【Objective】 To observe the presence of ferroptosis in acute pancreatitis (AP) and the effect of iron ions on the NLRP3 pathway so as to explore the possible mechanisms for the protection of pancreatic alveolar cells. 【Methods】 A total of 45 male C57BL/6 mice were randomly divided into three groups (control, AP, and AP+2′2-bipyridyl). A total of 12 injections (caerulein, 50 μg/kg) were given at one-hour intervals. The AP+2′2-bipyridyl group was pretreated with 2′2-bipyridyl (20 mg/kg) for 1 hour, and then injected with caerulein. The control group was injected with an equal volume of normal saline. All of the mice were killed one hour after the last injection. Their pancreases were harvested for histopathological evaluation, immunohistochemistry analyses, and Western blotting. 【Results】 The ferroptosis inhibitor 2′2-bipyridyl could prevent the accumulation of iron ions, reduce the formation of lipid peroxides and the injury in the process of AP, and it also reduced pancreatic inflammation through NLRP3 pathway. 【Conclusion】 This experiment confirmed the real existence of ferroptosis, a form of cell death, in AP, and revealed that inhibition of ferroptosis can reduce pancreatic inflammatory damage in AP.

Objective:To explore the anti-inflammatory effect and safety of two non-steroidal anti-inflammatory drugs in the phacoemulsification combined with intraocular lens (IOL) implantation.Methods:A randomized, double-blind, clinical trial was conducted.A total of 90 age-related cataract patients (90 eyes) who were diagnosed in Qingdao Eye Hospital Affiliated to Shandong First Medical University were enrolled from October 2020 to February 2021.The patients were randomized to diclofenac sodium group and bromofenac sodium group by random number table method, with 45 cases (45 eyes) in each group.All patients underwent phacoemulsification combined with IOL implantation, and 0.1% diclofenac sodium eye drops (preservative-free), 4 times a day, and 0.1% pramiphene eye drops, 2 times a day were applied in the perioperative period.The duration of continuous medication treatment and follow-up time were 6 weeks.The subjective symptoms of the patients were scored before and after surgery.The amount of tear fluid secretion was detected by Schirmer I test, and the tear film breakup time was recorded with the Oculus dry eye analyzer.Corneal fluorescein staining was observed under a slit lamp microscope with cobalt blue light.Anterior chamber flash was measured by slit-lamp biomicroscopy.The thickness of central macular area and the presence of macular cystoid edema was measured by optical coherence tomography.Visual acuity, noncontact intraocular pressure (IOP) and the drug safety were examined and evaluated.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Qingdao Eye Hospital (No.[2020]60).All patients were informed about the surgery and postoperative medication and signed the informed consent form.Results:All subjects had no intraoperative complications, and completed treatment and follow-up as required.The preoperative, 1-day postoperative, 1-week postoperative, 6-week postoperative subjective symptom scores were (0.47±0.73), (0.56±0.62), (0.33±0.48), and (0.51±0.66) points in the diclofenac group, and (0.47±0.51), (0.75±0.61), (0.64±0.65), and (0.78±0.77) points in the bromfenac group.There were statistically significant differences in the subjective symptom scores at different time points between the two groups ( Fgroup=5.001, P=0.028; Ftime=2.920, P=0.035), and the subjective symptom scores of diclofenac sodium group were significantly lower than those of bromofenac sodium group (all at P<0.05).The preoperative, 1-week postoperative, 6-week postoperative tear secretion volume were (5.87±2.37), (6.07±2.53), and (6.29±0.25) mm in diclofenac sodium group, and (7.36±2.74), (6.29±3.46), and (5.80±2.76) mm in bromofenac sodium group.There was statistically significant difference in the tear secretion volume between the two groups before surgery ( F=6.910, P=0.012), but there was no significant difference on postoperative weeks 1 and 6 ( F=1.121, 0.772; P=0.729, 0.384).The preoperative, 1-week postoperative, 6-week postoperative non-invasive tear break-up time (NIBUT) were (8.00±6.28), (6.68±5.24), and (6.17±5.00) seconds in diclofenac sodium group, and (6.40±5.28), (4.50±2.46), and (5.39±5.39) seconds in bromofenac sodium group.There was no significant difference in NIBUT between the two groups ( Fgroup=3.415, P=0.068).There was significant difference in NIBUT within groups among different time points ( Ftime=4.358, P=0.020).The 1-day postoperative, 1-week postoperative, 6-week postoperative corneal epithelial staining score were (1.40±0.81), (0.13±0.34), (0.00±0.00) points in diclofenac sodium group, and (1.38±0.89), (0.22±0.47), and (0.00±0.00) points in bromofenac sodium group.There was no statistically significant difference in the corneal epithelial staining score between the two groups after surgery ( Fgroup=0.110, P=0.741).There were statistically significant differences in corneal epithelial staining scores within groups among different time points ( Ftime=175.054, P<0.01).The 1-day postoperative, 1-week postoperative, 6-week postoperative anterior chamber flare classification were 1.13±0.51, 0.13±0.34, and 0.00±0.00 in diclofenac sodium group, and 1.02±0.34, 0.16±0.37, and 0.00±0.00 in bromofenac sodium group.There was no significant difference in the overall anterior chamber flash between the two groups ( Fgroup=0.045, P=0.507).There were statistically significant differences in anterior chamber flash within groups among different time points ( Ftime=322.331, P<0.001).There was no significant difference in the preoperative and 6-week postoperative macular fovea thickness between both groups ( t=-0.221, -0.374; both at P>0.05).The incidence of macular cystoid edema 6 weeks after operation was 0% in both groups.Subjects tolerated the two tested drugs well.Eight adverse events occurred in this study, all of which were mild postoperative IOP elevation, including 3 in diclofenac sodium group with an incidence of 6.67% and 5 in bromofenac group with an incidence of 11.1%.IOP returned to normal in all the patients 1 week after stopping the use of drug. Conclusions:Two nonsteroidal anti-inflammatory drugs are safe and effective for anti-inflammatory treatment after cataract phacoemulsification combined with IOL implantation.The new diclofenac sodium eye drops are more comfortable than bromfenac sodium eye drops.

Objective To characterize the distribution of conjunctival sac flora and antibiotic susceptibility in healthy people of different ages.Methods Totally 1 839 conjunctival sac secretion samples from 1 131 people without infectious eye diseases attending Qingdao Eye Hospital of Shandong First Medical University from 2018 to 2021 were retrospectively analyzed.These people were divided into four groups according to age:children(≤18 years old),young(19-45 years old),middle-aged(46-65 years old),and elderly(＞65 years old).Differences in the distribution of conjunctival sac flo-ra and antibiotic susceptibility among these groups were compared using the chi-square test or Fisher's exact test.The Bonferroni method was used for pairwise comparisons.Results The total bacterial detection rate of the conjunctival sac in the study population aged 1 month to 91 years old(median:11.00 years old;quartiles:5.00 years old,40.00 years old)was 64.93％;the bacterial detection rate in the children group(76.79％)was significantly higher than that in the young,middle-aged and elderly groups(all P＜0.001).Staphylococcus epidermidis(55.97％),Staphylococcus aureus(8.60％)and Streptococcus mitis(7.52％)were the most common bacteria in the conjunctival sacs.Gram-positive bacteria were re-sistant to most penicillins(16.79％-53.47％)and macrolides(17.21％-20.87％)antibiotics,and highly susceptive to van-comycin(99.56％)and gatifloxacin(98.57％).Gram-negative bacteria had low susceptibility rates to cephalosporin(41.38％-80.00％)antibiotics and were susceptive to amikacin(90.48％)and fluoroquinolone(90.91％-97.73％)antibi-otics.Of the common antibiotics used in ophthalmology,the susceptibility rate of fusidic acid was the worst in the children group(54.55％),which was significantly lower than the other three groups(all P＜0.001).Gatifloxacin had a susceptibili-ty rate of more than 90％in different Gram-stained bacteria in all groups,with an overall sensitivity rate of 98.44％.Con-clusion Staphylococcus epidermidis is the most common bacteria in the conjunctival sac in healthy people of all ages.Gatifloxacin is generally susceptive in different Gram-stained bacteria in people at different ages,and may be considered as the first choice for perioperative empiric antibiotics in ophthalmology.

Objective To explore the early clinical efficacy of 3D printing technology-assisted customized prosthesis with preservation of femoral condyles for the reconstruction of bone defects after resection of distal femoral malignancies.Methods From June 2019 to September 2021,our department determined the lesion range of 12 cases of malignant tumors in the distal femur through CT and MRI before surgery.We used computer-aided production of osteotomy guide plates and customized prostheses that preserved the femoral condyle.After the prostheses were customized,the tumor segment was removed and a reconstruction was performed by using the customized prosthesis with preservation of femoral condyles.The knee function was evaluated by the American Musculoskeletal Tumor Society(MSTS)functional evaluation criteria.Results The operative time was 180-270 min,with a mean of 200 min.The intraoperative bleeding was 300-800 ml,with a mean of 450 ml.A total of 12 cases were followed up for 12-50 months(average,21.9 months).Two patients died of lung metastasis at 12 and 16 months after surgery,one patient survived with lung metastasis at 3 months after surgery,and one patient(8.3%)developed periprosthetic infection at 1 year after surgery.In 10 patients,imaging showed that the prosthesis and plate were in a good position without signs of loosening or bone resorption,the proximal femur was fixed in place with the 3D printed collar,and continuous bone scab formation was found in 4 cases.At the final follow-up,the functional status of the affected limb was good,with the knee flexion of 105°-135°(mean,115°)and no limitation of extension.The MSTS score was 22-28 points[mean,(24.3±1.8)points].Conclusion Application of 3D printing-assisted customized prosthetic replacement technology with preservation of the femoral condyles allows for precise resection of malignant distal femoral tumors and effective anatomical reconstruction without increasing surgical trauma and risk,significantly improving postoperative limb function and potentially reducing long-term complications.

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

Objective:To investigate the effects of ursolic acid (UA) on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure.Methods:Sixty healthy female SD rats were randomly divided into five groups: normal control group (NC group), PM2.5 unexposed AR group (AR group), PM2.5 exposed AR group (ARE group), UA intervention AR group (AR+UA group), and UA intervention PM2.5 exposed AR group (ARE+UA group), with 12 rats in each group. AR model was performed by a basal sensitization with intraperitoneal injection of ovalbumin (OVA) and followed by nasal instillation. PM2.5 exposure was carried out by inhalation exposure system at a concentration of 200 μg/m 3 for 3 h/d for 30 days. UA intervention group was given UA intragastric administration at 20 mg/(kg·d). AR symptoms including sneezing, nasal scratching and nasal secretion of rats in each group were observed. The activities of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in nasal mucosa were tested. The pathological changes of nasal mucosa were observed by HE staining. The levels of OVA-sIgE, IL-6 and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Protein microarray was used to measure the expression of multiple inflammation cell factors in nasal mucosa. Statistical analysis was performed with SPSS 20.0. Results:After UA intervention, the frequency of nasal sneezing, scratching and nasal secretion in ARE+UA group were lower than those of ARE group ( P<0.05). Pathological examination of nasal mucosa showed that ARE+UA group had less inflammatory granulocyte infiltration and less pathological damage to the epithelial layer than ARE group. The activities of SOD in nasal mucosa of ARE+UA group were higher than those of ARE group ((50.10±3.09) U/mg vs (20.13±1.30) U/mg, F value was 597.54, P<0.01). The contents of MDA in nasal mucosa of ARE+UA group were lower than those of ARE group ((57.78±12.36) nmol/g vs (124.12±9.40) nmol/g, F value was 115.51, P<0.01). The expression levels of OVA-sIgE, IL-6 and IL-17 proteins were lower in the ARE+UA group than those in ARE group ((11.61±0.27) ng/ml vs (20.30±0.67) ng/ml, (47.59±15.49) pg/ml vs (98.83±10.98) pg/ml, (623.30±8.75) pg/ml vs (913.32±9.06) pg/ml, F value was 283.42, 80.45, 683.73, respectively, all P<0.01). After UA intervention, protein microarray analysis showed that the expression of IL-4, IL-6, IL-13, chemokine CXCL7, IL-1α, IL-1β, MMP-8 and MCP-1 in ARE+UA group was decreased compared with ARE group while IFN-γ and IL-10 increased (all P<0.01). Conclusion:UA can reduce the aggravated AR symptoms and pathological damage of nasal mucosa, inhibit oxidative stress and release of inflammatory factors after PM2.5 exposure, and thus plays a protective role in the pathological damage of AR induced by PM2.5 exposure.

Objective:To investigate the effect of licochalcone A on osteoarthritis in rats and its relationship with p38-MAPK inflammatory signaling pathway.Methods:A total of 160 male Wistar rats were randomly divided into blank non-intervention, blank intervention, arthritis non- intervention and arthritis intervention groups with 40 rats in each group. Rats in the arthritis groups were subjected to unilateral anterior cruciate ligament transection, while rats in the blank groups were only subjected to skin incision and suture. Rats in the intervention groups were treated by intra-articular injection of 1 mL 10 μmol/L licochalcone A for 8 successive weeks. Eight weeks later, the cartilage of rats in each group was stained with safranin, and osteoarthritis soft tissue was scored according to Osteoarthritis Research Society International guideline under the optical microscope. The cartilage was cultured in low glucose cell culture medium supplemented with 5% fetal bovine serum for 48 hours. The contents of nitric oxide, prostaglandin E 2, sulfated glycosaminoglycan and collagen II in the medium were determined by the chemiluminescence reaction method. The expression levels of p38, phosphorylated p38 (p-p38) and matrix metalloproteinase in cartilage tissue were detected by western blot assay. Results:The progress of osteoarthritis in rats treated with licochalcone A was slow. The Osteoarthritis Research Society International score in the arthritis intervention group was significantly lower than that in the arthritis non-intervention group [(3.8 ± 1.7) points vs. (9.7 ± 1.2) points, P = 0.0064]. The contents of nitric oxide, prostaglandin E 2, sulfated glycosaminoglycan, and collagen II in the arthritis intervention group were (77.84 ± 17.65) μmol/mg and (6.78 ± 1.76) ng/mg, (89.78 ± 9.76) μg/mg, and (1.78 ± 0.76) μg/mg, respectively, which were significantly lower than those in the arthritis non-intervention group [(107.56 ± 18.74) μmol/mg, (10.756 ± 1.87) ng/mg, (125.75 ± 8.87) μg/mg, (3.76 ± 0.88) μg/mg, (NO: P = 0.002; PGE 2: P < 0.001; sGAG: P < 0.001; Collagen II: P < 0.001). Western blot assay results revealed that the relative expression of p38, p-p38, p-p38 to total p38 ratio, matrix metalloproteinase in the arthritis intervention group were (3 454 ± 421), (2 072 ± 175), (0.65 ± 0.14 )and (1 776 ± 765), respectively, which were significantly lower than those in the arthritis non-intervention group (5 322 ± 323), (4 257 ± 184), (0.89 ± 0.11), (3 865 ± 874)( p38: P < 0.001; p-p38: P < 0.001; p-p38/p38: P = 0.002; MMP: P = 0.001). Conclusion:Licochalcone A can delay the progression of osteoarthritis in rats with osteoarthritis through inhibiting inflammatory reaction and cartilage matrix degradation, and p38-MAPK signaling pathway may be involved in the regulation process.

Objective: To understand the current situation and associated factors of myopia among primary school students, and to provide scientific basis for prevention and control of myopia among primary school students. Methods: In Gansu, Guangdong, Guangxi, Guizhou, Liaoning, Shandong, Shanxi and other provinces, 1 prefecture was selected, and a number of primary schools were selected from each region. All the students in the class were selected as the object of this survey. A total of 8 365 middle school students were examined for their eyesight, and the data of general population economic indicators and natural environment indicators were obtained through the statistical yearbook of various provinces and cities. The influencing factors of primary school students myopia were analyzed by chi-square test and multivariate Logistic regression. Results: Univariate analysis showed that different provinces and different sex, different nationalities, different grade, parents average salary, sunshine duration, air temperature, altitude, longitude, latitude, different economic zone(χ2=116.22, 18.08, 26.33, 1 059.04, 14.86, 10.28, 16.95, 10.01, 23.15, 29.43, 88.14, P<0.05). Multivariate analysis results showed that gender, grade, sunshine duration, longitude were risk factor for poor vision(OR=1.31, 1.71, 1.45, 1.54, P<0.05); Economic zone and parents salary were protective factors for poor eyesight of students (OR=0.65, 0.86, P<0.05). Conclusion Myopia of primary school students is affected by a variety of factors, economic and social factors and natural environmental factors have an impact on the screening.

Objective: To understand the current situation and associated factors of myopia in junior middle school students, and to provide scientific basis for prevention and control of myopia in junior middle school students. Methods: A total of 5 393 junior middle school students were selected from middle schools in Guangdong, Guangxi, Guizhou, Liaoning, Shandong, Shanxi provinces. The visual acuity of middle school students was examined, and the data of general population, economy, sociology and natural environment were obtained through statistical yearbook of each province. The influencing factors of myopia of middle school students were analyzed by univariate and multivariate Logistic regression. Results: The results of single factor analysis showed that the myopia rate of junior high school students was different by gender, grades, parents average wage, sunshine duration, temperature, altitude, longitude and latitude(χ2=47.76，59.05，10.79，106.19，53.56，85.02，76.23，107.07，P<0.05). The results of multi factor analysis showed that gender, grade, average wage, temperature and latitude was positively associated with myopia vision; sunshine duration and longitude were negatively associated with the risk for myopia(OR=1.54，1.34，1.62，7.58，27.10，0.42，0.39，P<0.05). Conclusion The myopia of junior high school students is affected by a variety of factors, economic and social factors and natural environmental factors have an impact on the screening of sexual myopia in junior high school students. Economic and social factors and natural environmental factors should be taken into account in the formulation of myopia prevention and control measures.

Objective: To investigate the possible pathogenesis of Staphylococcus aureus (S.aureus) corneal ulcer by analyzing the differentially expressed genes (DEGs) of S.aureus isolated from the patients with corneal ulcer and healthy conjunctival sac. Methods: Ten strains of S.aureus isolates were obtained from January to August 2018 in the clinical laboratory of Qingdao Eye Hospital.Five strains of S.aureus isolated from patients with corneal ulcer and five strains of S.aureus isolated from healthy conjunctival sac were included.The gene expression profiles of 10 strains of S.aureus were sequenced by Illumina high-throughput RNA-sequencing (RNA-Seq). P≤0.05 and fold change≥2 were used as the threshold to determine the statistically DEGs.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to determine the biological functions of DEGs. Results: The genome-wide transcriptional analysis demonstrated that 270 genes were differentially expressed with 138 upregulated genes and 132 downregulated genes in the strains from corneal ulcer.Function analysis of DEGs revealed that genes encoding alpha hemolysin, delta hemolysin, virulence factor EsxA and LysR family transcriptional regulators were significantly upregulated in strains isolated from cornea ulcer.GO enrichment analysis showed that most DEGs was involved in the metabolic process with the biosynthesis, the most significantly related process was the metabolism of inosine monophosphate.The KEGG pathways suggested that a number of metabolic pathways had significant changes, such as S.aureus infection, two-component system and pyruvate metabolism, purine metabolism, which were critical to the pathogenesis of S.aureus corneal ulcer. Conclusions Identification of the DEGs between corneal ulcer isolates and healthy conjunctival isolates of S.aureus is helpful for further investigations on genes or pathways associated with the pathogenesis and therapeutic targets of S.aureus corneal ulcer.