AIM: To prepare a nanodrug MMC-ATS-@PLGA using polylactic acid hydroxyacetic acid copolymer(PLGA)as a carrier and mitomycin C(MMC)loaded on PLGA, and to analyse the biological safety and treatment effect of this nanodrug on inhibiting the proliferation of filtering bleb scarring after glaucoma surgery in vivo.METHODS: The thin-film dispersion hydration ultrasonic method was used to prepare the MMC-ATS-@PLGA, and its physical and chemical properties were detected. The effect of MMC-ATS@PLGA on rabbit corneas was analysed through corneal fluorescence staining and HE staining, and tear film rupture time(BUT), Schirmer test and intraocular pressure data were collected to analyse ocular surface biosafety. A slit lamp was used to observe and calculate the filtration bubble size, and the tissue morphological changes were analysed by conjunctival HE staining. In addition, immunohistochemistry and Elisa were used to compare the anti-inflammatory effects of Flumiolone Eye Drops(FML), MMC, and MMC-ATS-@PLGA nanoparticles on inhibiting the formation of filtering bleb scarring after glaucoma surgery from multiple perspectives via comparative proteomic analysis.RESULTS: The average particle size and zeta potential of MMC-ATS-@PLGA were 128.78±2.54 nm and 36.49±4.25 mV, respectively, with an encapsulation efficiency and a drug loading rate of(78.49±2.75)% and(30.86±1.84)%, respectively. At 33°C(the ocular surface temperature), the cumulative release rate of the MMC-ATS-@PLGA nanoparticles reached(76.58±2.68)% after 600 min. Moreover, corneal fluorescence staining, HE, BUT, Schirmer, and intraocular pressure results showed that MMC-ATS-@PLGA had good biocompatibility with the ocular surface of rabbits. At 3 wk after surgery, the area of filtering blebs in the MMC-ATS-@PLGA group was significantly larger than that in the FML group and MMC group, and the filtering blebs in the control group had basically disappeared. Pathological tissue analysis of the conjunctiva in the filtering blebs area of the eyes of the rabbits revealed that compared with that in the normal group, the morphology of the collagen fibres in the MMC-ATS-@PLGA group was relatively regular, the fibres were arranged neatly, and the tissue morphology was similar to that of the normal group. Immunohistochemistry and Elisa confirmed that compared with those in the normal group, the expression levels of α-SMA, CTGF, and type Ⅲ collagen fibre antibodies were significantly increased in the control group. After FML, MMC, or MMC-ATS-@PLGA treatment for 3 wk, the expression of inflammatory factors gradually decreased. Among the groups, the MMC-ATS-@PLGA group showed the most significant decrease(P<0.05).CONCLUSION: This study successfully synthesized a nanomedicine(MMC-ATS-@PLGA)that inhibits scar proliferation after glaucoma filtration surgery. The drug had stable physicochemical properties, good biocompatibility, and better anti-inflammatory effects by inhibiting the expression of α-SMA, CTGF, and type Ⅲ collagen fibres, which can prevent the formation of scarring in the filtering blebs area, thereby improving the success rate of glaucoma filtering surgery.

OBJECTIVE To estimate the cost-utility of sacituzumab govitecan （SG） versus single-agent chemotherapy in the treatment of hormone receptor-positive （HR+）/human epidermal growth factor receptor 2-negative （HER2－） advanced metastatic breast cancer. METHODS From the perspective of the Chinese medical system， a three-state partitioned survival model was constructed to examine the cost-utility of SG versus single-agent chemotherapy based on TROPiCS-02 trial. The cycle length was set to 1 month， and the time horizon was 10 years. The annual discount was 5%. The model output included total costs and quality adjusted life month （QALM）， and incremental cost-effectiveness ratio （ICER） was calculated for cost-utility analysis， by setting willingness-to-pay （WTP） threshold at 3 times gross domestic product （GDP） per capita of China in 2023 （22 340 yuan/QALM）. Univariate sensitivity analyses， probability sensitivity analyses， and scenario analyses were performed to evaluate the robustness of the results and calculate the price threshold when SG had economic advantages. RESULTS SG group gained incremental 4.25 QALM and 561 570 yuan compared with single-agent chemotherapy， which resulted in an ICER of 132 102/QALM that was higher than WTP. The results of the univariate sensitivity analysis showed that the monthly average cost of SG had the greatest impact on the results； the results of probability sensitivity analysis showed that the probability of SG scheme being cost-effective at the WTP threshold was 0. The results of scenario analysis showed that the conclusions of this study were robust under different time horizons （5， 10， 15 years）. The price threshold for SG being cost-effective was 1 344 yuan per 180 mg. CONCLUSIONS Based on the perspective of Chinese medical system， SG appears to be not cost-effective compared with single-agent chemotherapy for HR+/ HER2－ advanced metastatic breast cancer at the price of 8 400 yuan per 180 mg. A substantial price cut should be taken to be cost- effective.

OBJECTIVE To explore the pharmacodynamic related substances and mechanism of Weining San(WNS) against gastric ulcer(GU) according to fingerprint and network pharmacology. METHODS Twelve batches of WNS fingerprints were established by HPLC, and methodological investigation was carried out. Combined with reference substances, characteristic peaks were identified, pharmacodynamic related substances were screened, and network pharmacological analysis was carried out. Using TCMIP and Swiss Target Prediction database to retrieve component targets; Using OMIM, GeneCards and Drugbank databases to retrieve GU disease targets, taking the intersection targets of components and diseases, using String database to construct protein-protein interaction network diagram, and analyzing topological parameters; Using Cytoscape 3.8.2 software to construct "component-disease-target" network diagram; GO and KEGG enrichment analysis of intersection targets were carried out by Metascape website. Then the alcoholic GU mouse model was established by intragastric administration of absolute ethanol to verify the results of network pharmacology prediction. RESUITS　The precision, stability and repeatability of HPLC fingerprint method were good. By comparison and comprehensive analysis of control substances, notoginsenoside R1, ginsenoside Rg1, militarine, ginsenoside Rb1, schisandrin, schisandrol B, deoxyschizandrin and schisantherin A were identified as pharmacodynamic related substances in WNS, which may play their role by regulating core targets such as AKT1, IL-6, STAT3, TNF, IL1B and key signal pathways such as PI3K-Akt and JAK-STAT. The gastric ulcer index, ulcer inhibition rate and HE staining showed that WNS could improve gastric mucosal injury in GU mice. The results of ELISA, WST-1 and TBA showed that WNS could decrease the levels of TNF-α, IL-6, IL-1β and MDA, and increase the levels of SOD and PGE2, suggesting that the anti-GU effect of WNS was related to the inhibition of inflammatory reaction and oxidative stress mechanism, which further verified the prediction of network pharmacology. CONCLUSION This study combines fingerprint analysis, network pharmacology, and animal experimental validation to explore the pharmacodynamic related substances and mechanisms of WNS anti-GU efficacy, providing reference for quality control and clinical research of WNS.

Objective: To simulate the tumor microenvironment though the 3D microtumor model which was constructed using droplet microfluidics.To explore its feasibility as a model for in vitro breast cancer research through3D microtumour fabrication,characterisation and sensitivity testing to chemotherapeutic drugs. Methods: Breast cancer cells were encapsulated with hydrogel shells in collagen-rich microencapsulated cores to obtain breast cancer microtumours in vitro;breast cancer microtumours were co-cultured with 3D microencapsulated endothelial cells by Transwell system.The structure and growth characteristics of the microtumours were directly observed by microscopy;the CCK-8 assay was used to detect the proliferation of the cells under different culture models and the drug sensitivity to doxorubicin;flow cytometry was used to compare the differences in apoptosis during the proliferation process;and the differences in the migratory and invasive abilities of the cells were assessed by scratch assay and Transwell assay;the expression of epithelial-mesenchymal transition-related proteins was detected by Western blot. Results: Breast cancer cells grew well in hydrogel nucleus-shell microcapsules;cell proliferation assays showed that 3D culture and 3D co-culture cells proliferated at a significantly lower rate than 2D culture;3D culture and 3D co-culture cells had enhanced migration and invasion ability and showed higher expression of EMT-related proteins compared to 2D culture;3D culture and 3D co-culture cells were significantly less sensitive to chemotherapeutic drugs compared to 2D culture.The sensitivity of 3D and 3D co-cultured cells to chemotherapeutic drugs was significantly reduced compared to 2D culture. Conclusion 3D cultures show similar morphology and biology to in vivo tumours and are more resistant to chemotherapeutic agents.

OBJECTIVE To investigate the HRCT and MRI characteristic of external auditory canal cholesteatoma(EACC)in children.METHODS A total of 40 patients(45 lesions)with EACC confirmed by pathology were retrospectively analyzed with HRCT and MRI characteristics and clinical therapeutic value.Imaging findings of 40 patients(45 lesions)with EACC were retrospectively analyzed.RESULTS Soft tissues were found in all the external auditory canal(EAC).Of the forty-five soft tissues,7 manifested as inhomogeneous strip soft tissues and 38 as lesions solid soft tissues;30 located in medial part of the EAC and covered the tympanic membrane,while the other 15 presented as tympanic membrane perforation and involved the tympanic cavity.The MRI of the 3 ears showed high signal on T2/T1 iso-intensity,high signal on DWI,and low signal on ADC.Normal whole bony EAC was observed in 17 cases and enlarged medial EAC in 28 cases.Seven cases only involved in the superior wall,but 38 cases displayed as multiple bone wall involved,of which 6 involved in circumferential walls.Thirty-three cases displayed atactic ear bone margin,11 displayed blunted or disappeared drum shield plate.Destroy of long crus of incus and manubrium mallei occurred in 15 cases,of short crus of incus in 8 cases,of stapes in 2 cases,and mastoiditis in 5 cases.According to the pneumatization degree of mastoid air cell,37 cases were classified into pneumatic type,7 cases into mixed type,and the last one into diploic type.CONCLUSION The children EACC tends to be limited and rarely involved in middle ear and mastoid process.No patient with peri-ear infection was found.Application of HRCT and MRI help accurate location and determination of cholesteatoma.According to the extent of the lesion,selecting the appropriate surgical method is an effective method to remove cholesteatoma,improve hearing and reduce recurrence.

Objective:To explore the early predictive value of umbilical cord blood S100β protein and lactate combined with amplitude integrated electroencephalogram（aEEG）in small for gestational age（SGA）preterm infants with brain injury.Methods:One hundred and six cases of SGA preterm infants were enrolled in this study in Neonatology Department of Inner Mongolia People's Hospital from January 2019 to December 2021. Umbilical cord blood serum S100β protein and lactate at birth of All SGA preterm infants were tested，and aEEG was monitored at 6h and 72 h after birth，corrected gestational age of 32 weeks and 37 weeks. According to the diagnostic criteria of brain injury in preterm infants，SGA preterm infants were divided into brain injury group（45 cases）and non-brain injury group（61 cases），and compared the differences of S100β protein，lactate and the designated time aEEG between the two groups.SGA preterm infants with brain injury were further divided into symmetrical group（28 cases）and non-symmetrical group（15 cases）. The differences of umbilical cord blood S100β protein and lactate level between the two groups were compared，and the diagnostic value in different types of SGA preterm infants with brain injury was also compared.Results:SGA preterm infants in the brain injury group had significantly higher levels of umbilical cord blood S100β protein［（0.826±0.218）μg/L vs（0.397±0.196）μg/L， t=8.316， P<0.05］and lactate［（8.5±1.3）mmol/L vs（3.8±0.9）mmol/L， t=3.281， P<0.05］than those in non-brain injury group.Symmetric SGA group had higher level of S100β protein than the asymmetric SGA group［（0.924±0.205）μg/L vs（0.438±0.196）μg/L， t=5.734， P<0.05］.But there was no statistically significant difference in lactate levels［（5.6±1.4）mmol/L vs（3.9±1.2）mmol/L， t=0.932， P>0.05］between symmetric SGA group and asymmetric SGA group. The abnormal rates of aEEG in brain injury group and non-brain injury group were respectively 100%（45/45）vs 22.95%（14/61）at 6 h after birth，95.56%（43/45）vs 16.39%（10/61）at 72 h after birth，62.22%（28/45）vs 6.56%（4/61）at 32 weeks of corrected gestational age，22.22%（10/45）vs 3.28%（2/61）at 37 weeks of corrected gestational age. The abnormal rate of brain injury group was higher than the non-brain injury group in the same nodal time，and the differences were statistically significant（ χ 2 value respectively 62.292，64.913，38.074，9.257，all P<0.05）. Conclusion:There were significant value in umbilical cord blood S100β protein，lactate level and aEEG monitoring in the early diagnosis in preterm infants SGA with brain injury. The combination of the three might be more helpful for the early diagnosis and timely treatment of brain injury in SGA preterm infants.

Objective:To observe of the effects of micro-video breakthrough education and thematic workshops in the care of internal fistulae in maintenance haemodialysis patients, to provide a basis for improving prognosis of patients.Methods:This study was a randomized controlled trial. A total of 90 cases of maintenance haemodialysis patients with endocardial fistula were selected in Huzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine from January to December in 2022 as the observation samples using convenience sampling method. They were divided into the experimental group and the control group with 45 cases in each group by the method of random number table. The control group used the conventional nursing care for maintenance haemodialysis endocardial fistula to administer nursing care, the experimental group introduced the micro-video breakthrough education and thematic workshop as a combined mechanism of intervention. The self-care behaviors with arteriovenous fistula and other observation indexes between the two groups were compared.Results:There were 23 males and 22 females in the control group, aged (58.07 ± 3.00) years old. There were 24 males and 21 females in the experimental group, aged (58.93 ± 4.07) years old. After care, the total internal fistula self-care behaviour score in the experimental group was (49.44 ± 1.84) points, and (38.93 ± 2.19) points in the control group, the difference between the two groups were statistical significant ( t = 24.65, P<0.05). For health management adherence, the score of fluid intake, dialysis regimen, medication and dietary dimension were (15.82 ± 1.37), (12.87 ± 1.39), (17.24 ± 1.33) and (21.60 ± 1.03) points in the experimental group, and (11.20 ± 0.92), (9.98 ± 1.14), (12.11 ± 1.01) and (17.40 ± 1.10) points in the control group, the difference between the two groups were statistical significant ( t values were 10.78 to 20.62, all P<0.05). For positive psychological capital, the scores of self-efficacy, resilience, hope and optimism were (38.69 ± 1.22), (39.27 ± 1.10), (33.29 ± 1.52) and (33.40 ± 1.39) points, and were (31.16 ± 1.26), (31.04 ± 1.15), ( 26.13 ± 1.52) and (27.09 ± 7.28) points in the control group, the difference between the two groups were statistical significant ( t values were 5.71 to 34.77, all P<0.05). The total complication rate of the experimental group was 8.89% (4/45), lower than 28.89% (13/45) in the control group, and the differences were all statistically significant ( χ2 = 5.87, P<0.05). Conclusions:The combined application of micro-video breakthrough education and special workshops in maintenance hemodialysis patients with internal fistula is beneficial to the improvement of their internal fistula self-care ability, health management compliance and positive psychological capital, and can reduce the probability of internal fistula complications.

Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.