Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Objective:To investigate the clinical effect of turbocharged large free anterolateral thigh flaps (ALTF) by anastomosis with a superior perforator of the flap in reconstruction of large soft tissue defects of limbs.Methods:From June 2017 to June 2021, 6 patients with large soft tissue defects of limbs with exposed joints and tendons were treated in the Department of Hand and Foot Surgery of the Affiliated Hospital of Qingdao University with turbocharged large free ALTFs. The pressurised blood supply of ALTF was achieved by anastomosing a superior perforating branch carried in the flap. Such large and turbocharged ALTFs were used to repair large soft tissue defects with exposed joints and tendons in limbs. Of the 6 patients, there were 4 males and 2 females, and aged 32-60(46.0±8.1) years old. Cause of injury: 5 by traffic accident and 1 by machine crush. Four patients had soft tissue defects in lower limbs: 2 with open tibia and fibula fractures, 1 had patellar defect and fibula fracture, and 1 associated with fibula fracture. The other 2 patients had soft tissue defect in upper limbs with bone and tendon exposed but without fracture. The sizes of wound were 25.0 cm×12.0 cm-35.0 cm×19.0 cm. In the primary surgery, Vacuum sealing drainage (VSD) was applied. In the second stage, free ALTFs were used to cover the wound. The area of flap incision was increased by anastomosing the superior perforators and as the consequence, the size of flaps was achieved to 26.0 cm×13.0 cm-36.0 cm×15.0 cm. Donor site of 6 cases were reduced by direct suture, and the remaining wound was covered by free skin graft. Postoperative follow-ups were conducted at outpatient clinic reviews at 1, 2, 3 and 6 months after surgery, and followed by telephone or WeChat interviews. The results of the operation were evaluated according to the appearance, texture and sensory recovery of the flap.Results:All 6 flaps survived and the patients completed the postoperative follow-up that lasted for 6-24 (16.7±5.0) months. No necrosis of flap occurred after surgery. The appearance and texture of the flaps were satisfactory without wear and tear. Sensation recover was evaluated by the standered of British Medical Research Council (BMRC), 4 patients recovered to S 3 and 2 patients to S 2. The Mayo score of the elbow joint was good in 2 patient with upper extremity injuries. Of the other 4 patients with lower limb injuries, the knee function evalued by Hospital for Special Surgery(HSS) score were excellent in 3 patients and good in 1 patient, and the American Orthopedic Foot and Ankle Societ(AOFAS) ankle-hind foot function score was excellent in 2 patients and good in 2 patients. There was no infection or function loss at all donor sites. Conclusion:The perforator of an ALTF is relatively constant, and the flap can partially restore sensation. The superior perforator is reliable and the incision area of the flap can be enlarged by anastomosing the superior perforator vessels. It is a better way to reconstruct a large soft tissue defects in limbs.

Objective:To investigate the clinical efficacy and adverse reactions of linezolid in the treatment of gram-positive coccal infections after chemotherapy in older adult patients with leukemia.Methods:Ninety-two older adult patients with leukemia complicated by gram-positive coccal infections, who received treatment in Yiwu Central Hospital from January 2017 to December 2019, were included in this study. They were randomly assigned to receive routine anti-infection treatment (control group, n = 46) or linezolid treatment (observation group, n = 46). Clinical efficacy, the time required for body temperature restoring to normal, and medication time were compared between the two groups. Results:Total response rate was significantly higher in the observation group than in the control group [95.65% (44 /46) vs. 78.26% (36/46), χ2 = 6.13, P = 0.013]. The time required for body temperature restoring to normal and medication time in the observation group were (7.98 ± 1.04) days and (8.58 ± 1.31) days, respectively, which were significantly shorter than those in the control group [(8.85 ± 1.47) days, (9.46 ± 2.52) days, t = 3.27, 2.10, P = 0.001, 0.019). The incidence of adverse reactions was significantly lower in the observation group than in the control group [4.35% (2/46) vs. 19.57% (9/46), χ2 = 5.05, P < 0.05]. Conclusion:Linezolid is highly effective on gram-positive coccal infections after chemotherapy in older adult patients with leukemia. Linezolid treatment requires comparatively shorter time required for body temperature restoring to normal and shorter medication time and is safer than routine anti-infection treatment.

ObjectiveTo investigate the effect of intermittent theta burst stimulation (iTBS) of the multi-target cerebral cortex after stroke on functional recovery of the upper limb of the hemiplegic side. MethodsFrom November, 2019 to August, 2020, 40 stroke patients in Gansu Provine Hospital Rehabilitation Center were included and randomly divided into single-target stimulation group (n = 20) and multiple-target stimulation group (n = 20). Both groups underwent basic neurorehabilitation drug therapy and conventional rehabilitation exercises. The single-target stimulation group received repetitive transcranial magnetic stimulation (rTMS) (iTBS mode) only in the primary motor cortex (M1) of the affected side. The multi-target stimulation group received rTMS (iTBS mode) in the cerebellar cortex of the healthy brain and M1 of the affected side, once a day, six days a week, for four weeks. Before and after treatment, the scores of Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT) and modified Barthel Index (MBI), and the latency and amplitude of somatosensory-evoked potentials N20 were compared. ResultsNo serious adverse reaction occurred during treatment. After treatment, the scores of FMA-UE, MBI and ARAT, and the amplitude and latency of N20 improved in both groups (|t| > 3.478, |Z| > 2.243, P < 0.05); and the scores of FMA-UE and ARAT, and the amplitude of N20 were better in the multiple-target stimulation group than in the single-target stimulation group (t > 2.939, Z = -2.697, P < 0.01). ConclusionMulti-target stimulation is superior to single-target stimulation for improving upper limb motor function and N20 amplitude in the hemiplegics after stroke.

Objective:To investigate the clinical effect of free posterior tibial artery perforator flap in repair of forefoot soft tissue defect.Methods:From January 2017 to January 2021, a retrospective study was conducted on 13 patients with forefoot soft tissue defect, metatarsal head exposed, and forefoot transverse arch integrity, including 9 males and 4 females. The age was (40.0±13.0) years old. Cause of injury: 8 cases of traffic accident injury, 5 cases of heavy object smashing injury. Seven cases had forefoot skin defect and toe damage, and 6 cases had forefoot skin avulsion injury, open toe fracture with tendon, blood vessel and nerve injury. The wound area was 4.5 cm×3.0 cm-8.0 cm×6.0 cm. VSD treatment was performed in the first stage, and free posterior tibial artery perforator flap was used for the second stage. The flap area was 5.5 cm×4.0 cm-9.0 cm×7.0 cm. Outpatient reviews scheduled at 1, 2, 3, and 6 months after surgery, through outpatient clinic, telephone or WeChat. The flaps were evaluated according to appearance, texture, sensory recovery, and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot function scoring system.Results:All 13 flaps survived. The follow-up lasted for 6 to 24 months. The feet were in good shape, walking with weight beries, and the flaps had satisfactory appearance without wear and tear. Five cases were S 3, 6 were S 2, and 2 were S 1. According to AOFAS ankle-hindfoot function score, 4 had excellent scores, 7 were in good, and 2 in fair. Conclusion:The free posterior tibial artery perforator flap has relatively constant perforators, and the pedicle of the middle and upper perforators is longer, and the flap can build part of the sensation. Posterior artery perforator flap is a good flat for repairing the soft tissue defects of the metatarsal head of the forefoot.

Objective:To summarise the clinical experience in replantation of the severed auricle distal to helix with microsurgical technique.Methods:From December 2018 to October 2021, a total of 5 patients with severed auricle injury were treated in the Department of Hand and Foot Surgery of The Affiliated Hospital of Qingdao University. They were 4 males and 1 female with 23-62 years old. After complete debridement of the auricular pinna, the retrograde replantation method was used. For arteries: a dorsal vein of the foot was used to bridge the posterior auricular artery. For veins: 2 patients had the veins directly anastomosed, 2 had the arteriovenous bridging to the posterior ear vein with dorsal foot veins, and the veins in 1 case were not anastomosed. Among the patients, 2 developed venous occlusions after severed auricle, and were treated with bloodletting through small incision at the skin margin. Two patients who received the arteriovenous of the severed auriclse achieved good blood supply. All the patients underwent treatments including anti-freezing, anti-spasm and anti-infection after the emergency surgery. The follow-ups were conducted regularly by telephone and by display photos via WeChat after surgery.Results:All 5 severed auricles were successfully replanted and survived. Postoperative follow-up ranged from 3 months to 2 years, with an average of 10 months. In the 2 cases with venous crisis, the auricles had mild atrophy. All auricles had no obvious pigmentation, and had the sensation recovery back to normal in 1 year after surgery.Conclusion:The pre-judgment of blood vessel quality and high-quality microsurgery skills are the necessary pre-conditions for auricle replantation. For replantation of severed auricle, it is the key to prevent vascular crisis by having the injured blood vessels thoroughly removed.

To report a case of completely amputated ear beyond the anthelix with a severe cross section contusion. After the inspection and exclusion of coronavirus disease (COVID-19) as per prevention and control procedure, an ear replantation surgery was performed under strict protective measures. At 2 week of followed-up, the replanted auricle survived well and the left ear showed a good appearance.

Natural killer (NK) cells are essential in controlling cancer and infection. However, little is known about the dynamics of the transcriptional regulatory machinery during NK cell differen-tiation. In this study, we applied the assay of transposase accessible chromatin with sequencing (ATAC-seq) technique in a home-developed in vitro NK cell differentiation system. Analysis of ATAC-seq data illustrated two distinct transcription factor (TF) clusters that dynamically regulate NK cell differentiation. Moreover, two TFs from the second cluster, FOS-like 2 (FOSL2) and early growth response 2 (EGR2), were identified as novel essential TFs that control NK cell maturation and function. Knocking down either of these two TFs significantly impacted NK cell differentia-tion. Finally, we constructed a genome-wide transcriptional regulatory network that provides a bet-ter understanding of the regulatory dynamics during NK cell differentiation.

Objective To evaluate the use of endoscopic papillary balloon dilation in treatment of choledocholithiasis associated with peripapillary duodenal diverticulum.Methods From January 2017 to July 2018,a retrospective study was conducted on 124 patients with choledocholithiasis associated with peripapillary duodenal diverticula at the Department of Hepatobiliary Surgery,Second Hospital of Hebei Medical University.These patients were divided into the small endoscopic sphincterotomy combined with balloon dilation group (sEST+EPBD,n =60) and the simple papillary balloon dilation group (EPBD n =64).The operation time,one-time success rate of stone removal,complication and hospitalization stay were compared between the two groups of patients.Results The hospitalization expenses of the EPBD group was significantly less than the sEST+EPBD group (P＜0.05).The operation time of the EPBD group was significantly shorten than the sEST+EPBD group (P＜0.05).There were no significant differences in the one-time success rate of stone removal,complication rates and hospitalization stay between the two groups (P＞0.05).Conclusions Compared with sEST+EPBD,treatment of choledocholithiasis in patients with peripapillary duodenal diverticula using simple balloon dilation shortened the operation time,did not increase the complication rates and hospitalization stay.The procedure was safe and effective,and resulted in almost the same one-time success rate of stone removal.