OBJECTIVE To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects. METHODS RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The in vitro release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）] were investigated. The in vivo tissue distribution and gastrointestinal retention [labeled with 11-chloro-1， 1′-dipropyl-3， 3， 3′， 3′-tetramethyl-10， 12- trimethyleneindotricarbocyanine iodide （IR780）] were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated. RESULTS RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67± 8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption peak and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62± 0.38）% ， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX（almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU- LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （P＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（P＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（P＜0.01）. CONCLUSIONS RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

OBJECTIVE To investigate the effect of polymorphisms of solute carrier organic anion transporter family, member 1B3(SLCO1B3) gene on the pharmacodynamics of mycophenolate mofetil(MMF) in patients with lupus nephritis. METHODS Patients with lupus nephritis who were treated in Jieyang People’s Hospital from September 2019 to April 2021 were selected. All subjects were treated with MMF for at least 12 months, or discontinued due to poor efficacy. The efficacy of MMF was evaluated. The SLCO1B3 334T>G/699G>A(rs4149117/rs7311358) genotype was detected using Agena MassARRAY®, and the correlation between gene polymorphisms and MMF pharmacodynamics was analyzed using SPSS 25.0 software. RESULTS The genotype frequencies of SLCO1B3 334T>G/699G>A were in Hardy-Weinberg equilibrium. The probability of poor MMF treatment effect of 334GG/699AA carriers was significantly higher than that of 334TT/699AA and 334TG/699GA carriers(P<0.001); Logistic regression showed that both 334GG/699AA and urine protein>2.5 g·(24 h)−1 were the risk factors for poor MMF treatment[OR=4.038(1.731, 9.420), P<0.001; OR=4.157(1.705, 10.137), P=0.002]. Combined analysis showed that patients with both 334GG/699AA genotype and urine protein>2.5 g·(24 h)−1 were at higher risk for poor efficacy[OR=8.563(3.301, 22.216), P<0.001]. CONCLUSION SLCO1B3 334T>G/699G>A is related to the efficacy of MMF treating lupus nephritis, and 334GG/699AA carriers are more likely to result in poor efficacy.

Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.

Mucinous adenocarcinoma of the renal pelvis is rare in clinical practice. This article reported a case of primary renal pelvis mucinous adenocarcinoma mixed with signet ring cell carcinoma. The patient was admitted to hospital due to right low back pain, and was diagnosed with right kidney stones accompanied by hydrops and infection, right kidney abscess, and nonfunctional right kidney after complete examination. Right renal puncture drainage was performed twice, followed by laparoscopic robot assisted right neprectomy. The postoperative pathological diagnosis was right renal pelvis primary mucinous adenocarcinoma (mixed with signet-ring cell carcinoma). Eleven months after the operation, regular "sodium folinate + oxaliplatin + 5-fluorouracil" chemotherapy was performed for 12 courses, and imaging showed no signs of recurrence or metastasis.

Objective:To explore the effect of multidisciplinary management combined with 60-second high-risk diabetic foot screening in diabetic foot.Methods:From January to December 2022, 138 patients with diabetic foot were selected from Xinxiang Central Hospital by convenience sampling. The patients were randomly divided into a control group and an observation group, with 69 cases in each group. Control group implemented routine follow-up management of diabetic foot, and observation group carried out multidisciplinary management combined with 60-second high-risk diabetic foot screening on the basis of control group, and the intervention lasted for six months. The progress of Wagner grading of diabetic foot and foot self-care were compared between the two groups.Results:After intervention, the number of Wagner grading progression patients in observation group and control group was four cases (5.80%) and 10 cases (14.49%), respectively. The number of progression patients in observation group was less than that in control group, and the difference was statistically significant (χ 2=4.161, P=0.041). The total score and dimension scores of diabetic foot self-management in the two groups after the intervention were higher than those before the intervention, but only the scores of observation group before and after the intervention were statistically significant ( P<0.05). After intervention, the total score and dimension scores of diabetic foot self-management in observation group were higher than those in control group, with a statistically significant difference ( P<0.05) . Conclusions:Multidisciplinary management combined with 60-second high-risk diabetic foot screening can effectively delay the progress of diabetic foot and improve patients' foot self-care.

Objective To explore the clinical efficacy of the arthroscopic"Three Suture-Trident Star"technique in treating avulsion fractures of the distal point of the anterior cruciate ligament(ACL).Meth-ods A retrospective analysis was conducted on 46 patients undergoing the arthroscopic"Three Suture-Trident Star"technique for ACL distal point avulsion fractures between January 2019 and January 2022.The physical examinations(including stability and mobility),International Knee Documentation Committee(IKDC)scores,Tegner activity level scores,visual analogue scale(VAS)scores,postopera-tive satisfaction,complications,and return-to-sports time were compared among before the operation,as well as 6 and 12 months after the operation,respectively.Results The average age of the 46 pa-tients,26 male and 20 female,was 37.6±10.3 years.Their average follow-up period was 14.4±2.7 months.The IKDC scores before surgery and at 6 and 12 months postoperatively were 59.7±5.4,86.1±5.7,and 89.5±5.0(P<0.001),respectively,the corresponding Lysholm scores,Tegner scores and VAS scores were 56.7±5.0,84.8±4.4 and 90.6±4.2(P<0.001),0.5±0.3,4.6±1.7 and 6.6±2.1(P<0.001),as well as 7.1±1.1,1.7±1.0 and 0.7±0.8(P<0.001),respectively.Postoper-ative satisfaction was rated as excellent in 42 cases,good in 3 cases,and fair in 1,with a good-to-excellent rate of 97.8%.The physical examinations at 6 and 12 months postoperatively were of nega-tive results in the anterior drawer and Lachman tests,while the average return-to-sports time was 8.3±2.5 months.All patients had primary healing of the avulsion fractures without any postoperative com-plications such as infection,joint stiffness,displacement or loosening of the fracture block,or mal-union,and none required secondary surgery.Conclusion The arthroscopic"Three Suture-Trident Star"technique demonstrates significant clinical efficacy in treating patients with avulsion fractures of the ACL distal point,effectively restoring postoperative joint stability and function.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective To explore the effects of individual or combination medication of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)combined with chemotherapy on progres-sion-free survival(PFS)in advanced non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutation.Methods A total of 110 advanced NSCLC patients with EGFR mutation in our hospital from January 2019 to April 2021 were selected as research objects.Ac-cording to different therapeutic plans,they were divided into group A with 37 cases(anlotinib chemo-therapy),group B with 32 cases(icotinib chemotherapy)and group C with 41 cases(anlotinib plus icotinib and chemotherapy).The short-term effect,levels of vascular growth factors before and after treatment,and the incidence of adverse reactions were compared among the three groups.After 2 years of follow-up,survival curve was drawn by Kaplan-Meier method,and survival rate and PFS were compared in three groups by Log-rank.Results The objective response rate(ORR)was 68.29％in the group C,which was significantly higher than 43.24％in the group A and 40.62％in the group B(P＜0.05);after treatment,levels of serum vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF)and platelet-derived growth factor(PDGF)in the group C were significantly lower than those in the group A and the group B(P＜0.05);the total incidence of adverse reac-tions was 29.27％in the group C,which showed no significant differences when compared to 24.32％in the group A and 25.00％in the group B(P＞0.05).By the time of the last follow-up,the 2-year overall survival rate was 74.29％in the group C,which was significantly higher than 51.09％in the group A and 45.03％in the group B(Log-rank x2=6.478,P=0.039);the medi-an PFS in the group A,the group B and the group C was 9.0,8.6 and 13.2 months respectively,and differences were statistically significant(Log-rank x2=6.264,P=0.043).Conclusion For the advanced NSCLC patients with EGFR mutations,combination medication of EGFR-TKI com-bined with chemotherapy can effectively increase ORR,reduce levels of serum vascular growth fac-tors,prolong the PFS,and the safety is good.

Objective To explore the effects of individual or combination medication of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)combined with chemotherapy on progres-sion-free survival(PFS)in advanced non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutation.Methods A total of 110 advanced NSCLC patients with EGFR mutation in our hospital from January 2019 to April 2021 were selected as research objects.Ac-cording to different therapeutic plans,they were divided into group A with 37 cases(anlotinib chemo-therapy),group B with 32 cases(icotinib chemotherapy)and group C with 41 cases(anlotinib plus icotinib and chemotherapy).The short-term effect,levels of vascular growth factors before and after treatment,and the incidence of adverse reactions were compared among the three groups.After 2 years of follow-up,survival curve was drawn by Kaplan-Meier method,and survival rate and PFS were compared in three groups by Log-rank.Results The objective response rate(ORR)was 68.29％in the group C,which was significantly higher than 43.24％in the group A and 40.62％in the group B(P＜0.05);after treatment,levels of serum vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF)and platelet-derived growth factor(PDGF)in the group C were significantly lower than those in the group A and the group B(P＜0.05);the total incidence of adverse reac-tions was 29.27％in the group C,which showed no significant differences when compared to 24.32％in the group A and 25.00％in the group B(P＞0.05).By the time of the last follow-up,the 2-year overall survival rate was 74.29％in the group C,which was significantly higher than 51.09％in the group A and 45.03％in the group B(Log-rank x2=6.478,P=0.039);the medi-an PFS in the group A,the group B and the group C was 9.0,8.6 and 13.2 months respectively,and differences were statistically significant(Log-rank x2=6.264,P=0.043).Conclusion For the advanced NSCLC patients with EGFR mutations,combination medication of EGFR-TKI com-bined with chemotherapy can effectively increase ORR,reduce levels of serum vascular growth fac-tors,prolong the PFS,and the safety is good.