Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

Objective:To develop and validate a perioperative oral care protocol for patients undergoing oral vestibular approach endoscopic thyroid cancer radical surgery, providing practical guidance for clinical nursing.Methods:The protocol was constructed through literature analysis and Delphi expert consultation. A prospective non-randomized controlled study was conducted using convenience sampling, enrolling 60 patients who underwent oral vestibular approach endoscopic thyroid cancer radical surgery at the First Affiliated Hospital with Nanjing Medical University Thyroid Center between August 2023 and May 2024. Participants were divided into control group (from August to December, 2023) and experimental group (from January to May, 2024) based on admission dates with 30 cases in each group. The control group received routine care, while the experimental group received the developed oral care protocolin on the basis of the control group. Postoperative pain scores, mouth-opening difficulties, and oral cleanliness were compared on days 1, 3, and 7 after surgery.Results:The final protocol comprised 7 first-level indicators (team collaboration, health education, preoperative oral assessment, preoperative management, intraoperative management, postoperative management, and discharge follow-up), 17 second-level indicators, and 49 third-level indicators. The control group had 4 males and 26 females, with an age of (29.57 ± 5.34) years; the experimental group had 6 males and 24 females, with an age of (29.87 ± 6.25) years. On postoperative days 1, 3, and 7, the pain scores were 3.87 ± 1.01, 3.30 ± 0.92, and 2.53 ± 0.68 in the control group and 3.20 ± 0.87, 2.10 ± 0.76, and 1.50 ± 0.51 in the experimental group, respectively. The differences between the two groups were statistically significant ( t = 2.89, 5.12, 6.34, all P<0.05). For mouth-opening difficulties, the control group had 6, 13, and 15 patients with grade I on postoperativedays 1, 3, and 7, respectively, while the experimental group had 10, 20, and 25 patients with gradeⅠ. The control group had 20, 14, and 14 patients with gradeⅡonpostoperative days 1, 3, and 7, respectively, while the experimental group had 17, 10, and 5 patients with gradeⅡ. The control group had 4, 3, and 1 patients with grade Ⅲ on postoperative days 1, 3, and 7, respectively, while the experimental group had 3, 0, and 0 patients with grade Ⅲ. There were 0 cases in both groups with grade Ⅳ. The differences between the two groups on postoperative days 3, and 7 were statistically significant ( χ2 = 10.45, 18.67, both P<0.05). For oral cleanliness, the control group had 3, 4, and 5 patients with excellent cleanliness on postoperative days 1, 3, and 7, respectively, while the experimental group had 11, 16, and 19 patients with excellent cleanliness. The control group had 20, 22, and 23 patients with good cleanliness on postoperative days 1, 3, and 7, respectively, while the experimental group had 18, 13, and 10 patients with good cleanliness. The control group had 7 (23.33%), 4 (13.33%), and 2 (6.67%) patients with poor cleanliness on postoperative days 1, 3, and 7, respectively, while the experimental group had 1 (3.33%), 1 (3.33%), and 1 (3.33%) patients with poor cleanliness. The differences between the two groups were statistically significant ( χ2 = 9.19, 11.32, 16.68, all P<0.05). Conclusions:The developed perioperative oral care protocol is scientifically sound, feasible, and practical. Following the intervention, significant decreases in pain scores, alleviation of trismus symptoms, and marked improvements in oral cleanliness were observed in patients compared to pre-intervention assessments, and worth further clinical application.

Objective:To develop and validate a perioperative oral care protocol for patients undergoing oral vestibular approach endoscopic thyroid cancer radical surgery, providing practical guidance for clinical nursing.Methods:The protocol was constructed through literature analysis and Delphi expert consultation. A prospective non-randomized controlled study was conducted using convenience sampling, enrolling 60 patients who underwent oral vestibular approach endoscopic thyroid cancer radical surgery at the First Affiliated Hospital with Nanjing Medical University Thyroid Center between August 2023 and May 2024. Participants were divided into control group (from August to December, 2023) and experimental group (from January to May, 2024) based on admission dates with 30 cases in each group. The control group received routine care, while the experimental group received the developed oral care protocolin on the basis of the control group. Postoperative pain scores, mouth-opening difficulties, and oral cleanliness were compared on days 1, 3, and 7 after surgery.Results:The final protocol comprised 7 first-level indicators (team collaboration, health education, preoperative oral assessment, preoperative management, intraoperative management, postoperative management, and discharge follow-up), 17 second-level indicators, and 49 third-level indicators. The control group had 4 males and 26 females, with an age of (29.57 ± 5.34) years; the experimental group had 6 males and 24 females, with an age of (29.87 ± 6.25) years. On postoperative days 1, 3, and 7, the pain scores were 3.87 ± 1.01, 3.30 ± 0.92, and 2.53 ± 0.68 in the control group and 3.20 ± 0.87, 2.10 ± 0.76, and 1.50 ± 0.51 in the experimental group, respectively. The differences between the two groups were statistically significant ( t = 2.89, 5.12, 6.34, all P<0.05). For mouth-opening difficulties, the control group had 6, 13, and 15 patients with grade I on postoperativedays 1, 3, and 7, respectively, while the experimental group had 10, 20, and 25 patients with gradeⅠ. The control group had 20, 14, and 14 patients with gradeⅡonpostoperative days 1, 3, and 7, respectively, while the experimental group had 17, 10, and 5 patients with gradeⅡ. The control group had 4, 3, and 1 patients with grade Ⅲ on postoperative days 1, 3, and 7, respectively, while the experimental group had 3, 0, and 0 patients with grade Ⅲ. There were 0 cases in both groups with grade Ⅳ. The differences between the two groups on postoperative days 3, and 7 were statistically significant ( χ2 = 10.45, 18.67, both P<0.05). For oral cleanliness, the control group had 3, 4, and 5 patients with excellent cleanliness on postoperative days 1, 3, and 7, respectively, while the experimental group had 11, 16, and 19 patients with excellent cleanliness. The control group had 20, 22, and 23 patients with good cleanliness on postoperative days 1, 3, and 7, respectively, while the experimental group had 18, 13, and 10 patients with good cleanliness. The control group had 7 (23.33%), 4 (13.33%), and 2 (6.67%) patients with poor cleanliness on postoperative days 1, 3, and 7, respectively, while the experimental group had 1 (3.33%), 1 (3.33%), and 1 (3.33%) patients with poor cleanliness. The differences between the two groups were statistically significant ( χ2 = 9.19, 11.32, 16.68, all P<0.05). Conclusions:The developed perioperative oral care protocol is scientifically sound, feasible, and practical. Following the intervention, significant decreases in pain scores, alleviation of trismus symptoms, and marked improvements in oral cleanliness were observed in patients compared to pre-intervention assessments, and worth further clinical application.

Objective To compare the effects of different crown materials on the stress distribution of dental implants by finite ele-ment method.Methods A three-dimensional finite element model of implant-supported crown restoration of the right mandibular first molar was established.Four kinds of crown restoration materials were used,including polymer infiltrated ceramic network Vita Enamic,resin nanoceramic Lava Ultimate,zirconia ceramic Cercon,and polyether-ether-ketone breCAM.A displacement load of 0.01 mm or 200 N was applied to the occlusal surface of the right mandibular first molar,and the analysis of reaction force,the maximum variability of shape,the maximum principal stress,the maximum equivalent stress was performed.Results The results of stress analysis under 0.01 mm displacement load showed that the maximum equivalent stress of Cercon was 937.30 MPa,and that of breCAM was 67.09 MPa.The stress concentration of crowns and implants was obvious.The maximum equivalent stress of the surrounding alveolar bone of Cercon was the highest(26.61 MPa),and that of breCAM was the lowest(3.87 MPa),which was about 1/7 of that of maximum group.The stress concentration range of resin-matrix ceramics and polyether-ether-ketone was relatively small,and the distribution was more uniform.When 200 N was applied,the maximum principal stress and the maximum equivalent stress distribution of the four models were similar,and the maximum variability of shape of breCAM was larger at the loading site.Conclusion Under the same displace-ment load,the stress concentration of polyether-ether-ketone and resin-matrix ceramics crown was lower than that of zirconia.There was no significant difference in stress concentration in the implant and surrounding alveolar bone among polyetheretherketone,resin-ceramic composite,and zirconia crown restorations under the same load.Further research on long-term durability of PEEK and resin-matrix ce-ramicsis needed through practical and clinical trials.

In order to investigate how macrophages promote lipid droplet hoarding in hepatocellular carcinoma cells and to delve into the roles of key metabolic enzymes of lipid droplets in the malignant biology of hepatocellular carcinoma cells, the present study was conducted to induce the generation of Hepa1-6 lipid droplets (LDs) using supernatants from tumor-associated macrophages (TAMs), and found that interleukin-10 (IL-10) in TAMs was found to promote the accumulation of lipid droplets. Acetyl-CoA carboxylase alpha (ACC1) is one of the key enzymes for fatty acid synthesis and influences the development of hepatocellular carcinoma. In this study, ACC1 was found to be highly expressed in LDhigh Hepa1-6, and subsequent blockade of ACC1 activity by means of a small molecule inhibitor of ACC1, siRNA interference, and CRISPR-cas9 knockdown was found to reduce the accumulation of Hepa1-6 lipid droplets, as well as to reduce the malignant biological behavior of Hepa1-6 proliferation, and to promote the occurrence of apoptotic events. In summary, IL-10 released by TAMs promoted lipid droplet formation in hepatocellular carcinoma cells, leading to malignant proliferation and apoptosis of hepatocellular carcinoma cells. ACC1 plays a key role in the promotion of lipid droplet accumulation in hepatocellular carcinoma cells by TAMs and may be regulated by IL-10 released by TAMs, and these findings may provide a new target for hepatocellular carcinoma treatment.

Objective From the perspective of China's health system,evaluate the cost-effectiveness of furmonertinib compared to gefitinib in first-line monotherapy for EGFR mutation-positive advanced non-small cell lung cancer.Methods Based on the FURLONG study of phase Ⅲ clinical trials,a three-state partitioned survival model was constructed and combined with parameters such as treatment cost,utility value,the incidence of adverse reactions,and discount rate;the total incremental cost-effectiveness ratio(ICER)was simulated.Then,the ICER value was compared with the willingness to pay(WTP)value to determine the economic feasibility of furmonertinib compared to gefitinib as a first-line treatment for EGFR mutation-positive advanced non-small cell lung cancer.Results The basic analysis results show that the treatment group with furmonertinib incurred an additional cost of 85 786 yuan compared to the treatment group with gefitinib,but obtained an additional 0.62 QALYs,with an incremental cost-effectiveness ratio of 138 306 yuan,which is less than three times China's per capita GDP.One-way sensitivity analysis shows that the best support treatment cost,PFS utility value,and PD utility value significantly impact the ICER results.The results of probability sensitivity analysis show that when the WTP is three times China's per capita GDP,the probability of economic viability of the furmonertinib group compared to the gefitinib group is 100.0%.The scenario analysis results verified the robustness of the underlying analysis results.Conclusion Under the willingness to pay threshold of three times China's per capita GDP in 2022,Choosing furmonertinib as a first-line monotherapy for EGFR mutation-positive advanced non-small cell lung cancer is more cost-effective than gefitinib.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective:To investigate the agreement of ultrasound derived fat fraction (UDFF) with magnetic resonance imaging proton density fat fraction (MRI PDFF) on evaluating hepatic steatosis, and the performance of UDFF on diagnosing metabolic dysfunction associated steatotic liver disease (MASLD).Methods:One hundred and twenty-five volunteers and one hundred and seven inpatients who underwent abdominal ultrasound examination in Zhongda Hospital Southeast University from November 2023 to February 2024 were prospectively enrolled.UDFF and MRI PDFF were applied to evaluate hepatic steatosis. Spearman correlation test and Bland-Altman plot were applied to analyze the agreement of UDFF and MRI PDFF. Receiver operating characteristic curve (ROC) was applied to calculate the performance of UDFF on diagnosing MASLD.Results:In our participants, compared to individuals without hepatic steatosis, patients with MASLD had higher body mass index (BMI), waist-to-hip ratio, prevalence of diabetes mellitus, levels of alanine transaminase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), triglyceride, and UDFF (all P<0.05). The percentage of hepatic steatosis measured by UDFF and MRI PDFF was strongly correlated[ρ=0.873(95% CI=0.837-0.901), P<0.001]. UDFF performed excellent for diagnosing MASLD with an area under the curve (AUC) of 0.983(95% CI=0.956-0.995, P<0.001), and was better than semi-quantitative assessment based on two-dimensional ultrasound as well as ultrasound attenuation parameter. The optimal cut off value of UDFF to diagnose MASLD was ≥6%. Conclusions:The percentage of hepatic steatosis measured by UDFF and MRI PDFF agrees with each other, and UDFF obtains an excellent performance on diagnosing MASLD, so that UDFF should be considered a reliable imaging technique for quantitively evaluating hepatic steatosis and diagnosing MASLD.