AIM:To evaluate the clinical efficacy of 0.05% cyclosporine eye drops(Ⅱ)combined with sodium hyaluronate eye drops in treating patients with type 2 diabetes mellitus(T2DM)and moderate-to-severe dry eye.METHODS:A total of 120 T2DM patients(120 eyes)with moderate-to-severe dry eye, treated at the endocrinology and ophthalmology departments at the Affiliated Hospital of Xuzhou Medical University from January 2024 to September 2024, were enrolled in the study. The patients were randomly divided into two groups: combination group [0.05% cyclosporine eye drops(Ⅱ)+ sodium hyaluronate eye drops] and control group(sodium hyaluronate eye drops alone), with 60 cases(60 eyes)in each group. Assessments were conducted at baseline and at 1, 2, and 3 mo post-treatment, including the ocular surface disease index(OSDI), non-contact tear meniscus height(NITMH), first non-invasive tear breakup time(NIBUTf), meibomian gland loss score, lipid layer thickness grade, conjunctival hyperemia grade, and corneal fluorescein staining(FL)score. At 3 mo after treatment, changes in tear inflammatory factors were observed, and corneal subbasal nerve plexus(SBN)morphology/density were analyzed using in vivo confocal microscopy(IVCM).RESULTS:At 1, 2, and 3 mo post-treatment, both groups showed statistically significant increases in NITMH and NIBUTf compared to baseline(all P<0.05), with greater improvement observed in the combination group(both P<0.05). OSDI and FL scores significantly decreased from baseline(all P<0.05), with more pronounced reductions in the combination group(both P<0.05). Meibomian gland loss scores showed no significant improvement in either group(all P>0.05). At 3 mo after treatment, tear levels of interleukin 6(IL-6)and matrix metalloproteinase-9(MMP-9)significantly decreased in both groups(all P<0.001), with a greater reduction noted in the combination group(both P<0.001). The combination group displayed increased corneal nerve branch density and nerve fiber density, along with decreased nerve tortuosity and dendritic cell(DC)density compared to baseline(all P<0.001), while the control group did not show significant changes(all P>0.05).CONCLUSION: The combination of 0.05% cyclosporine eye drops(Ⅱ)and sodium hyaluronate eye drops significantly improves clinical outcomes in T2DM patients with moderate-to-severe dry eye. This treatment effectively alleviates ocular surface inflammation, restores corneal nerve morphology and density, and demonstrates a favorable safety profile.

AIM: To explore the risk factors associated with diabetic retinopathy(DR)based on ultra-widefield swept-source optical coherence tomography angiography(UWF-SS-OCTA), and to establish a clinical prediction model.METHODS:A total of 235 patients(235 eyes)with type 2 diabetes mellitus who were treated in the Affiliated Hospital of Xuzhou Medical University from July to November 2024 were selected as the research objects. According to the presence or absence of DR, they were divided into 120 cases(120 eyes)in non-DR group(NDR group)and 115 cases(115 eyes)in non-proliferative DR group(NPDR group). Data on general characteristics, laboratory tests, and OCTA results were collected for both groups. Univariate analysis was employed to identify DR-related risk factors. Logistic regression analysis was conducted to analyze these risk factors and to establish a DR prediction model. The efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve, calibration curve, and decision curve analysis(DCA).RESULTS: The duration of diabetes, fasting blood glucose, blood urea nitrogen(BUN), history of hypertension, and the choroidal vascular index(CVI)were found to be statistically significant in the model(all P<0.05). Specifically, the duration of diabetes, fasting blood glucose, BUN, and history of hypertension were identified as risk factors for DR among diabetic patients, while CVI was recognized as a protective factor. The area under the curve for the model predicting the probability of DR was 0.898(0.859-0.938), with a diagnostic threshold of 0.438. The corresponding sensitivity and specificity were 87.8% and 78.3%, respectively, indicating that the model possesses high predictive value for the occurrence of DR.CONCLUSION: The duration of diabetes, fasting blood glucose, BUN, history of hypertension, and CVI are significantly correlated with DR. The established prediction model demonstrates a substantial screening capability for DR.

BACKGROUND:It has been proved clinically that adhesion of fibrous scar with the dura mater or nerve root after lumbar operation is an important factor for postoperative symptoms,such as postoperative pain and numbness. OBJECTIVE:To verify the inhibitory effect of autologous ligamentum flavum on the formation of epidural fibrous scar after lumbar surgery and explore the possible molecular biological mechanism. METHODS:Forty-eight Japanese white rabbits(6-8 months old)were randomly divided into three groups:a ligamentum flavum preservation group,a ligamentum flavum non-preservation group,and an autologous fat reposition group.A lumbar laminectomy model was established in all the three groups of rabbits,and rabbit epidural tissues were collected at 3 and 6 weeks after modeling.Hematoxylin-eosin staining was used to observe histological changes and the number and density of fibroblasts,VG staining was used to observe the percentage of collagen fiber area,and immunohistochemistry was used to observe the expression of transforming growth factor β1 and Smad3 proteins. RESULTS AND CONCLUSION:Hematoxylin-eosin staining results revealed that fibroblasts in the ligamentum flavum preservation group were few and loosely arranged,while the cells in the ligamentum flavum non-preservation and autologous fat reposition groups were more numerous and closely arranged.The number density of fibroblasts in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P＜0.05);however,there was no significant difference between the latter two groups.VG staining results showed that the collagen fibers in the ligamentum flavum preservation group were sparse and distributed unevenly,while a lot of red collagen fibers were gathered in the ligamentum flavum non-preservation and autologous fat reposition groups.The area percentage of collagen fibers in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P＜0.05),but there was no significant difference between the latter two groups.The results of immunohistochemistry showed that the degree of positive staining of retained histone the ligamentum flavum preservation group was significantly lower than that of the other two groups.The absorbance value of transforming growth factor β1 and Smad3 in the ligamentum flavum preservation group was significantly lower than that in the other two groups at 3 and 6 weeks after surgery(P＜0.05),but there was no significant difference between the latter two groups.To conclude,there are different degrees of epidural fibrous scar formation after lumbar surgery.If the ligamentum flavum is preserved,it can help to reduce the number of epidural fibroblasts as well as the formation of collagen fibers,thus reducing the adhesion of the fibrous scar tissue to the dural sac and nerve root.The mechanism is not only a purely mechanical blockade,but also to reduce the formation of epidural fibrous scar by interfering with the transforming growth factor β1/Smad3 signaling pathway.

Selenium is one of the essential trace elements in human body, which plays an important role in regulating human growth and physiological function. Selenium deficiency can lead to a variety of diseases, such as Kashin-Beck disease, Keshan disease, thyroid disease and increase the incidence of cancer. It was found that serum selenium level decreased significantly in patients with leukemia, and it was associated with poor prognosis. Selenium can play a dual role in the treatment of leukemia: on the one hand, it can play a synergistic anti-leukemia effect with chemotherapy drugs, and on the other hand, it can reduce the side effects of chemotherapy drugs. In recent years, nano-selenium, as a new type of elemental selenium, has higher bioavailability, stronger bioactivity and lower toxicity than organic and inorganic selenium. This article reviews the progress of selenium and its compounds in leukemia.

Objective To analyze the relationship between angiotensin type Ⅱ 1 receptor autoantibodies (AT1-AA),blood uric acid and urea nitrogen with hypertensive disorder complicating pregnancy (HDCP). Methods A total of 125 patients with HDCP diagnosed in the obstetrics department of Tianjin Municipal Bao-di District People's Hospital from August 2021 to February 2023 were randomly selected as the HDCP group, and 55 healthy pregnant women admitted to this hospital during the same period were selected as the control group.The HDCP group was divided into the gestational hypertension subgroup (n=77) and preeclampsia group (n=48) according to the degree of disease progression.The levels of serum uric acid,blood urea nitro-gen and AT1-AA were detected and compared between the HDCP group and control group and between the gestational hypertension subgroup and preeclampsia subgroup.Results There were no statistically significant differences in the age,gestational time,D-dimer,serum calcium and serum creatinine between the control group and the HDCP group (P>0.05).The levels of peripheral blood AT1-AA,serum uric acid and blood u-rea nitrogen in the HDCP group were higher than those in the control group,and the differences were statisti-cally significant (P<0.05).The levels of peripheral blood AT1-AA,serum uric acid and blood urea nitrogen in the preeclampsia subgroup were significantly higher than those in the gestational hypertension subgroup, and the differences were statistically significant (P<0.05).The Spearman rank correlation coefficient analysis showed that the levels of peripheral blood AT1-AA (r=0.301),serum uric acid (r=0.380) and blood urea nitrogen (r=0.257) levels were positively correlated with the severity degree of HDCP (P<0.01).The area under the curve (AUC) of AT1-AA,serum uric acid and blood urea nitrogen detection alone and combined de-tection in the diagnosis of HDCP were 0.680,0.714,0.647 and 0.725,and the corresponding Youden coeffi-cients were 0.368,0.380,0.306 and 0.439,indicating that the value of combined testing was higher than that of single item detection in the diagnosis of HDCP.Conclusion AT1-AA,serum uric acid and blood urea nitro-gen are correlated with the occurrence and development of HDCP,and the 3-item combined detection has high-er value.

Objective To study the inhibitory activities of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives against the entry of SARS-CoV-2 into host cells.Methods With pentacyclic triterpene saponin glycyrrhizic acid(a natural SARS-CoV-2 entry inhibitor)as the lead compound,a series of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives were designed and synthesized based on hypridization principle,and their inhibitory activities against virus entry were tested in SARS-CoV-2 pseudovirus-infected cells.The antiviral targets of the lead compound 1b was identified by pseudotyped SARS-CoV-2 infection assay and surface plasmon resonance(SPR)assay,and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of 1b on virus-cell membrane fusion.Molecular docking and single amino acid mutagenesis were carried out to analyze the effect of 1b on binding activitiy of S protein.Results The lead compound 1b showed significant inhibitory effect against Omicron pseudovirus with an EC50 value of 3.28μmol/L(P<0.05),and had broad-spectrum antiviral activity against other SARS-CoV-2 pseudovirus.Spike-dependent cell-cell fusion assay demonstrated an inhibitory effect of 1b against SARS-CoV-2 S protein-mediated cell-cell fusion.Molecular docking analysis predicted that the lead compound 1b could be well fitted into a cavity between the attachment(S1)and fusion(S2)subunits at the 3-fold axis,where it formed multiple hydrophobic interactions with Glu309,Ser305,Arg765 and Lys964 residues with a KD value of-8.6 kcal/mol.The compound 1b at 10,5,2.5 and 1.25 μmol/L showed a significantly reduced inhibitory activity against the pseudovirus with mutated Arg765,Lys964,Glu309 and Leu303(P<0.01).Conclusion 3-O-β-chacotriosyl glycyrrhetinic acid derivatives are capable of stabilizing spike protein in the pre-fusion step to interfere with the fusion of SARS-CoV-2 with host cell membrane,and can thus serve as potential novel small-molecule SARS-CoV-2 fusion inhibitors.

Objective To study the inhibitory activities of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives against the entry of SARS-CoV-2 into host cells.Methods With pentacyclic triterpene saponin glycyrrhizic acid(a natural SARS-CoV-2 entry inhibitor)as the lead compound,a series of 3-O-β-chacotriosyl glycyrrhetinic acid derivatives were designed and synthesized based on hypridization principle,and their inhibitory activities against virus entry were tested in SARS-CoV-2 pseudovirus-infected cells.The antiviral targets of the lead compound 1b was identified by pseudotyped SARS-CoV-2 infection assay and surface plasmon resonance(SPR)assay,and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of 1b on virus-cell membrane fusion.Molecular docking and single amino acid mutagenesis were carried out to analyze the effect of 1b on binding activitiy of S protein.Results The lead compound 1b showed significant inhibitory effect against Omicron pseudovirus with an EC50 value of 3.28μmol/L(P<0.05),and had broad-spectrum antiviral activity against other SARS-CoV-2 pseudovirus.Spike-dependent cell-cell fusion assay demonstrated an inhibitory effect of 1b against SARS-CoV-2 S protein-mediated cell-cell fusion.Molecular docking analysis predicted that the lead compound 1b could be well fitted into a cavity between the attachment(S1)and fusion(S2)subunits at the 3-fold axis,where it formed multiple hydrophobic interactions with Glu309,Ser305,Arg765 and Lys964 residues with a KD value of-8.6 kcal/mol.The compound 1b at 10,5,2.5 and 1.25 μmol/L showed a significantly reduced inhibitory activity against the pseudovirus with mutated Arg765,Lys964,Glu309 and Leu303(P<0.01).Conclusion 3-O-β-chacotriosyl glycyrrhetinic acid derivatives are capable of stabilizing spike protein in the pre-fusion step to interfere with the fusion of SARS-CoV-2 with host cell membrane,and can thus serve as potential novel small-molecule SARS-CoV-2 fusion inhibitors.

The Mayo Clinic in the United States is a non-profit medical institution that integrates clinical practice, education, and research. It has maintained a global top hospital brand image for a long time and its management ideas have been widely recognized and appreciated by the industry. From the perspective of strategic management, this study elaborated on the core values of Mayo Clinic, the multidisciplinary team cooperation diagnosis and treatment model, the high fixed salary salary system, the management model of doctor leadership-operation supervisor cooperation, the business mission of integrated clinical practice, education, and research, and the management points of digital marketing, which could provide references for the high-quality development and brand building of hospitals in China.

Objective The family reconstruction method was used to establish paternity index algorithm for uncle-nephew relationships between two full sibling uncles and one nephew.Methods According to Mendelian genetic law,the family of two known full-sib uncles and one nephew were reconstructed according to the relationship between uncle and nephew,and the test hypothesis was established between two full sibling uncles and one nephew as the uncle-nephew relationship and unrelated individuals,and the paternity index of the uncle-nephew relationship between two full sibling uncles and one nephew was calculated by using Excel.Results Among the 99 genotypic combinations between two full sibling uncles and one nephew,91 of which were consistent with the genetic rules of uncle-nephew relationships,while 8 of which were not.a stepwise mutation model was introduced in the situations that do not conform to the genetic laws of uncle-nephew relationships.The paternity index of uncle-nephew relationship between two full sibling uncles and one nephew can be calculated using Excel.Conclusion The uncle-nephew testing involved by two full sibling uncles makes use of the role of the assistant,and the paternity index of the obtained uncle-nephew relationship is higher than that between two known full-siblings alone and their nephew,which has a good practical value in helping the appraiser to draw a clear appraisal opinion.

Objectives:To evaluate the preoperative prediction methods of osteotomy angle of thoracolumbar kyphosis in ankylosing spondylitis(AS)patients,and to analyze their clinical values in reconstruction of spinopelvic sagittal alignment.Methods:22 AS patients with thoracolumbar kyphosis,who underwent single segment pedicle subtraction osteotomy(PSO)from January 2015 to January 2022 in the First Affiliated Hospital of Xinjiang Medical University,were retrospectively reviewed.There were 17 males and 5 females with a mean age of 44.3±7.4 years(range,29-56 years).Preoperative and postoperative spinopelvic parameters were measured on X-ray lateral radiographs,osteotomy angles were predicted with different methods,full balance integated index(FBI),spine femoral angle(SFA),hilus pulmonis-hip axis(HP-HA),center of both acoustic meati-hip axis(CAM-HA),and Surgimap method.And theoretical spinopelvic parameters and theoretical os-teotomy angle were calculated according to pelvic incidence(PI).The differences between preoperative,final follow-up and theoretical spinopelvic parameters,and between the predictive,actual and theoretical osteotomy angles,were compared.Results:The osteotomy sites of the 22 cases included 4 in L1,10 in L2 and 8 in L3.All the patients achieved ideal imaging and surgical results.The differences in pelvic tilt(PT),sacral slope(SS),lumbar lordosis(LL),thoracic kyphosis(TK),thoracolumbar kyphosis(TLK),global kyphosis(GK),and sagittal vertical axis(SVA)between final follow-up and preoperation were statistically significant(P＜0.05).The osteotomy angles predicted with FBI,SFA,HP-HA,CAM-HA,and Surgimap methods were 50.5°±12.1°,52.0°±11.3°,53.9°±8.1°,51.3°±5.8°,and 43.2°±9.2°,respectively,with statistically significant differences(F=2.342,P=0.046).The theoretical osteotomy angle required by simulated osteotomy to restore the ideal spinopelvic sagittal alignment was 51.2°±8.1°,which wasn't statistically different from the osteotomy angles predicted with FBI,SFA,HP-HA or CAM-HA methods(P＞0.05).The actual osteotomy angle during the operation was 41.1°±5.4°,which was statistically different from the osteotomy angles predicted with FBI,SFA,HP-HA and CAM-HA methods(P＜0.05),but not statistically different with the angle predicted with Surgimap method(P＞0.05).Conclusions:The osteotomy angles predicted with FBI,SFA,HP-HA,and CAM-HA methods are similar with the theoretical osteotomy angle,while different from the actual osteotomy angle to some extent;The osteotomy angle predicted with Surgimap method is similar with the actual osteotomy angle.