods We retrospectively reviewed and analyzed the medical records of 116 patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy plus tislelizumab or pembrolizumab in Guangzhou Chest Hospital from September 2020 to April 2024.We focused on analysis of time to treatment failure(TTF)and objective response rate(ORR)as well as disease control rate(DCR)and treatment-related adverse events(TRAEs).Results At a median follow up of 19.7 monyhs,the median TTF was 9.7 months in the tislelizumab group and 7.7 months in the pembrolizumab group(P<0.05).In addition,the ORR in the tislelizumab group was significantly higher than that in the pembrolizumab group(77.6%vs.60.3%,P<0.05),with DCRs of 93.1%and 87.9%,respectively(P=0.342).Regarding safety,the proportions of grade 3 or higher TRAEs and any-grade TRAEs were comparable between the two groups:29.3%and 81.0%in the tislelizumab group,and 32.8%and 87.9%in the pembrolizumab group,respectively.The most common TRAEs in both groups were hematological toxicities.Conclusions Tislelizumab plus chemotherapy demonstrated better efficacy and safety compared to pembrolizumab with chemotherapy as first-line treatment for Chinese patients with advanced lung squamous cell carcinoma.

Objective:To understand the current status of scientific and technological personnel cognition regarding patent transformation and utilization in hospitals, explore the implementation effectiveness and existing problems of hospital patent operation management measures, and thereby identify key areas and provide targeted guidance for subsequent improvement efforts.Methods:A questionnaire survey was conducted among scientific and technological personnel at a tertiary public hospital in Shanghai. The survey assessed their patent knowledge, investigated their training needs related to patent transformation and utilization, and evaluated the perceived importance and satisfaction with the hospital′s patent operation management measures. Descriptive statistics, ANOVA, t-tests, and Importance-Performance Analysis (IPA) were used to analyze the personnel's improvement demands regarding patent operation.Results:A total of 261 scientific and technological personnel were included. Their overall patent knowledge assessment score was relatively low (46.86±15.52), and their training topic needs were dispersed. The mean scores for both importance (4.13±0.74) and satisfaction (3.90±0.80) regarding the 11 hospital patent operation management measures were above the midpoint. IPA results indicated that: four measures, including ″improving patent transformation/utilization regulations″ and ″implementing salary rewards for achievements transformation, ″ should be maintained (high importance, high satisfaction); two measures, including ″establishing special funds for achievements transformation″ and ″introducing professional service agencies″, require concentrated improvement (high importance, low satisfaction); three measures, including ″building medical-industry-academia-research collaboration platforms″ and ″implementing tiered and classified training″, could be opportunistically optimized (low importance, high satisfaction); two measures, including ″integrating achievements transformation into hospital priorities″ and ″linking patent transformation to performance evaluation and professional promotion″, showed no priority for improvement (low importance, low satisfaction).Conclusions:Effective hospital patent operation management necessitates establishing a robust organizational and institutional framework, cultivating scientific talent with a transformation-oriented mindset, optimizing resource inputs such as funding, technology, information, and services, and actively exploring new paradigms for medical-industry-academia-research collaboration.

Objective:To explore the characteristics and therapeutic strategies of Pott's puffy tumor（PPT）. Methods:The clinical data of two patients with PPT were retrospectively analyzed and combined with the literature, focusing on the comprehensive analysis of perioperative diagnosis and treatment strategies. Both patients underwent muti-disciplinary treatment, including timely administration of sufficient antibiotics capable of penetrating the blood-brain barrier. Early removal of PPT lesions was performed using a combined internal and external approach under nasal endoscopic guidance. Results:After standardized perioperative management, the symptoms of the two patients were completely relieved, with no recurrence after one=year follow=up. Postoperative complications such as frontal pain, numbness, local depression, or scar hyperplasiawere not present. Conclusion:PPT, being relatively rare and severe, requires careful attention. Key strategies for standardized perioperative management include multi-disciplinary consultation, timely and adequate antibiotic administration, and surgical intervention using a combined intranasal and extranasal endoscopic approach for lesion removal.
Humans ; Pott Puffy Tumor/complications* ; Retrospective Studies ; Tomography, X-Ray Computed ; Endoscopy/adverse effects* ; Postoperative Complications ; Anti-Bacterial Agents/therapeutic use* ; Frontal Sinusitis/complications*

Objective To investigate the longitudinal changes in left ventricular(LV)structure and function after bariatric surgery in obese individuals and their relationship with preoperative left ventricular ejection fraction(LVEF)by cardiac magnetic resonance(CMR)imaging.Methods We prospectively enrolled 75 obese subjects scheduled for laparoscopic sleeve gastrectomy and 46 age and sex-matched healthy controls(the control group).All subjects underwent CMR examination to obtain LV structural parameters,LVEF,and strain parameters.According to their preoperative LVEF,the obese subjects were divided into two obesity groups,including the group of patients with LVEF≥60％(n=43)and the group of patients with 50％≤LVEF＜60％(n=32).LV structural and functional differences between the control group and the two obesity groups were compared.Eventually,38 obese subjects completed the CMR follow-up at 1 month and 12 months after bariatric surgery.The longitudinal changes in LV structure and function after surgery in the LVEF ≥ 60％(n=20)group and the 50％≤LVEF＜60％group(n=18)were compared.Results Before bariatric surgery,the global longitudinal strain was significantly lower in the LVEF ≥ 60％group than that in the control group([-18.36±1.86]％vs.[-19.50±1.53]％,P＜0.05).The global radial([27.70±3.52]％vs.[34.44±4.11]％,P＜0.05),circumferential([-17.35±1.46]％vs.[-19.85±1.42]％,P＜0.05),and longitudinal([-16.22±1.81]％vs.[-19.50±1.53]％,P＜0.05)strain in the 50％≤ LVEF＜60％group was significantly lower than that in the control group.At 12 months after bariatric surgery,the global radial([32.52±7.84]％vs.[30.92±4.27]％,P＞0.05),circumferential([-19.02±2.42]％vs.[-18.63±1.49]％,P＞0.05),and longitudinal([-18.18±2.06]％vs.[-17.78±1.66]％,P＞0.05)strain in the LVEF≥60％group showed no significant difference compared with the baseline findings.In the 50％≤ LVEF＜60％group,the global radial([32.73±5.86]％vs.[26.83±4.85]％,P＜0.05)and circumferential([-19.10±2.00]％vs.[-16.91±2.09]％,P＜0.05)strain was significantly higher than that before surgery.Conclusion LV remodeling is reversed after bariatric surgery in obese subjects,and the longitudinal changes in LV structure and function vary with the preoperative LVEF.