Melanoma is characterized by high malignancy, ranking the third among skin malignancies, and is associated with lack of specific treatment options and poor prognosis. Therefore, the development of effective therapies for melanoma is imperative. A critical challenge in addressing subcutaneous disease lies in overcoming the skin barrier. In this study, we engineered a microneedle (MN) system that integrates chemotherapy, photothermal therapy (PTT), and targeted therapy to enhance anti-tumor efficacy while effectively penetrating the skin barrier. In vitro studies have demonstrated that the MN drug delivery system (DDS) can effectively penetrate the stratum corneum of the skin, deliver therapeutics to subcutaneous tumor sites, and establish a drug reservoir at these locations to exert anti-tumor effects. Cellular experiments indicated that the engineered PTT chemotherapy-targeted MNs can be internalized by tumor cells, exhibiting enhanced cytotoxicity against them. In vivo pharmacological investigations revealed that the combination of PTT and chemotherapy delivered via this MN DDS produced synergistic anti-tumor effects, achieving a tumor inhibition rate of up to 98.15%. This in situ DDS minimizes involvement with other organs, significantly reducing chemotherapy-related side effects. In summary, the PTT chemotherapy-targeted MNs developed in this study demonstrate promising application potential by enhancing anti-tumor efficacy while minimizing adverse effects.

Objective To investigate the predictive value of serum interleukin-17(IL-17)combined with eotaxin-3 for poor prognosis in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods A total of 213 patients with AECOPD admitted to Beijing Municipal Armed Police Force Hospital from May 2018 to July 2023 were selected as the disease group.According to the prognosis of patients,they were divided into good prognosis group(133 cases)and poor prognosis group(80 cases).At the same time,205 physical examination healthy people in Beijing Municipal Armed Police Force Hospital were selected as the healthy group.The serum levels of IL-17 and eotaxin-3 were detected by enzyme-linked immu-nosorbent assay.The clinical data of poor prognosis group and good prognosis group were compared.Pearson correlation analysis was used to analyze the correlation between serum IL-17 level and eotaxin-3 in AECOPD patients.Multivariate Logistic regression analysis was used to analyze the related factors affecting the progno-sis of AECOPD patients.The receiver operating characteristic(ROC)curve was used to evaluate the predic-tive value of serum IL-17 and eotaxin-3 levels for the prognosis of AECOPD patients.Results Compared with the healthy group,the serum levels of IL-17 and eotaxin-3 were increased in the disease group(P<0.05).Compared with the good prognosis group,the poor prognosis group had significant increases in serum IL-17 and eotaxin-3 levels(P<0.05).Serum IL-17 level was positively correlated with eotaxin-3 in AECOPD pa-tients(r=0.537,P<0.001).There were significant differences in Global Initiative for Chronic Obstructive Lung Disease(GOLD)grade,blood oxygen partial pressure(PaO2)and carbon dioxide partial pressure(PaCO2)between the poor prognosis group and the good prognosis group(P<0.05).GOLD grade,PaCO2,serum IL-17 and eotaxin-3 levels were risk factors for poor prognosis in patients with AECOPD(P<0.05),and PaO2 was a protective factor for poor prognosis in patients with AECOPD(P<0.05).The area under the curve of serum IL-17 and eotaxin-3 combined to predict the prognosis of AECOPD patients was 0.885,the sensitivity was 80.00%,and the specificity was 83.46%,which was better than that of IL-17 and eotaxin-3 a-lone(Zcombiation-IL-17=4.045,P<0.001,Zcombiation-eotaxin-3=3.254,P=0.001).Conclusion The serum levels of IL-17 and eotaxin-3 are increased in AECOPD patients.The combination of IL-17 and eotaxin-3 has predictive value for the prognosis of AECOPD patients.

【Objective】 To explore the correlation between body mass index (BMI) and lipid indexes with prostate volume in patients with benign prostatic hyperplasia (BPH) so as to provide reference for the clinical prevention of this disease. 【Methods】 Clinical data of 578 patients admitted to the Department of Urology of Chinese PLA General Hospital during Jan.2014 and Dec.2022 were collected.The patients underwent initial prostate puncture biopsy or prostatectomy and BPH was confirmed pathologically.The patients’ age, time of onset of the disease, BMI, past medical history and biochemical indexes were analyzed.According to the total prostate volume (TPV) grading, the patients were divided into TPV>75 mL and TPV≤75 mL groups.The general data of the two groups were compared, and predictors of TPV were determined with linear regression analysis.The samples were stratified with BMI to observe the differences in the effects of apolipoprotein B (ApoB) on TPV. 【Results】 There were 215 cases in the TPV>75 mL group and 363 cases in the TPV≤75 mL group.The levels of BMI, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) were higher in the TPV>75 mL group (P<0.01).Multivariate linear regression analysis showed that age (β=0.604, P=0.003), BMI (β=2.000, P<0.001), ApoB (β=23.792, P<0.001) and TPV had a significant positive linear correlation; after adjusting for the confounders of age and BMI, ApoB was not linearly correlated with TPV in BPH population with BMI<24 (P>0.05), and ApoB predicted prostate volume growth in overweight and obese BPH population respectively (β=26.411, P=0.011; β=47.602, P=0.017). 【Conclusion】 Age, ApoB and BMI can be used as predictors of volume growth in BPH patients, which can help further research on the pathogenesis and progression of BPH.

Surgical resection in patients with advanced primary carcinoma of liver has high risks of early recurrence and incidence of portal vein tumor thrombus, caused by insufficient resi-dual liver volume after two-steps hepatotomy. At present, the treatment for patients with advanced primary carcinoma of liver is limited, thus can't satisfy the requirement of patient for treatment. The authors introduce the clinical experience of a patient with hepatocellular carcinoma and insufficient residual liver volume who underwent preventive immunotherapy plus target therapy after associa-ting liver partition and portal vein ligation for staged hepatectomy, in order to provide reference for relevant treatment.

Objective:To evaluate the safety and clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with portal vein embolization (PVE) and percutaneous microwave ablation liver partition with PVE for planned hepatectomy in patients with hepatocellular carcinoma (HCC) with insu-fficient remnant liver volume.Methods:The clinical data of 51 patients with initially unresectable HCC due to insufficient remnant liver volume admitted to Zhejiang Provincial Tongde Hospital and Zhejiang Provincial People’s Hospital from January 2014 to December 2021 were retrospectively analyzed, including 37 males and 14 females, aged (56.7±11.2) years old. Patients were divided into two groups according to the treatment prior to hepatectomy: percutaneous microwave ablation liver partition combined with PVE (AP group, n=12) and TACE with PVE (TP group, n=39). Patients who successfully underwent planned hepatectomy in the above two groups were marked as resectable AP group ( n=10) and the resectable TP group ( n=29), respectively. Clinical data including the waiting time for surgery and the incidence of complications were analyzed. Patients were followed up by telephone or outpatient review. Kaplan-Meier and log-rank analysis were used for survival comparison. Results:The FLR growth rate was higher in AP group [76.5% (65.3%, 81.6%)] than that in TP group [31.4% (28.2%, 41.9%), P<0.01]. The waiting time for planned hepatectomy in the resectable AP group was 12.0 (11.3, 14.5) d, shorter than that in the resec-table TP group [21.0 (15.0, 29.0) d, P<0.05]. The incidence of postoperative complications was higher in the resectable AP group than that in the resectable TP group [80.0% (8/10) vs. 27.6% (8/29), P<0.05]. There was one perioperative death in the resectable AP group. The survival rate after PVE was lower in AP group than that in TP group, and the survival rate after hepatectomy was also lower in the resectable AP group than that in the resectable TP group (all P<0.05). Conclusion:For HCC patients with insufficient FLR, TACE combined with PVE is a safe and effective method for enlargement of liver remnant, whereas percutaneous microwave ablation liver partition with PVE showed a poor prognosis, despite the higher rate of FLR enlargement and shortened the waiting time for planned hepatectomy.

Objective:To design a modified S1PR3 specific agonist, GPS-725.017, and investigate its protective effect on acute lung injury by promoting macrophage clearance of bacteria.Methods:A short peptide derived from the intracellular region of S1PR3 receptor was named GPS725.017, which was modified with norleucine (Nle) and myristicacid (myr) at its N terminus. Mice were divided into the sham operation group, solvent group and GPS-725.017 treatment group. The acute lung injury model was induced by endotracheal injection of E. coli (5×10 6 CFU), and the experimental group was treated with GPS-725.017 (10 mg/kg). The 48-h survival rate of mice was recorded. After 5 h of modeling, the bacterial load and inflammatory cytokines in peripheral blood and lung were detected, and Vps34 protein content in alveolar macrophages was determined by Western blot. After 12-h of modeling, lung tissues were collected for H&E staining and pathological scores. Results:Compared with the solvent group, the survival rate of mice in the GPS-725.017 treatment group was significantly improved ( P<0.01), the bacterial CFU in blood and alveolar lavage fluid was significantly lower than that in the solvent group ( P<0.001), and the levels of TNF-α and IL-1β in blood and alveolar lavage fluid were significantly lower than those in the solvent group ( P<0.001). Western blot showed that the expression level of Vps34 protein in alveolar macrophages was significantly higher than that in the solvent group ( P<0.01). Histopathology result showed that the pathological damage of lung in the treatment group was significantly less than that in the solvent group ( P<0.001). Conclusions:The modified synthetic S1PR3 specific agonist GPS-725.017 could specifically activate the S1PR3 receptor on the membrane of alveolar macrophages and up-regulate the expression level of intracellular Vps34 protein, which can promote the removal of bacteria in alveolar macrophages, significantly reduce the degree of lung injury and improve the survival rate in ALI mice.

Objective: To analyze the alterations and clinical significance of serum calcium binding protein S100A8/A9 and soluble receptor for advanced glycation end products (sRAGE) levels in patients with chronic obstructive pulmonary disease(COPD). Methods: Enzyme-linked immonosorbent assay was established to detect serum levels of S100A8/A9 and sRAGE in 203 patients with COPD[male166, female 37, aged 52-92 years, average years(69.72±9.079)] and in 41 smoking elderly non-COPD patients[male 35,female 6, aged 55-89 years, average years(68.66±8.74)], and 167 non-smoking healthy subjects as the control group[male 132, female 35, aged 57-92 years, average years(69.13±7.21)] from April 2018 to January 2019. The relationship between the S100A8/A9, sRAGE and clinical biomarkers [the percentage of fored expiratory volume in one second(FEV₁) in the predicted value, FEV₁/fored vital capacity(FVC), neutrophile granulocyte(NEU)%, pack-year] were investigated. The diagnostic value of S100A8/A9, sRAGE and their combined detection for COPD was analyzed using the subject operating characteristic curve. Results: The serum S100A8/A9 level [(2.70±1.11)μg/ml] in COPD patients was significantly higher than that in the smoking control group [(1.65±0.63) μg/ml] and the non-smoking control group[(0.99±0.48)μg/ml], t=5.807, P<0.000 1; t=18.45, P<0.000 1. The serum S100A8/A9 levels in patients with COPD[GOLD Ⅰ(2.08±1.08) μg/ml, GOLDⅡ (2.58±1.06) μg/ml, GOLD Ⅲ (2.69±1.12) μg/ml, GOLDⅣ (2.95±1.10)μg/ml] were significantly higher than the non-smoking control group(0.99±0.48)μg/ml, t=6.616, P<0.000 1; t=14.56, P<0.000 1; t=17.10, P<0.000 1; t=18.09, P<0.000 1.The serum sRAGE level [(0.29±0.25)ng/ml] in COPD patients was significantly higher than that in the smoking control group[(0.60±0.24)ng/ml] and the non-smoking control group[(0.85±0.35)ng/ml], t=7.367, P<0.000 1; t=18.14, P<0.000 1. The serum sRAGE levels in patients with COPD[GOLD Ⅰ(0.46±0.40),GOLDⅡ (0.28±0.25),GOLD Ⅲ (0.29±0.25),GOLD Ⅳ (0.25±0.19)ng/ml] were significantly lower compared with non-smoking control group[(0.85±0.35)ng/ml], t=3.459, P=0.000 5; t=10.23, P<0.000 1; t=13.95, P<0.000 1; t=11.70, P<0.000 1. Serum S100A8/A9 levels were positively correlated with smoking amount and NEU% (r=0.458 5, P<0.000 1; r=0.228 3, P=0.001 1), negatively correlated with FEV₁/FVC, the percentage of FEV₁ in the predicted value, and sRAGE(r=-0.190 6, P=0.006 4; r=-0.186 3, P=0.007 8; r=-0.201 7, P=0.003 9). sRAGE levels were negatively correlated with NEU% (r=-0.155 9, P=0.026 4). In the ROC curve, the area under the curve of S100A8/A9, sRAGE and combined detection were 0.922[95%CI(0.897-0.947)], 0.926[95%CI(0.899-0.952)]and 0.966 [95%CI(0.950-0.983)], respectively. Conclusion S100A8/A9 and sRAGE are closely correlated with the degree of airflow constrains and the levels of serum inflammatory mediators, which are expected to be as potential biomarkers of COPD.

Objective To explore the value of transcatheter arterial chemoembolization (TACE) combined with portal vein embolization (PVE) prior to laparoscopic right hemihepatectomy (LRH) in the treatment of large liver tumor.Methods A retrospective study was conducted based on the clinical data of 8 patients with large liver tumor undergoing PVE combined with TACE before scheduled LRH,with 4 cases receiving simultaneous TACE + PVE and the other 4 cases doing sequential TACE + PVE.Results The interval between TACE and PVE was 14-29 d in sequential group,and the interval between PVE and surgery was 13-30 d.Patients in simultaneous treatment group encountered more prominent elevation of transaminase after PVE and TACE,but they recovered to comparable levels with the sequential group before surgery.The average standard future liver remnant (sFLR) increased from 35.3％ ± 4.9％ to 48.7％ ± 5.1％ before surgery.LRH was performed sucessfully in all patients with no conversion and perioperative death.Complications occurred in 2 cases,including pulmonary infection and bile leakage.The median hospital stay was 36 days.All patients were survival in the 25 months median follow up time including 2 recurrence cases.Conclusions TACE combined with PVE prior to LRH in the treatment of large liver tumor is safe and feasible.

Objective To study the safety and feasibility of laparoscopy combined with holmium laser in the treatment of chronic pancreatitis complicated with pancreatic ductal stones.Methods To compare the clinical data in patients who underwent laparoscopy combined with holmium laser (10 patients,group A) with those who underwent laparoscopy only (21 patients,group B) at Zhejiang Provincial People' s Hospital from January 2012 to August 2018.The operation time,intraoperative blood loss,intraoperative conversion rate,pancreatic ductal incision length,postoperative pancreatic fistula rate,length of postoperative hospital stay,residual stone rate and relief of postoperative abdominal pain rate of the two groups were documented and analyzed.Results Three of 31 patients were converted to open surgery.The remaining patients in the two groups were discharged home without any perioperative death.Group A and B were significant differences in the pancreatic ductal incision length (5.0±0.8 vs.6.5±1.0) cm,operation time (289.3±51.6 vs.349.5± 34.7) min,and postoperative hospital stay (8.0± 1.2 vs.10.2± 1.6) d between the two groups (P＜0.05).There were no significant differences in the intraoperative conversion to open rate,intraoperative blood loss,postoperative pancreatic fistula rate,residual stone rate and relief of postoperative abdominal pain rate between the two groups (P ＞ 0.05).Conclusions It was safe and feasible to treat chronic pancreatitis complicated with pancreatolithiasis by laparoscopy.Laparoscopy combined with holmium laser had the added advantages of easy access through the pancreaticojejunostomy,shorter operation time,and less intraoperative blood loss.

Objective To look into the effect of ubiquitin (Ub) in muscles of gastric cancer patients on their nutritional status and prognosis.Methods Abdominal rectus muscles of 102 patients with gastric cancer and 53 patients with benign abdominal diseases were studied.The expressions of Ub mRNA and protein were assessed through real time-PCR and Western blot.Results The relative expression of Ub mRNA in rectus abdominis muscles of gastric cancer patients (4.10± 1.04) was significantly upregulated compared with the control group (3.17±0.32) (t =7.386,P=0.000).The expression of Ub protein in rectus abdominis muscles of patients with gastric cancer was upregulated compared with the controls (0.151 ±0.058 vs.0.084±0.046,t =7.275,P =0.000).The high expression of Ub mRNA in rectus abdominis muscles of gastric cancer patients was significantly associated with decreases in weight,body mass index,prognostic nutritional index,serum albumin and hemoglobin (x2 =11.780,6.557,11.849,15.742,8.360;P=0.001,0.010,0.001,0.000,0.004).The high expression of Ub mRNA in rectus abdominis muscles of gastric cancer patients was not correlated with the patients'sex,age,tumor size or Borrmann type (x2 =0.038,1.978,0.486,1.483;P=0.774,0.160,0.486,0.223),but it was related to the pathologic type,lymph node metastasis and TNM staging of gastric carcinoma (x2 =11.260,9.362,20.517;P=0.004,0.002,0.000).The survival rate of gastric cancer patients with high expression of Ub mRNA was lower than those with low expression (x2 =5.775,P =0.016).Conclusions Ub mRNA and protein were upregulated in rectus abdominis muscles of gastric cancer patients.The high expression of Ub mRNA in these patients was related to their nutritional status and prognosis,which might play an important role in the development of cachexia.