Dry eye,also known as keratoconjunctivitis sicca,is clinically manifested as dry eyes,itching,burning,blurred vision and other symptoms,which seriously affects the life quality of patients.In recent years,the incidence of dry eye has increased year by year,and it has become one of the common clinical diseases in ophthalmology.At present,the treatment methods of dry eye mainly include drug treatment,surgical treatment and clinical nursing,among which drug is the most commonly used method for the treatment of dry eye.Therefore,this paper summarizes the application and research progress of clinical medication of dry eye based on permeation pathways and inflammatory pathways in recent years,so as to provide some ideas for the follow-up treatment of dry eye and drug development.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Objective:To study the feasibility and safety of percutaneous jejunal drainage in treatment of hepatolithiasis after choledochojejunostomy.Methods:The clinical data of 24 patients with hepatolithiasis after choledochojejunostomy treated by percutaneous jejunal drainage at the Cholelithiasis Center, Shanghai East Hospital Affiliated to Tongji University from May 2021 to May 2022 were retrospectively analyzed. There were 16 males and 8 females, aged (50.46±10.89) years old. Ultrasound and X ray guided percutaneous jejunography was performed under local anesthesia for patients with hepatolithiasis after choledochojejunostomy. Then the fistula was directly dilated to 16.0Fr, and percutaneous jejunal choledochoscopy was performed 3 days later. The success rate, complication rate and stone removal rate were analysed.Results:Twenty-four patients were treated with percutaneous jejunography, with a success rate of 79.2%(19/24), including 19 patients after anterior colonic cholangiojejunostomy with a success rate of 94.7%(18/19), and 5 patients after retrocolonic cholangiojejunostomy with a success rate of 20.0%(1/5). There was no complication including bleeding, intestinal leakage and bile leakage. In 19 patients with successful percutaneous jejunography, the success rate of fistula dilation was 100%(19/19), and there was no complication. Five patients with failed percutaneous jejunography underwent open choledocholithotomy through the jejunal output-loop, and bile leakage occurred in one patient. Thirteen patients with anastomotic stenosis, 5 with intrahepatic biliary strictures, and 6 with anastomotic and intrahepatic biliary strictures were diagnosed by choledochoscopy and selective cholangiography in these 24 patients. After choledochoscopic electrotomy, cylindrical balloon dilation, stone removal, stenting and other treatments, the stenosis relief rate was 100%(24/24), and the clearance rate of intrahepatic bile duct stones was 91.7%(22/24).Conclusion:Percutaneous jejunal drainage was a feasible, safe and minimally invasive method for treatment of hepatolithiasis after choledochojejunostomy. The procedure was especially suitable for patients with anterior colonic cholangiojejunostomy.

Objective:To screen the time points of high survival rate and efferocytosis dysfunction of rat alveolar macrophages stimulated by cigarette smoke extract (CSE), establish an in vitro model of alveolar macrophage efferocytosis function, and study chronic respiratory diseases with chronic inflammatory reaction as the main pathological changes. Methods:① Time point screening experiment: rat alveolar macrophages (NR8383 cells) were cultured in vitro, and the cells in logarithmic growth phase were divided into blank control group (100 μL complete medium) and 5% CSE group (90 μL complete medium + 10 μL 100% CSE). Alma blue method was used to detect the effect of 5% CSE on the activity of NR8383 cells at 6, 12, 24 and 48 hours. ② Apoptosis induction experiment: rat type Ⅱ alveolar epithelial cells (RLE-6TN cells) were cultured in vitro as phagocytic target cells of NR8383 cells, and the cells in logarithmic growth phase were divided into blank control group and 10, 30 and 60 minutes groups after ultraviolet exposure (apoptosis was induced by 30 000 μJ/cm 2 ultraviolet irradiation for 15 minutes). Flow cytometry was used to detect the apoptosis rate of RLE-6TN cells cultured for 10, 30 and 60 minutes after ultraviolet exposure. ③ Cell efferocytosis experiment: NR8383 cells in logarithmic phase were divided into blank control group and 5% CSE group. Two hours before NR8383 cells were stimulated by CSE for 6, 12 and 24 hours, RLE-6TN cells were exposed to ultraviolet to induce apoptosis, and the RLE-6TN cell suspension was added to NR8383 cells (the ratio of RLE-6TN cells to NR8383 cells was 5∶1). Flow cytometry was used to detect the efferocytosis rate of NR8383 cells to RLE-6TN cells at different time points treated with 5% CSE. Results:① Compared with the blank control group, the activity of NR8383 cells significantly decreased after treatment with 5% CSE for 48 hours [cell reduction rate: (68.5±4.1)% vs. (73.6±2.3)%, P < 0.05]. However, there were no significant differences when the activities of NR8383 cells treated with 5% CSE for 6, 12 and 24 hours were compared with the blank control group, so these three time points were selected for the subsequent establishment of alveolar macrophage cell efferocytosis dysfunction in vitro model experiment. ② Compared with the blank control group, the apoptosis rate of RLE-6TN cells significantly increased at 10, 30 and 60 minutes after ultraviolet exposure [(66.87±8.63)%, (85.51±2.39)%, (96.13±2.74)% vs. (9.13±3.17)%, all P < 0.01] in a time-dependent manner. Considering that it taked about 50 minutes for RLE-6TN cells to be labeled with PKH26 membrane labeling probe, 10 minutes after ultraviolet exposure was selected to label RLE-6TN cells. ③ Compared with the blank control group, the efferocytosis function of NR8383 cells was significantly decreased after treatment with 5% CSE for 12 hours [cell efferocytosis rate: (33.64±1.30)% vs. (44.02±2.71)%, P < 0.01], but there was no significant effect on the efferocytosis function of NR8383 cells at 6 hours and 24 hours. Conclusions:CSE can induce alveolar macrophage cell efferocytosis dysfunction. Based on the test results of the effect of 5% CSE on NR8383 cell activity and cell efferocytosis function, 12 hours with high survival rate and weak efferocytosis effect of NR8383 cells can be selected as the in vitro model condition of alveolar macrophage cell efferocytosis dysfunction.

Objective: To explore the treatment technique, occurrence and development patterns of such radiation injuries as in a major radiological accident in which a victim suffered mild bone marrow radiation sickness combined grade degree Ⅲ acute radiation induced skin injury, based on his dose estimation, clinical manifestations and disease treatments. Methods: History inquiry in detail, earlier physical dose estimation and biological dose estimation were conducted in conjunction with analyzing the chromosome aberration of peripheral blood lymphocytes. The physical dose was estimated by Monte Carlo method.The systematic laboratory and imaging examination was performed to evaluate the condition. The comprehensive analysis was conducted to determine the diagnosis and treatment plan. Results: At 3d after the exposure, "Ren" felt mild pain and discomfortable on the skin of the right index finger. The body of the right hand index finger was covered with blister at 21 d after exposure.The estimation of biological dose was 0.43 Gy (95%CI: 0.31-0.58 Gy), and the physical dose was estimated to be 36-164 Gy for each part of the right hand finger. The hematopoietic system, immune system and endocrine system were normal. The liver function index value was transiently increased. The liver damage resulted from the use of antibiotic-induced combined with the patient′s past medical history and admission examination result, and the relevant antibiotics were discontinued. The liver function returned to normal after liver protection treatment. At 22 d after irradiation, a right finger incision and decompression surgery were performed. The stem cells were extracted and implanted into the right index finger. After 59 days of hospitalization, there was no obvious discomfort in the body, and the right index finger recovered well, as well as the pain significantly relieved, and the knuckle activity was basically normal. Conclusions The patient with excessive radiation and grade Ⅲ acute radiation skin injury was successfully treated, and local application of autologous adipose-derived stem cell transplantation achieved good result .

As one of the top three causes of death in the world, chronic obstructive pulmonary disease (COPD) is a serious hazard to human health. Macrophages play an important role in COPD, and their efferocytosis function is essential for ending chronic inflammation of COPD. Efferocytosis damage of alveolar macrophages (AM) in patients with COPD causes the rising of bacterial infection and airway bacterial colonization risk in lungs, which is the main reason for the acute exacerbation and the rising of incidence rate and mortality rate in COPD. In recent years, the regulation of macrophage efferocytosis function in COPD has becoming a research hotspot. Progress on the role of macrophage efferocytosis function on COPD, and the breakthrough points of improving AM efferocytosis dysfunction by traditional Chinese medicine is reviewed, so as to provide new ideas for the prevention and treatment of COPD.

Objective To investigate the late effects induced by ionizing radiation and the rehabilitation treatment of local radiation injury by medical follow-up of the patient exposed to192 Ir at 5.7 accident in Nanjing,and to provide more experience for the treatments in the medical emergency of nuclear or radiological accident.Methods According to the history inquiry and physical examination of the patient in detail and the record of clinical symptoms and signs,the changes of the blood system,immune system,reproductive system,eyes,nervous system were systematically evaluated.The effects of rehabilitation treatment for the patient with lower limb dysfunction were also assessed.Results After the medical treatments of the patient,the hematopoietic immune system was restored,but the bone marrow aspiration still showed low bone marrow hyperplasia in right ilium.Meanwhile,the level of sex hormones was within the normal range,but semen examination showed sperm motility was 0.The radiation damage also occurred in the eye lens,retina and fundus.Howevcr,the psychological evaluation showed that the patient was stable and the right lower limb skin wound healing was well except for dysfunction and pain in some extent,which was relieved after the rehabilitation treatment.Conclusions The physiological function of the exposed victim with mild bone marrow type acute radiation sickness could be completely or partially restored after the clinical treatment in the early stage.

Objective To evaluate the therapeutic efficacy of stereotactic body radiotherapy (SBRT) with gamma knife on stage Ⅰ-Ⅱ non-small-cell lung cancer(NSCLC)and the quality of life of the patients undergoing this therapy.Methods Twenty NSCLC patients with the median age of 76,10 at stage Ⅰ and 10 at stage Ⅱ who were unable or unwilling to undergo surgery were given SBRT with gamma knife at the doses of 3-6 Gy in 8-15 fractions,finished within 2 to 3 weeks.The prescription isodose line was 50％,the marginal dose was 39-56 Gy,the central dose was 78-112 Gy,and the total biologically effective dose was 51-83 Gy.The patients were observed after admission and followed up by chest CT 1,3,6,and 12 months after treatment until progressive disease or death.EORTC QLQ-LC43 questionnaire was used to investigate the changes in quality of life.Results The 20 patients were followed up for 24 (12-46) months.At six months after the treatment,the overall response rate was 80％,and the complete response rate was 35％.The 1,2 and 3-year local control rates were 100％,95％ and 95％,respectively.The 1,2 and 3-year overall survival rates were 95％,80％ and 50％ respectively; The 1,2,and 3-year progression free survival rates were 85％,64％ and 33％,respectively.The failure rate was 20％ and the rate of progress within the planning target volume was 5％.No acute toxicity at grade 3 and over occurred in any patient during the treatment.15％ of the patients developed grade 1-2 radiation pneumonia.Age,gender,pathologic index or not were weakly correlated with the overall survival.The emotional function was improved significantly after treatment (P ＜ 0.05),dyspnea and cough were improved at different degrees,however,not significantly.There were no significant changes in the physical function and symptoms,such as fatigue,lack of appetite,insomnia,etc.Conclusions Significantly improving the motional function and maintaining the quality of life,SBRT with gamma knife is effective for elderly NSCLC patients with high local control rate fair overall survival rate and few side effects.

Based on the biomechanical response of human knee joint to a front impact in occupants accidents, a finite element (FE) model of human knee joint was developed by using computer simulation technique for impacting. The model consists of human anatomical structure, including femoral condyle, tibia condyle, fibular small head, patellar, cartilage, meniscus and primary ligament. By comparing the results of the FE model with experiments of the knee joint in axial load conditions, the validation of the model was verified. Furthermore, this study provides data for the mechanical of human knee joint injury, and is helpful for the design and optimization of the vehicle protective devices.
Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Knee Injuries ; physiopathology ; Knee Joint ; anatomy & histology ; physiology ; Models, Anatomic ; Models, Biological

Objective To analyze the efficacy and prognosis of stereotactic radiotherapy (SRT) and whole-brain radiotherapy (WBRT) in treatment of brain metastases,and to observe the influence of temozolomide (TMZ) on survival rate during the period of radiotherapy.Methods A total of 52 patients with brain metastases were divided into two groups according to treatment methods,including 35 patients treated with WBRT plus SRT and 17 patients treated with SRT alone.WBRT dose was 1.8 - 3.0 Gy per fraction,one fraction a day,five fractions per week,with total dose of 30 - 40 Gy.After WBRT,gamma knife was performed with prescription isodose line of 45％ -70％ surrounding the planned target volume in WBRT + SRT group.The marginal dose was 12 - 15 Gy and the center dose was 20-30 Gy.In SRT group,the prescription isodosc line was 45％ - 70％ and the marginal dose was 36 - 40 Gy while the center up to 70 - 80 Gy.The follow up time was 1 - 2 years.Besides 20 patients in this study took temozolomide capsule during and after radiotherapy.The schedule of concomitant chemotherapy was temozolomide of 75 mg/m2 by oral administration every day until radiotherapy was over,and then temozolomide of 150 mg/m2 was taken for 3 -6 months after radiotherapy.Results The efficiency during 1 -3 months after treatment was 84.62％ in this study.In the WBRT + SRT group,the efficiency was 88.57％ and declined to 76.47％ in the SRT group.The six month-and one year-local control rate were 92.10％ and 85.20％,respectively.The average survival time of WBRT + SRT was 13.2 months and median survival time was 11 months.Six month-,one year-and eighteen months-survival rate were 71.40％,54.30％ and 14.30％,respectively.In the SRT group,the average survival time was 10.2 months and median survival time was 9 months.Six month-,one year- and eighteen month-survival rate were 41.20％,23.50％ and 5.88％,respectively,while those for RT + TMZ group were 80.00％,60.00％ and 10.00％.In comparison,those in RT group were 56.30％,37.50％ and 12.50％,respectively.Conclusions Effect of gamma knife stereotactic radiotherapy combined with WBRT is better than GK stereotactic radiotherapy alone in treatment of brain metastases.Compared with radiotherapy alone,concomitant temozolomide chemotherapy could improve the survival rate of the patients with brain metastases without increasirg adverse reactions significantly.