AIM: To observe the early retinal degeneration and activation of microglia in C57BL/6N(Crb1rd8/rd8)mice.METHODS:Totally 15 male SPF C57BL/6N mice and 15 male SPF C57BL/6J mice were raised normally, and fundus photography examinations were performed by Micron-Ⅲ at the time of 0, 4, 8, 12 wk of enrollment to calculate the number and area of retinopathy. At the end of experiment, all mice were sacrificed and the right eyeballs were removed to prepare retinal tissue slices. After HE staining, the retinal tissue morphology was observed under optical microscope while the location and level of CX3CR1 expression were detected in immunohistochemical staining. The left eyeballs were removed to isolate retina, then Western-Blot was used to analyze the expression of CD86 and CD206 proteins in retina, and the concentration of IL-1β, IL-6, TNF-α, IL-4 and IL-10 in retina was detected by electrochemiluminescence.RESULTS:The result of fundus photography examinations showed that the number of retinopathy in the C57BL/6N significantly increased at 4, 8, and 12 wk, and there were differences in variations compared with the C57BL/6J at the same time point(all P<0.05). In the changes in area of retinopathy, there was a difference between two groups at 12 wk(P<0.05), but no difference in variations within groups(both P>0.05). HE staining of retinal tissue showed that the retinal structure of C57BL/6N mice was abnormal, with loose and disordered cell arrangement, and the photoreceptor layer was obviously protruding to the inner side of retina with a drusen-like protrusion. The retinal structure of C57BL/6J mice was clearer, with orderly cell arrangement and no obvious abnormality. Immunohistochemical results showed that CX3CR1 was highly expressed in ganglion cell layer, inner and outer plexiform layer, photoreceptor cell layer and lesion in the retina of C57BL/6N mice, with a mean density of 0.285±0.056 in C57BL/6N and 0.189±0.084 in C57BL/6J mice(P<0.05). The results of Western-Blot showed that the expression of CD86 and CD206 in retina of C57BL/6N increased compared with that in C57BL/6J to varying degrees, and the difference of CD86 was statistically significant(P<0.05). The results of cytokine detection showed that the level of IL-1β, TNF-α in C57BL/6N was significantly higher than that of C57BL/6J, while IL-10 was significantly lower(all P<0.05).CONCLUSION: The retinal degeneration of C57BL/6N(Crb1rd8/rd8)mice progressed slowly and gradually aggravated with age. The retinal structure of the lesion was disordered and accompanied by microglial infiltration dominated by M1 polarization.

Objective To propose a classification method for ultrasound images of pedicle screw canals based on radiomics analysis,and to evaluate the integrity of the screw canal.Methods With thoracolumbar spine specimens from 4 fresh cadavers,50 pedicle screw canals were pre-established and ultrasound images of the canals were acquired.A total of 2 000 images(1 000 intact and 1 000 damaged canal samples)were selected.The dataset was randomly divided in a 4∶1 ratio using 5-fold cross-validation to form training and testing sets(consisting of 1 600 and 400 samples,respectively).Firstly,the optimal radius of the region of interest was identified using the Otsu's thresholding method,followed by feature extraction using pyradiomics.Principal component analysis and the least absolute shrinkage and selection operator algorithm were employed for dimensionality reduction and feature selection,respectively.Subsequently,3 machine learning models(support vector machine[SVM],logistic regression,and random forest)and 3 deep learning models(visual geometry group[VGG],ResNet,and Transformer)were used to classify the ultrasound images.The performance of each model was evaluated using accuracy.Results With a region of interest radius of 230 pixels,the SVM model achieved the highest classification accuracy of 96.25%.The accuracy of the VGG model was only 51.29%,while the accuracies of the logistic regression,random forest,ResNet,and Transformer models were 85.50%,80.75%,80.17%,and 75.18%,respectively.Conclusion For ultrasound images of pedicle screw canals,the machine learning model performs better than the deep learning model as a whole,and the SVM model has the best classification performance,which can be used to assist physicians in diagnosis.

Medical Physics is an interdiscipline which is formed by applying the basic principles, methods, and techniques of physics to clinical medical research such as prevention, diagnosis, and treatment of human diseases, and it is a compulsory professional basic course for medical students. However, there are many medical students reflect that the content of this course is obscure and difficult to understand. Teaching effect is not ideal. The main reasons are that the teaching method is single and the reference materials are few. Based on the actual situation of the course, Hebei Medical University, China promotes formative evaluation from the content of teaching materials, teaching means, and other aspects. At the same time, by combining with the Internet, the digital construction has been realized, deepening the reform of the Medical Physics curriculum, and remarkable results have been achieved.

At present, surgical resection remains as the main treatment for patients with colorectal cancer (CRC). Alongside the progress in oncologic surgical technique, minimally invasive approaches, such as laparoscopy and transanal total mesorectal excision (taTME), and individualized surgical options, such as lateral lymph node dissection and multivisceral resection, the patient mortality associated with traditional surgical approaches has been improved. Neoadjuvant therapy can decrease local recurrence and distant metastasis, and improve the survival of patients. The optimization of adjuvant therapy shortens treatment cycle, reduces treatment risk and toxicities. Recently, neoadjuvant immunotherapy has become the new standard of the treatment for mismatch repair-deficient or microsatellite instability high CRC. However, it shows unsatisfactory outcomes in patients with mismatch repair-proficient/microsatellite stable CRC, which needs overcoming the limi-tation of CRC genephenotype. With more researches on CRC, the more biomarkers predicting the response to treatment will be found and the novel comprehensive treatment of CRC will be developed, which will make the treatment of CRC more individualized and accurate, and finally benefit more patients.

Lateral lymph node metastasis (LLNM) is one of the major causes for post-operative local recurrence of middle and low rectal cancer. At present, there are still controversies on the diagnosis and treatment of LLNM. The radiological assessment of LLNM generally relies on morphological criteria such as the size or shape of the node or the response to therapy, in which the diagnostic accuracy of MRI is superior to that of other imaging techniques. Neoadjuvant chemoradiotherapy could not achieve good local control for suspicious LLNM. Lateral lymph node dissection (LLND) can reduce tumor local recurrence significantly, but the clinical value of LLND in survival and quality of life of patients has been questioned. 4K laparoscope can decrease the incidence of perioperative complications and urinary and sexual dysfunction to a certain extent. Thus, selective LLND should be undertaken to patients with suspicious LLNM after neoadjuvant chemoradiotherapy, in order to reduce tumor local recurrence and improve the prognosis of patients. The authors elaborate on diagnosis and treatment including surgery or chemoradiotherapy of LLNM in 4K laparoscopic surgery for middle and low rectal cancer combined with their own experiences.

Lateral lymph node metastasis (LLNM) is the main metastatic mode and the major cause of locoregional recurrence of mid-low rectal cancer. Single chemoradiotherapy cannot achieve good local control for LLNM, while the argument against performing lateral lymph node dissection (LLND) is the increased rate of urinary and sexual dysfunction after surgery. Ultra-high definition surgical field and delicate resolution by 4K laparoscopic surgical system will be helpful to achieve good tumor clearance and function preservation by identification and exposure of the important anatomic structures such as pelvic autonomic nerve and internal iliac vessels. Therefore, selective LLND can reduce local recurrence rates, particularly in the pelvic sidewall. LLND with autonomic nerve preservation by 4K laparoscopic system is expected to further decrease the risk of perioperative complications and urinary and sexual dysfunction in appropriate patients with neoadjuvant chemoradiotherapy.

Liquid preparations are the commonly used oral dosage forms in pediatric clinical practice.This review introduces the pediatric oral liquid dosage forms including extemporaneous preparation of oral liquid formulations, oral liquid sustained and controlled release formulations, nanosuspensions, nanoemulsions, self-nanoemulsions and milk-based liquid formulations.In addition, the efficient flavoring and taste masking technologies, using safe pharmaceutical excipients, high-demanding technical standards and verification strategies, establishing excellent workflow management systems can contribute to the development and application of pediatric oral liquid dosage forms which are safer, more effective and better compliant.This review is helpful in laying the relevant theoretical foundation for further studies on pediatric oral liquid dosage forms.

Objective:Through constructing an online question database of medical physics, teachers and students can make use of the Internet to realize interaction in or after class, so students' ability of independent learning and the quality of teaching can be improved.Methods:Based on teaching outlines, the type, quantity and difficulty of the test questions were discussed and determined by teachers in the teaching and research office, and the online question database of medical physics was constructed with the help of Internet platform to realize self-testing and teacher-student interaction.Results:Through the construction and application of online question database, students' learning initiative was mobilized, the effectiveness of teacher-student interaction was improved, and empirical materials for teaching formation evaluation were obtained. Self-examination and teacher-student interaction help improve students independent learning and problem solving ability. And data generated on the platform enable teachers to know students' learning situation and their teaching quality.Conclusion:The construction and application of Internet + digital online question database of medical physics can greatly promote the teaching effect.

Objective: To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) with high risk factors. Methods: Data of 101 patients who were diagnosed with stage II-III rectal cancer with high risk factors and received TNT between March 2015 and January 2018 at West China Hospital of Sichuan University were analyzed retrospectively. Inclusion criteria: (1) patients were diagnosed with stage II-III rectal cancer by high-resolution MRI combined with CT and endorectal ultrasound; (2) at least one high risk factor: cT4a, cT4b, cN2, EMVI+, CRM+ and lateral lymph node+; (3) distance from tumor to anal verge was within 15 cm; (4) Eastern Collaborative Oncology Group (ECOG) performance status score was 0-1; bone marrow function, liver function and kidney function were suitable for chemoradiotherapy; (5) patients were treated with TNT strategy; (6) the follow-up data and postoperative pathological data were complete. Patients with previous rectal cancer surgery (except prophylactic colostomy), pelvic radiotherapy, and systemic chemotherapy, those with distant metastases, those without neoadjuvant radiotherapy, those receiving less than 4 cycles of neoadjuvant chemotherapy were excluded. The regimen of TNT: 3 cycles of induction CAPOX (oxaliplatin plus capecitabine) were followed by pelvic radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after radiotherapy. Total mesorectal resection (TME) or watch-and-wait strategy was selected according to the therapeutic effect and patients' wishes. Short-term efficacy, including tumor regression grade (TRG), pathological complete response (pCR), clinical complete response (cCR), postoperative complications within 30 days of surgery, and adverse events (AE) to radiotherapy and chemotherapy (measured using CTCAE 4.0) was analyzed. Results: The 101 patients included 68 males (67.3%) and 33 females (32.7%) with a median age of 54 years. The proportion of patients with cT4a, cT4b, cN2 and enlarged lateral lymph node was 13.9%, 29.7%, 56.4% and 43.6%, respectively. The mean cycle of neoadjuvant chemotherapy was 6.0±1.3. Seventy-five patients (74.3%) received at least 6 cycles of neoadjuvant chemotherapy and 100 (99.0%) completed radiotherapy. The mean cycle of induction and consolidation chemotherapy was 2.0±0.9 and 2.8±1.0 respectively. Most common grade 3 AE was leucopenia (n=13, 12.9%) and thrombocytopenia (n=7, 6.9%). Grade 3 diarrhea and radiation dermatitis were observed in 5 cases (5.0%) respectively. Grade 3 anemia and rectal pain were observed in 4 cases (4.0%) respectively. And rectal mucositis was observed in 2 cases (2.0%). Most of the AE was observed during concurrent chemoradiotherapy. No grade 4 or higher AE was observed. After TNT, 32 patients (31.7%) achieved pCR or cCR, and 62 patients (60.4%) achieved partial response (PR). Only 2 patients (2.0%) developed distant metastasis after chemoradiotherapy, while the other patients did not show disease progression. Seven patients (6.9%) with cCR refused surgery and selected watch-and-wait, while 7 patients without cCR still refused surgery. The other 87 patients (86.1%) underwent TME successfully. The mean interval from the completion of chemoradiotherapy to surgery was (20.1±8.5) weeks. The R0 resection rate was 97.7% (85/87).The morbidity of surgical complication was 16.1% (14/87), including pelvic infection or abscess in 6 cases (6.9%), anastomotic leakage in 3 (3.4%), hemorrhage in 2 (2.3%), and gastrointestinal dysfunction in 3 (3.4%). Pathological findings revealed that 24 cases (27.6%) had TRG 0, 20 (23.0%) had TRG 1, 30 (34.5%) TRG 2, and 13 (14.9%) TRG 3. Conclusion TNT is safe and has good short-term efficacy for locally advanced rectal cancer patients with high risk factors.

Objective To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) with high risk factors. Methods Data of 101 patients who were diagnosed with stage II?III rectal cancer with high risk factors and received TNT between March 2015 and January 2018 at West China Hospital of Sichuan University were analyzed retrospectively. Inclusion criteria: (1) patients were diagnosed with stage II?III rectal cancer by high?resolution MRI combined with CT and endorectal ultrasound; (2) at least one high risk factor: cT4a, cT4b, cN2, EMVI+, CRM+and lateral lymph node+; (3) distance from tumor to anal verge was within 15 cm;(4) Eastern Collaborative Oncology Group (ECOG) performance status score was 0?1; bone marrow function, liver function and kidney function were suitable for chemoradiotherapy; (5) patients were treated with TNT strategy; (6) the follow?up data and postoperative pathological data were complete. Patients with previous rectal cancer surgery (except prophylactic colostomy), pelvic radiotherapy, and systemic chemotherapy, those with distant metastases, those without neoadjuvant radiotherapy, those receiving less than 4 cycles of neoadjuvant chemotherapy were excluded. The regimen of TNT: 3 cycles of induction CAPOX (oxaliplatin plus capecitabine) were followed by pelvic radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after radiotherapy. Total mesorectal resection (TME) or watch?and?wait strategy was selected according to the therapeutic effect and patients' wishes. Short?term efficacy, including tumor regression grade (TRG), pathological complete response (pCR), clinical complete response (cCR), postoperative complications within 30 days of surgery, and adverse events (AE) to radiotherapy and chemotherapy (measured using CTCAE 4.0) was analyzed. Results The 101 patients included 68 males (67.3%) and 33 females (32.7%) with a median age of 54 years. The proportion of patients with cT4a, cT4b, cN2 and enlarged lateral lymph node was 13.9%, 29.7%, 56.4% and 43.6%, respectively. The mean cycle of neoadjuvant chemotherapy was 6.0 ± 1.3. Seventy?five patients (74.3%) received at least 6 cycles of neoadjuvant chemotherapy and 100 (99.0%) completed radiotherapy. The mean cycle of induction and consolidation chemotherapy was 2.0 ± 0.9 and 2.8 ± 1.0 respectively. Most common grade 3 AE was leucopenia (n=13, 12.9%) and thrombocytopenia (n=7, 6.9%). Grade 3 diarrhea and radiation dermatitis were observed in 5 cases (5.0%) respectively. Grade 3 anemia and rectal pain were observed in 4 cases (4.0%) respectively. And rectal mucositis was observed in 2 cases (2.0%). Most of the AE was observed during concurrent chemoradiotherapy. No grade 4 or higher AE was observed. After TNT, 32 patients (31.7%) achieved pCR or cCR, and 62 patients (60.4%) achieved partial response (PR). Only 2 patients (2.0%) developed distant metastasis after chemoradiotherapy, while the other patients did not show disease progression. Seven patients (6.9%) with cCR refused surgery and selected watch?and?wait, while 7 patients without cCR still refused surgery. The other 87 patients (86.1%) underwent TME successfully. The mean interval from the completion of chemoradiotherapy to surgery was (20.1±8.5) weeks. The R0 resection rate was 97.7% (85/87).The morbidity of surgical complication was 16.1% (14/87), including pelvic infection or abscess in 6 cases (6.9%), anastomotic leakage in 3 (3.4%), hemorrhage in 2 (2.3%), and gastrointestinal dysfunction in 3 (3.4%). Pathological findings revealed that 24 cases (27.6%) had TRG 0, 20 (23.0%) had TRG 1, 30 (34.5%) TRG 2, and 13 (14.9%) TRG 3. Conclusion TNT is safe and has good short?term efficacy for locally advanced rectal cancer patients with high risk factors.