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.

The gut microbiota is a vast microbial ecosystem,specifically present in the organism and plays an important regulatory role in the body's health or disease state together with its metabolites.After spinal cord injury,the complex pathophysiology at the site of trauma makes axonal regeneration difficult,and the autonomic motor dysfunction induced by spinal cord injury disrupts gastrointestinal function and causes gut microbiota imbalance.The previous clinical outcomes of neurorepair strategies after spinal cord injury have not been ideal.The dysregulated gut microbiota and neuroinflammation after spinal cord injury are closely associated with the prognosis of the patients.The potential mechanisms by which the gut microbiota may influence the neuroinflammation after spinal cord injury may include the activation of gut-associated lymphoid tissue and disruption of the intestinal barrier by the imbalanced microbiota,and gut microbiota and its metabolites such as lipopolysaccharides(LPS),short chain fatty acids(SCFAs),5-hydroxytryptamine(5-HT),and tryptophan,as well as immune cells,inflammatory factors,and neurotransmitters the local inflammatory response in the spinal cord through the circulatory system.This paper revews the studies on the changes in gut microbiota after spinal cord injury and their effects on the spinal cord neuroinflammation,providing new targets and new ideas for improving the neuroinflammation after spinal cord injury.

Objective:To evaluate the short-term rehabilitation effect of wearable visual training devices based on extended reality (XR) glasses in patients after macular hole surgery.Methods:A self-controlled study was conducted.Eleven patients with monocular low vision after macular hole surgery were recruited at Renmin Hospital of Wuhan University from October 2022 to March 2024.All patients underwent biofeedback training for 3 months using the independently developed visual rehabilitation training glasses LOOKBON T10.The LogMAR best corrected visual acuity (BCVA), retinal sensitivity, effective fixation rate, fixation stability, reading speed, vertical metamorphopsia (MV), horizontal metamorphopsia (MH), and Chinese version of the visual-related quality of life assessment form (CVRQoL-25) were compared before and after training.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2024-K263).Written informed consent was obtained from each subject.Results:After training, the patients' BCVA, retinal sensitivity, effective fixation rate, fixation stability, and reading speed were 0.69±0.19, (21.61±2.75)db, (92.43±4.06)%, (93.09±4.31)%, and (104.82±21.85) characters/minute, respectively, which were significantly improved compared to 0.85±0.28, (17.71±3.17)db, (31.83±19.05)%, (32.35±19.12)%, and (69.64±20.17) characters/minute before training ( t=5.253, -5.987, -11.561, -12.003, -11.682; all at P<0.001).After training, MV and MH were (0.29±0.20)° and (0.21±0.24)°, respectively, which were significantly reduced compared to pre-training (0.44±0.24)° and (0.43±0.41)° ( t=9.238, 4.068; both at P<0.01).After training, the CVRQoL-25 score was 1 193.18±229.43, which was significantly higher than pre-training 947.73±203.86 ( t=-11.687, P<0.001). Conclusions:The application of wearable visual training equipment based on XR glasses can effectively improve the visual function of patients with poor visual function recovery after macular hole surgery, and enhance their quality of life.

Objective To systematically analyze influencing factors of migration stress of patients'families transferred out of intensive care unit(ICU)in China,and provide evidence-based guidance for alleviating migration stress level of families of transferred patients.Methods Computer searches were conducted on China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP,China Biomedical Literature Database,Web of Science,PubMed,the Cochrane Library and Embase for observational studies such as cohort studies,case-control studies and cross-sectional studies on factors influencing migration stress among family members of ICU patients.Search deadline was from database establishment to October 2023.Literature screening,quality assessment and data extraction were conducted independently by two researchers in accordance with the inclusion and exclusion criteria.RevMan5.4 software was used to conduct a Meta-analysis of the data results.Results Fifteen studies were finally included,with a total sample size of 2558 and 12 influencing factors were extracted.Fifteen articles were divided into positive scoring group(higher scores,higher levels of migration stress,nine articles)and negative scoring group(higher scores,lower levels of migration stress,six articles)based on instruments used to measure outcome indicators.When analyzing each group,only factors mentioned in the group more than twice were included in Meta analysis.Meta analysis showed that within positive scoring group,family member education level,family member gender,patient awareness,ICU treatment time and family member uncertainty about the disease were factors affecting migration stress of ICU transfer patients'families(P<0.05);In reverse calculation group,educational level of family member,gender of family member,age of patient and ICU treatment time were influencing factors of migration stress of family members of ICU transfer patients(P<0.05).Sensitivity analysis result showed that result of each factor was relatively stable.Conclusion Educational level of family member,gender of family member,age of patient,ICU treatment time,uncertainty of family member's illness are influencing factors of migration stress of family members of patients transferred out of ICU in China.Influence of family member's religious beliefs and patient's consciousness needs further demonstration.

OBJECTIVE To introduce the construction of undergraduate specialty of clinical pharmacy based on the concept of outcome-based education （OBE），and to provide new idea and enlightenment for the construction of undergraduate specialty of clinical pharmacy in Chinese universities. METHODS Through the establishment and construction of training objectives and graduation requirements ，teaching reform was designed and implemented ，and the construction of teaching support system and teaching quality assurance system were completed. RESULTS The clinical pharmacy department of our university established the training direction of clinical pharmacy talents under the guidance of post competence ，including clarifying the training needs of undergraduate talents based on the overall requirements of national undergraduate education ；defining the social and industrial needs of clinical pharmacy talents based on the normative documents or concepts of clinical pharmacy ；clarifying the post and ability needs of clinical pharmacy talents based on the investigation of graduates and clinical pharmacists ；clarifying the development needs of clinical pharmacy based on the current situation and trends at home and abroad ；forming characteristic training objectives combined with the regional characteristics and school positioning ， so as to construct training objectives and graduation requirements. The OBE concept was introduced into the undergraduate teaching reform of clinical pharmacy ；the pharmacy talent training direction were established under the guidance of post competence ；the training system was designed by reverse design method；a training mode of both innovation and practical ability was built so as to promote teaching reform ，strengthen the construction of grass-roots teaching organizations and teaching staff ， and improve the construction of teaching quality assurance system. CONCLUSIONS The undergraduate training mode of clinical pharmacy specialty based on the concept of OBE is helpful to improve students ’personal comprehensive quality and professional knowledge and skills. The established undergraduate training model of clinical pharmacy specialty is in line with the modern educational concept and social needs ，and provides theoretical basis and practical experience for the training mode of clinical pharmacy professionals.

Pigs are considered as ideal donors for xenotransplantation because they have many physiological and anatomical characteristics similar to human beings. However, antibody-mediated immunity, which includes both natural and induced antibody responses, is a major challenge for the success of pig-to-primate xenotransplantation. Various genetic modification methods help to tailor pigs to be appropriate donors for xenotransplantation. In this study, we applied transcription activator-like effector nuclease (TALEN) to knock out the porcine α-1, 3-galactosyltransferase gene GGTA1, which encodes Gal epitopes that induce hyperacute immune rejection in pig-to-human xenotransplantation. Meanwhile, human leukocyte antigen-G5 gene HLA-G5, which acts as an immunosuppressive factor, was co-transfected with TALEN into porcine fetal fibroblasts. The cell colonies of GGTA1 biallelic knockout with positive transgene for HLA-G5 were chosen as nuclear donors to generate genetic modified piglets through a single round of somatic cell nuclear transfer. As a result, we successfully obtained 20 modified piglets that were positive for GGTA1 knockout (GTKO) and half of them expressed the HLA-G5 protein. Gal epitopes on the cell membrane of GTKO/HLA-G5 piglets were completely absent. Western blotting and immunofluorescence showed that HLA-G5 was expressed in the modified piglets. Functionally, the fibroblasts from the GTKO/HLA-G5 piglets showed enhanced resistance to complement-mediated lysis ability compared with those from GTKO-only or wild-type pigs. These results indicate that the GTKO/HLA-G5 pigs could be a valuable donor model to facilitate laboratory studies and clinics for xenotransplantation.
Animals ; Animals, Genetically Modified ; Gene Knockout Techniques ; HLA Antigens ; Humans ; Nuclear Transfer Techniques ; Swine ; Transplantation, Heterologous

Objective: To investigate the AIDS-related knowledge, attitudes and practice among university students in a pilot site of AIDS health education in Zhoushan City, so as to provide the reference for AIDS health education in universities. Methods: University students were recruited from Zhejiang Ocean University using a stratified cluster sampling method in 2018 and 2020, and the AIDS-related knowledge, attitudes and practice were collected using a questionnaire survey. Results: A total of 2 862 and 2 850 students were surveyed in 2018 and 2020, including 1 429 ( 49.93% ) and 1 414 ( 49.61% ) male students, respectively. The overall awareness of AIDS-related knowledge was 86.62% and 94.11% in 2018 and 2020, respectively. There were 544 ( 19.01% ) and 394 ( 13.82% ) students that were in favor of one-night stand, 308 ( 10.76% ) and 198 ( 6.95% ) students that were in favor of commercial sexual behaviors, and there were 59 ( 2.06% ) and 34 ( 1.19% ) students that had casual sexual behaviors within one year, and 20 ( 0.70% ) and 8 students ( 0.28% ) with commercial sexual behaviors within one year. There was a significant difference in the awareness of AIDS-related knowledge among students with different years at the university ( P<0.05 ). The lowest awareness of AIDS-related knowledge was seen in freshmen in 2018 ( 81.74% ), and the highest awareness was found in freshmen in 2020 (97.17% ). The proportions of being in favor of one-night stand ( 2018: 31.35% vs. 6.70%; 2020: 22.07% vs. 5.71%; P<0.05 ), being in favor of commercial sexual behaviors ( 2018: 19.91% vs. 2.23%; 2020: 12.09% vs. 1.88%; P<0.05), having casual sexual behaviors within one year (2018: 3.71% vs. 0.42%; 2020: 2.19% vs. 0.21%; P<0.05), and having commercial sexual behaviors within one year ( 2018: 1.33% vs. 0.07%; 2020: 0.50% vs. 0.07%; P<0.05 ) were significantly greater in male students than in female students. Conclusions The pilot AIDS health education is effective to increase the awareness of AIDS-related knowledge, possess the correct attitudes towards sexual behaviors and reduce high-risk sex behaviors among university students in Zhoushan City. Intensified AIDS health education is recommended among senior and male university students.

Toll-like receptor 3 (TLR3), as an important pattern recognition receptor (PRR), dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases. Atherosclerosis is proved as an inflammatory disease, and inflammatory events involved in the entire process of initiation and deterioration. However, the contribution of TLR3 to atherosclerosis remains unclear. Herein, we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis. Besides, activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules. Conversely, silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation. Given the aberrance in TLR3 functions on atherosclerosis progression, we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy. Therefore, we developed the novel ellipticine derivative SMU-CX24, which specifically inhibited TLR3 (IC₅₀ = 18.87 ± 2.21 nmol/L). In vivo, atherosclerotic burden was alleviated in Western diet fed ApoE^-/- mice in response to SMU-CX24 treatment, accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion. Thus, for the first time, we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression, thereby proposing a new strategy and probe for atherosclerosis therapy.

Objective:To evaluate the effect of preoperative cognitive behavioral therapy (CBT) on pain catastrophizing in the patients with orthopedic trauma.Methods:A total of 120 patients with lower extremity bone trauma, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18-28 kg/m 2, with Pain Catastrophic Scale (PCS) score on admission >16, scheduled for surgical treatment, were enrolled.The patients were divided into 2 groups ( n=60 each) by the stratified randomization method based on the type of fracture: CBT group and routine group (group R). Group CBT received CBT for pain through the internet on the day of admission and one day before operation.The patients in both groups underwent reduction and internal fixation of lower extremity fractures under combined spinal-epidural anesthesia.The PCS scores were recorded immediately after admission and on the morning of the operation day.The effective pressing times of the patient-controlled analgesia pump, consumption of analgesics for rescue analgesia, and occurrence of nausea and vomiting within 48 h after operation were recorded.The visual analogue scale score of the surgical site during activity and occurrence of the score >3 at 3 months after operation and use of opioids within 3 months after operation were recorded. Results:Compared with group R, the PCS score was significantly decreased on the morning of the operation day, the pressing times of the patient-controlled analgesia pump, consumption of analgesics for rescue analgesia and incidence of nausea and vomiting within 48 h after operation were decreased, the requirement for opioids within 3 months after operation was decreased ( P<0.05), and no significant change was found in VAS score during activity and occurrence of the score >3 at 3 months after operation in group CBT ( P>0.05). Conclusions:Preoperative CBT can reduce the degree of pain catastrophizing and is helpful in increasing the quality of postoperative analgesia in the patients with orthopedic trauma.