OBJECTIVE To evaluate the cost-effectiveness of iruplinalkib for ALK-positive non-small cell lung cancer （NSCLC） patients who had not previously received ALK-tyrosine kinase inhibitors （TKIs） from the perspective of the Chinese healthcare system. METHODS Based on the INSPIRE clinical trial， a three-health state partitioned survival model was developed to simulate the progression of disease， with model cycle of 3 weeks and a life-year time range of 15 years； the discount rate was 5%. For the treatment of ALK-positive advanced NSCLC， total cost， quality-adjusted life year （QALY）， and incremental cost- effectiveness ratio （ICER） were compared between iruplinalkib and crizotinib； using 1-3 times China’s per capita gross domestic product （GDP） （89 358-268 074 yuan） in 2023 as the willingness-to-pay （WTP） threshold， the cost-effectiveness of two regimens were compared. The sensitivity analysis and scenario analysis （altering the distribution of survival curves， utility values） were conducted to assess model robustness. RESULTS Compared with the crizotinib regimen， the ICER for the iruplinalkib regimen was 194 412.74 yuan/QALY， which was below the WTP threshold of three times China’s per capita GDP in 2023 yuan）. The results under the scenario of altering the survival curve distribution were consistent with the base case analysis. However， after increasing the utility value of the disease progression state， the ICER exceeded the WTP threshold， and iruplinalkib no longer had a cost-effective advantage. The results of the one-way sensitivity analysis indicated that the cost of iruplinalkib and the utility values of disease progression states had a significant impact on the ICER. The probabilistic sensitivity analysis confirmed the robustness of the base case analysis results. CONCLUSIONS From the perspective of China’s healthcare system， compared with crizotinib regimen， the therapy with iruplinalkib is cost-effective for ALK-positive NSCLC patients who have not previously received ALK-TKIs.

Objective:To discuss the effect of royal jelly acid(10-HDA)on the proliferation and migration of the human colon cancer SW620 cells based on the network pharmacology,and to clarify its related molecular mechanism.Methods:The active ingredients such as 10-HDA and their corresponding targets were retrieved by using the keyword"royal jelly"from the Traditiomal Chinese Medicine Systems Pharmacology(TMSCP)Database and the Traditiomal Chinese Medicine Integrated Database(TCMID);the small molecule targets were predicted by the Swiss Target Prediction Database.The GeneCards Database and the Online Mendelian Inheritance in Man(OMIM)Database were used to obtain the targets with the keyword"Colon Cancer";the protein-protein interaction(PPI)network was constructed by using the String Database and Cytoscape 3.8.0 Software to screen the core targets;the Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were analyzed by Metascape Database;the specific ingredient 10-HDA was screened for the in vitro activity experiments.The human colon cancer SW620 cells with good growth status were divided into control group and different doses(1,5,10,15,and 20 mmol·L-1)of 10-HDA groups.The viabilities of the cells in various groups were detected by MTT method and the survival rates of the cells were calculated.The SW620 cells were divided into control group,low dose(5 mmol·L-1)of 10-HDA group,middle dose(10 mmol·L-1)of 10-HDA group,and high dose(15 mmol·L-1)of 10-HDA group;Hoechst33342 staining method was used to observe the morphology of the cells in various groups;cell scratch test was used to detect the scratch healing rates of the cells in various groups;flow cytometry was used to detect the percentages of the cells at different cell cycles in various groups;biochemical method was used to detect the activities of total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)in the cells in various groups;Western blotting method was used to detect the expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),cysteine-containing aspartate proteolytic enzyme-9(Caspase-9),glycogen synthase kinase 3β(GSK3β),β-catenin,and cyclin D1 proteins in the cells in various groups.Results:Six active ingredients of royal jelly were screened out by the TCMSP Database,and 28 core targets of 10-HDA in the treatment of colon cancer were obtained.The GO function enrichment analysis mainly included the signaling pathways such as cell proliferation and apoptosis.The KEGG signaling pathway enrichment analysis included the cell cycle,prostate cancer,cell senescence,and p53 signaling pathways;the GSK3β/β-catenin signaling pathway was closely related to the cell cycle.Compared with control group,the viabilities of the cells in 5,10,15,and 20 mmol·L-110-HDA groups were decreased in a dose-dependent manner(P<0.05 or P<0.01),the numbers of apoptotic cells in different doses of 10-HDA groups were significantly increased,and the scratch healing rates of the cells were significantly decreased(P<0.05 or P<0.01);the percentages of the cells at S phase in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),the activities of T-AOC and SOD in the cells in different doses of 10-HDA groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression level of Bcl-2 protein in the cells in low dose of 10-HDA group was significantly decreased(P<0.01),and the expression level of GSK3β protein was significantly increased(P<0.05);compared with control group,the expression levels of Bax,Caspase-3,Caspase-9,and GSK3β proteins in the cells in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),and the expression levels of Bcl-2,β-catenin,and CyclinD1 proteins were significantly decreased(P<0.01).Conclusion:10-HDA can significantly inhibit the proliferation and migration of the colon cancer cells and promote the apoptosis and oxidation levels of the colon cancer cells,and its mechanism may be related to the activation of the GSK3β/β-catenin signaling pathway.

Objective To compare the efficacy of retroperitoneal robot-assisted laparoscopic partial nephrectomy(RALPN)in the treatment of ventral and dorsal renal tumor.Methods The clinical data of 131 patients with renal tumor who underwent retroperitoneal RALPN at our hospital during Jan.2021 and Feb.2024 were retrospectively analyzed.The patients were divided into the ventral renal tumor group(n=35)and dorsal renal tumor group(n=96)according to preoperative images.Perioperative outcomes and prognosis were compared between the two groups.Results All 131 surgeries were successfully completed without conversion to open surgery or abdominal organ injury.There were no significant differences in warm ischemia time[median(interquartile range,IQR):20(16.75)min vs.22(IQR:15.25)min],operation time[57.0(IQR:29.5)min vs.58.5(IQR:39.75)min],estimated intraoperative blood loss[50(IQR:80)mL vs.50(IQR:80)mL],proportion of patients with intraoperative blood transfusion(0 vs.2.1％),proportion of patients using four arms during operation(42.9％vs.37.5％),postoperative reduction of hemoglobin(Hb)[(-12.9±9.0)g/L vs.(-11.5±9.4)g/L],reduction of estimated glomerular filtration rate(eGFR)[(-3.8±12.4)mL/min vs.(-7.0±13.6)mL/min],postoperative hospital stay[4(IQR:0)d vs.4(IQR:2)d],and proportion of meeting"Trifecta"criteria(94.3％vs.86.5％,P＞0.05).During the median follow-up of 9.8(5.5,24.0)months,no death occurred,and no recurrence or metastasis were observed except that bone metastasis occurred in 1 patient in the dorsal renal tumor group.Conclusion Both ventral and dorsal renal tumors can be treated with retroperitoneal RALPN,and the surgical outcomes of both are comparable.

Objective To investigate the mechanism of circadian clock protein Bmal1(Bmal1)on renal injury with chronic periodontitis,we established an experimental rat periodontitis model.Methods Twelve male Wistar rats were randomly divided into control and periodontitis groups(n=6,each group).The first maxillary molars on both sides of the upper jaw of rats with periodontitis were ligated by using orthodontic ligature wires,whereas the control group re-ceived no intervention measures.After 8 weeks,clinical periodontal parameters,including probing depth,bleeding index,and tooth mobility,were evaluated in both groups.Micro-CT scanning and three-dimensional image recon-struction were performed on the maxillary bones of the rats for the assessment of alveolar bone resorption.Histopatholo-gical observations of periodontal and renal tissues were conducted using hematoxylin-eosin(HE)and periodic acid-Schiff(PAS)staining.Renal function indicators,such as creatinine,albumin,and blood urea nitrogen levels,and oxida-tive stress markers,including superoxide dismutase,glutathione,and malondialdehyde levels,were measured using bio-chemical assay kits.MitoSOX red staining was used to detect reactive oxygen species(ROS)content in the kidneys.The gene and protein expression levels of Bmal1,nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in rat renal tissues were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)and immuno-histochemical staining.Results Micro-CT and HE staining results showed significant bone resorption and attachment loss in the maxillary first molar region of the periodontitis group.Histological examination through HE and PAS staining revealed substantial histopathological damage to the renal tissues of the rats in the periodontitis group.The findings of the assessment of renal function and oxidative stress markers indicated that the periodontitis group exhibited abnormal levels of oxidative stress,whereas the renal function levels showed abnormalities without statistical significance.Mito-SOX Red staining results showed that the content of ROS in the renal tissue of the periodontitis group was significantly higher than that of the control group,and RT-qPCR and immunohistochemistry results showed that the expression levels of Bmal1,Nrf2,and HO-1 in the renal tissues of the rats in the periodontitis group showed a decreasing trend.Conclu-sion Circadian clock protein Bmal1 plays an important role in the oxidative damage process involved in the renal of rats with periodontitis.

Objective This study aims to explore changes in uncoupling protein 2(UCP2)in experimental periodonti-tis-associated renal injury induced by ligation and investigate the effect of UCP2 on renal injury induced by periodontitis.Methods Twelve Wistar male rats were randomly divided into two groups:control and periodontitis groups.A periodon-tal model was built by ligating the maxillary first molars area with 0.2 mm orthodontic ligature wire.After 8 weeks,the in-traoral condition of the rats was observed and periodontal clinical indices such as gingival bleeding index(BI),periodontal probing depth(PD),and tooth mobility(TM)were detected.The maxillary bone was scanned by Micro CT to observe the alveolar bone resorption.The tissue mineral density(TMD),bone mineral density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular bone separation(Tb.Sp)were recorded,and the distance from the enamel bone boundary to the alveolar crest(CEJ-ABC)of the maxillary first molar was measured.The oxidative stress indexes such as malondialdehyde,glutathione(GSH),and superoxide dismutase(SOD)were detected using frozen rat kidney tissue.The gene expression of UCP2,nuclear factor erythroid 2-related factor 2(Nrf2),and peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)was observed by quantitative real-time polymerase chain reaction(qRT-PCR)test.The gingival tissue of the rats was used for immunohistochemical staining to observe the expression of the UCP2 protein.The fixed rat kidney tissue was used for hematoxylin-eosin(HE),periodic acid-schiff(PAS),MitoSOX Red,JC-1,and immu-nohistochemical staining to observe the renal histopathology,the level of reactive oxygen species(ROS),the level of mito-chondrial membrane potential,and the expression of UCP2,Nrf2,and PGC-1α protein.Rat serum was collected to detect renal function indices,namely,blood urea nitrogen(BUN),creatinine(Cre),and albumin(Alb).Results Compared with the control group,the periodontitis group showed red,swollen,and soft gingival tissue,with gingival probing bleeding,periodontal PD increased,tooth loosening,alveolar bone resorption,decreased TMD,BMD,BV/TV,and Tb.Th indices,and increased Tb.Sp index,CEJ-ABC,and gingival UCP2 protein expression.Compared with the control group,the levels of MDA and ROS in the kidney tissue of periodontitis rats and the gene and protein expression of UCP2 increased,and the levels of MMP,GSH,and SOD and the gene and protein expression of Nrf2 and PGC-1α decreased.Renal functional indi-ces,namely,BUN,Cre,and Alb,were not significantly different between the two groups.Conclusion UCP2 may play a role in renal injury induced by periodontitis through oxidative stress.

OBJECTIVE To analyze the changes of temporary abnormal intraepithelial papillary capillary loop(IPCL)in the surgical area of early glottic laryngeal cancer after CO2 laser resection.METHODS A retrospective study was conducted on early-stage glottic carcinoma patients who visited the Department of Otolaryngology,Head and Neck Surgery at the Second Affiliated Hospital from January 2017 to November 2023.Patients who underwent CO2 laser surgery accepted electronic laryngoscopy examination at 1 month,3 months,and 6 months postoperatively(including white light endoscopy and narrowband imaging endoscopy(NBI),and their medical history,treatment methods,laryngoscopy images,imaging data,and pathological results before and after treatment were systematically collected.The changes in laryngoscopy characteristics at different follow-up times after surgery were analyzed.RESULTS This study included 55 patients with non recurrent early glottic carcinoma who underwent CO2 laser surgery.At 1 month,3 months,and 6 months after surgery,there were significant differences in the proportion of patients with pseudomembrane coverage(72.73%vs.25.45%vs.7.27%),granulation formation(60.00%vs.34.55%vs.1.82%),and abnormal IPCL(23.64%vs.7.27%vs.0.00%)on the surface of the surgical area(P<0.001),and abnormal IPCL(mainly type Va and Vb)can be observed under NBI endoscopy from 1 month to 3 months after surgery.Within 6 months after surgery,the pseudomembrane detachment,granulation regression,scar formation,and abnormal IPCL in the surgical area disappeared.CONCLUSION Early glottic carcinoma patients may experience temporary abnormal IPCL within 3 months after receiving CO2 laser resection,but the abnormal IPCL could disappear within 6 months after surgery for some patients.Therefore,close observation is necessary within 6 months after surgery and there is no need for urgent biopsy.

This ENETS guidance for well-differentiated nonfunctioning pancreatic neuroendocrine tumours(NF-Pan-NET),which published on Journal of Neuroendocrinology(2023),has been developed by a multidisciplinary working group,and provides up-to-date and practical advice on the management of these tumours.In this guideline,the authors discussed 10 troublesome questions about clinical practice,and summarized the extensive experience of their centers treating patients with NF-Pan-NET,and suggested that multidisciplinary participation is an essential part of NF-Pan-NET diagnosis and treatment.This paper aims to interpret the key contents of the guidelines in order to provide standardized clinical diagnosis and treatment procedures in NF-Pan-NET.

Objective:To discuss the feasibility and safety of robot-assisted laparoscopic retroperitoneal tumor resection in prone position.Methods:From August 2023 to January 2024, a total of eight patients with retroperitoneal tumors from the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed, including two males and six females. The average age was (47.4±12.5) years, average BMI was (24.4±3.5) kg/m 2 and median ASA grade was 2(2, 3). Retroperitoneal tumors were identified preoperatively through CT or MRI. The imaging revealed 4 cases of adrenal tumors located on the left side, 2 on the right side, and 2 non-adrenal tumors situated on the left side. The preoperative diagnoses included 2 cases of non-functional adrenal tumors, 2 cases of pheochromocytoma, 1 case of Cushing’s syndrome, 1 case of metastatic renal cell carcinoma, and 2 cases of non-adrenal tumors. Robot-assisted laparoscopic retroperitoneal tumor resection was performed with all patients in prone position. The inferior margin of the fourth lumbar vertebra (L4) was determined by the line connecting the highest points of the iliac crests bilaterally. Subsequently, the inferior margins of the L1-L3 vertebrae were sequentially identified. The surgical field was then divided into three equal segments, utilizing the posterior midline of the spine and the midaxillary line as boundaries. The medial division was situated approximately at the lateral border of the vertical spinal muscles, while the lateral division was placed near the tip of the 12th rib. A longitudinal incision of approximately 3 cm in length was created within the lateral division between L2 and L3 for the insertion of a camera trocar. The extraperitoneal space was subsequently dilated using a self-made balloon, and two 8 mm trocars were placed as operative ports along the medial division and the midaxillary line, respectively, under finger guidance. Assistance trocars, one or two 12 mm in diameter, were introduced above the level of the iliac crest. During the operation, the extraperitoneal adipose tissue was removed and the Gerota's fascia was opened. For non-adrenal retroperitoneal tumours, the major blood vessels around the tumour were suspended and fixed, by titanium clips or Hem-o-lok clips to dissect the small arteries and veins, and the tumour was carefully isolated and completely resected. For adrenal tumours, the fat capsule around the upper pole of the kidney were removed, the adrenal gland was exposed, and then the tumour was removed completely along its capsule. If total adrenalectomy is performed, the central adrenal vein was clamped and dissected. The periphery of the adrenal gland was gradually dissected until the adrenal gland was completely removed.The perioperative data, including patient positioning time, trocar placement time, operation time, intraoperative blood loss, postoperative complications, postoperative hospital stay, and postoperative drainage tube removal time, as well as recurrence and metastasis, were recorded.Two patients underwent partial nephrectomy due to renal tumor, and only the time for retroperitoneal tumor resection was included in calculating operation time. Results:All 8 surgeries were successfully completed without dramatic blood pressure fluctuations.There was no conversion to open surgery or abdominal organ injury. The patient positioning time was (5.1±0.4) minutes, trocar placement time was (16.6±1.3) minutes, operation time was (28.8±13.8) minutes, intraoperative blood loss was (65.0±28.7) ml, postoperative hospital stay was (3.6±0.9) days, and drainage tube removal time was (2.8±1.0) days. No intraoperative or postoperative blood transfusions were required. Postoperatively diagnosed pathologies included: 2 cases of adrenal pheochromocytoma, 2 cases of adrenal sebaceous adenoma, 2 cases of retroperitoneal schwannoma, 1 case of adrenal myelolipoma, and 1 case of adrenal metastatic renal cell carcinoma. The average tumor size for all patients was (4.3±1.5) cm. After a follow-up of 2.0-7.2 months, there were no recorded postoperative complications, including haemorrhage, infections, acute hypotension, or adrenocortical insufficiency. Additionally, no evidence of tumor recurrence or metastasis was observed up during foolow-up.Conclusions:Robot-assisted laparoscopic retroperitoneal tumor resection in prone position could be a safe and feasible surgical approach with short operative time, low bleeding, and fast postoperative recovery.

As a natural drug delivery carrier with rough and porous surface and hollow core， yeast microcapsules have good safety， high targeting and high stability， and have excellent application prospects in oral drug delivery systems. Yeast cells can be treated and washed with acid-base and organic solvents to obtain loose and porous yeast microcapsules. Yeast microcapsules can encapsulate drugs through electrostatic interactions， passive diffusion， hydrophobic interaction and other methods. The surface of yeast microcapsules is mainly composed of β-glucan， which can maintain stability in the gastrointestinal environment； it can be recognized by the surface-related receptors of immune cells， thus activating the immune response， and can be transported to the lesion site with the movement of lymphocytes after being ingested. Yeast microcapsules are safe and very suitable for delivering vaccines， anti-inflammatory drugs， and anti-tumor drugs. They can not only achieve oral delivery of the aforementioned drugs， but also enhance drug efficacy and improve drug targeting. In the future， more research on systemic transport mechanisms or the development of more efficient combination drug delivery systems can be carried out to fully exhibit the clinical value of yeast microcapsules.

Abstract The physical health of children and adolescents has received widespread attention in recent years, and a series of problems due to unbalanced energy expenditure have come into focus. Energy expenditure in children and adolescents is influenced by multiple factors including body composition and physical activity level. By analyzing and summarizing the characteristics and specificities of energy expenditure in children and adolescents at different ages, the review aims to formulate a targeted design and implementation plans for future intervention studies.