Objective:To evaluate the effects of FLASH irradiation(FLASH-RT) and conventional irradiation (CONV-RT) on radiation-induced injury to the brain tissue of healthy mice using a domestically developed X-FLASH platform.Methods:Ninety healthy 8-week-old male C57BL/6J mice were randomly divided into sham irradiation(Sham) group, CONV-RT group, and FLASH-RT group, with 30 mice in each group. A single dose of 20 Gy whole-brain radiotherapy was administered, with a dose rate of 339 Gy/s for FLASH radiotherapy and 0.067 Gy/s for conventional radiotherapy. The effects of different radiotherapy modalities on neurological function and neuroinflammation were assessed using water maze test, open field test, Nissl staining, and immunohistochemical analysis (GFAP, Iba-1).Results:There were significant differences in body weight between the CONV group and the FLASH group at 8, 9, 10, 11, 12, and 24 d after radiotherapy ( q=2.82-5.31, P<0.05). At 4 months after radiotherapy, there were significant differences between the FLASH group and the CONV group in escape latency, platform crossings, central zone crossings, and Thigmotaxis distance ratio ( q=3.72, 2.92, 3.28, 2.97, P<0.05). Quantitative Nissl staining result revealed significant differences between the CONV group and the FLASH group in the CA3 and DG regions ( q=3.61, 3.21, P<0.05), but not in the CA1 region ( P>0.05). Immunohistochemical result showed a significant difference between the CONV group and the FLASH group in the percentage of GFAP + positive area ( q=2.28, P<0.05), but not in the number of Iba-1 + cells ( P>0.05). Conclusions:Compared to conventional radiotherapy, X-FLASH radiotherapy causes less radiation-induced injury to the brain tissue, thus holding a promising prospect for clinical translation.

Objective:To investigate the clinical characteristics and prognosis of acute pancreatitis (AP) with different etiologies.Methods:The retrospective cohort study was conducted. The clinical data of 702 patients with AP who were admitted to Xuanwu Hospital of Capital Medical University from January 2018 to December 2022 were collected. There were 451 males and 251 females,aged (52±17)years. Observation indicators: (1) clinical characteristics of AP patients with different etiologies; (2) complications and prognosis of AP patients with different etiologies; (3) complications and prognosis of moderately severe and severe AP patients with different etiologies. Comparison of measurement data with normal distribution among multiple groups was conducted using the one-way analysis of variance. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test. Comparison of count data among multiple groups was conducted using the chi-square test. Results:(1) Clinical characteris-tics of AP patients with different etiologies. Of the 702 AP patients, 434 cases were biliary AP, 199 cases were hypertriglyceridemic-induced AP,29 cases were alcoholic AP, and 40 cases were idiopathic AP. There were significant differences in gender,age,body mass index,combined cardiovascular disease,combined diabetes,combined nephrosis,disease severity and modified computed tomography severity index among AP patients with different etiologies ( χ2=24.61, F=48.65, 12.24, χ2=13.67, 12.90, 14.12, 15.56, H=17.62, P<0.05). (2) Complications and prognosis of AP patients with different etiologies. There was no significant difference in infectious pancreatic necrosis,duration of intensive care unit stay,total duration of hospital stay, and death of patients during hospitalization among AP patients with different etiologies ( P>0.05). (3) Complications and prognosis of moderately severe and severe AP patients with different etiologies. Of the 395 patients with moderately severe and severe AP, 217 cases were biliary AP, 128 cases were hypertriglyceridemic-induced AP, 19 cases were alcoholic AP, and 31 cases were idiopathic AP. There were significant differences in renal injury, multiple organ dysfunction syndrome and walled-off necrosis among moderately severe and severe AP patients with different etiologies ( χ2=12.62, 8.25, 14.33, P<0.05), and there was no significant difference in infectious pancreatic necrosis, lung injury, circulation system injury, duration of intensive care unit stay, total duration of hospital stay, or death of patients during hospitalization among moderately severe and severe AP patients with different etiologies ( P>0.05). Conclusions:The clinical charac-teristics vary among AP patients with different etiologies. The risk of complications varies among moderately severe and severe AP patients with different etiologies.

Objective:To evaluate the effects of FLASH irradiation(FLASH-RT) and conventional irradiation (CONV-RT) on radiation-induced injury to the brain tissue of healthy mice using a domestically developed X-FLASH platform.Methods:Ninety healthy 8-week-old male C57BL/6J mice were randomly divided into sham irradiation(Sham) group, CONV-RT group, and FLASH-RT group, with 30 mice in each group. A single dose of 20 Gy whole-brain radiotherapy was administered, with a dose rate of 339 Gy/s for FLASH radiotherapy and 0.067 Gy/s for conventional radiotherapy. The effects of different radiotherapy modalities on neurological function and neuroinflammation were assessed using water maze test, open field test, Nissl staining, and immunohistochemical analysis (GFAP, Iba-1).Results:There were significant differences in body weight between the CONV group and the FLASH group at 8, 9, 10, 11, 12, and 24 d after radiotherapy ( q=2.82-5.31, P<0.05). At 4 months after radiotherapy, there were significant differences between the FLASH group and the CONV group in escape latency, platform crossings, central zone crossings, and Thigmotaxis distance ratio ( q=3.72, 2.92, 3.28, 2.97, P<0.05). Quantitative Nissl staining result revealed significant differences between the CONV group and the FLASH group in the CA3 and DG regions ( q=3.61, 3.21, P<0.05), but not in the CA1 region ( P>0.05). Immunohistochemical result showed a significant difference between the CONV group and the FLASH group in the percentage of GFAP + positive area ( q=2.28, P<0.05), but not in the number of Iba-1 + cells ( P>0.05). Conclusions:Compared to conventional radiotherapy, X-FLASH radiotherapy causes less radiation-induced injury to the brain tissue, thus holding a promising prospect for clinical translation.

Objective:To investigate the clinical characteristics and prognosis of acute pancreatitis (AP) with different etiologies.Methods:The retrospective cohort study was conducted. The clinical data of 702 patients with AP who were admitted to Xuanwu Hospital of Capital Medical University from January 2018 to December 2022 were collected. There were 451 males and 251 females,aged (52±17)years. Observation indicators: (1) clinical characteristics of AP patients with different etiologies; (2) complications and prognosis of AP patients with different etiologies; (3) complications and prognosis of moderately severe and severe AP patients with different etiologies. Comparison of measurement data with normal distribution among multiple groups was conducted using the one-way analysis of variance. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test. Comparison of count data among multiple groups was conducted using the chi-square test. Results:(1) Clinical characteris-tics of AP patients with different etiologies. Of the 702 AP patients, 434 cases were biliary AP, 199 cases were hypertriglyceridemic-induced AP,29 cases were alcoholic AP, and 40 cases were idiopathic AP. There were significant differences in gender,age,body mass index,combined cardiovascular disease,combined diabetes,combined nephrosis,disease severity and modified computed tomography severity index among AP patients with different etiologies ( χ2=24.61, F=48.65, 12.24, χ2=13.67, 12.90, 14.12, 15.56, H=17.62, P<0.05). (2) Complications and prognosis of AP patients with different etiologies. There was no significant difference in infectious pancreatic necrosis,duration of intensive care unit stay,total duration of hospital stay, and death of patients during hospitalization among AP patients with different etiologies ( P>0.05). (3) Complications and prognosis of moderately severe and severe AP patients with different etiologies. Of the 395 patients with moderately severe and severe AP, 217 cases were biliary AP, 128 cases were hypertriglyceridemic-induced AP, 19 cases were alcoholic AP, and 31 cases were idiopathic AP. There were significant differences in renal injury, multiple organ dysfunction syndrome and walled-off necrosis among moderately severe and severe AP patients with different etiologies ( χ2=12.62, 8.25, 14.33, P<0.05), and there was no significant difference in infectious pancreatic necrosis, lung injury, circulation system injury, duration of intensive care unit stay, total duration of hospital stay, or death of patients during hospitalization among moderately severe and severe AP patients with different etiologies ( P>0.05). Conclusions:The clinical charac-teristics vary among AP patients with different etiologies. The risk of complications varies among moderately severe and severe AP patients with different etiologies.

Diabetic ulcer （DU） wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing， and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment， long treatment process， and high morbidity and mortality. Therefore， how to help the rapid healing of DU wounds， reduce the disability rate and mortality rate， protect limb function， and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex， mainly including microcirculation disorder， peripheral neuropathy， inflammation and infection， and excessive apoptosis of cells， involving physiological processes such as wound inflammation， granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Notch， nuclear factor E₂-related factor 2 （Nrf2）， transforming growth factor-β （TGF-β）/Smad， and other signaling pathways， regulate abnormal glucose metabolism， improve microcirculation， inhibit inflammation and oxidative stress， regulate cell proliferation and excessive apoptosis， and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine （TCM） syndrome differentiation and internal and external treatment. Therefore， this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds， aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.

BACKGROUND:In recent years,it has been found that some traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of the skin flap,promote vascular regeneration of the skin flap and prevent skin flap necrosis by activating autophagy. OBJECTIVE:To review the research progress of traditional Chinese medicine monomer regulating autophagy in preventing flap necrosis. METHODS:The Chinese and English key words were"traditional Chinese medicine(TCM),autophagy,skin flaps".The first author searched the relevant articles published in CNKI and PubMed databases from January 2010 to October 2022.A total of 196 articles were retrieved in the preliminary screening and then screened according to the inclusion and exclusion criteria.The quality assessment was conducted by reading the literature titles and abstracts.Finally,55 articles were summarized. RESULTS AND CONCLUSION:(1)The regulation of autophagy is mediated by AMPK/mTOR,PI3K/AKT and other signaling pathways.Activation of autophagy can alleviate the oxidative stress and apoptosis of the flap,promote the regeneration of blood vessels in the flap,and prevent flap necrosis.(2)Terpenoids(Betulinic acid,Andrographolide,Notoginseng Triterpenes,Catalpa),phenolic compounds(Resveratrol,Curcumin,Gastrodin),phenolic acids(Salvianolic acid B)and steroid compounds(Pseudoginsenoside F11)in traditional Chinese medicine monomers can alleviate oxidative stress and apoptosis of skin flap by regulating related signaling pathways to activate autophagy,promote skin flap angiogenesis and promote skin flap survival.(3)Studying the research progress of traditional Chinese medicine monomer to prevent flap necrosis by regulating autophagy can provide a reference and theoretical basis for traditional Chinese medicine to prevent flap necrosis and promote flap healing in the clinic.

To implement the strategy of healthy China and promote the construction of "new medicine science", it is urgent to focus on new needs and challenges to advance the reform of medical education curricula in China. Using literature research methods, we summarize the process of modern medical education curriculum reforms in the United States, and discuss the main features of the third-round reforms—introducing the concept of value-based medicine, offering health systems science courses, and promoting the curriculum system reform from the perspectives of learning time, curriculum integration, and learning methods. Based on these features, we put forward the enlightenment for the reform of medical education curricula in China.

Objective To explore the effect of femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE) femtosecond laser in the treatment of myopic astigmatism with thin cornea. Methods From September 2022 to September 2023, 128 patients with thin cornea myopic astigmatism in the hospital were selected and randomly divided into FS-LASIK group (64 cases, 128 eyes, receiving FS-LASIK) and SMILE group (64 cases, 124 eyes, receiving SMILE). The visual acuity [uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA)] before surgery and at 1 year after surgery, refractive parameter spherical equivalent (SE) at 3, 6 and 12 months after surgery, corneal surface morphology [average corneal curvature (K_Ave), surface regularity index (SRI), surface asymmetry index (SAI)] before surgery and at 1 year after surgery, corneal biomechanic indicators[corneal expansion comprehensive deviation analysis index (BAD-D), corneal biomechanical index (CBI), total biomechanical index (TBI)] and corneal injury degree [corneal endothelial cell count, corneal endothelial cell size, coefficient of variation (CV)] and differences in postoperative astigmatism correction vector indicators [magnitude of error (ME), angle of error (AE), correction index (CI), and index of success (IOS)] were compared. Residual stromal bed thickness and the incidence of complications after surgery were recorded. Results One year after surgery, both UCVA and BCVA in both groups were improved compared with preoperation (P < 0.05), but there were no significant between-group differences (P>0.05). At 3, 6, and 12 months postoperatively, the SE levels in both groups were higher than preoperation (P < 0.05); however, there were no statistically significant differences in SE levels between the groups at above time points (P>0.05). One year after surgery, K_Ave, SRI, and SAI in both groups were lower than preoperative levels, and the SMILE group was lower than those in the FS-LASIK group (P < 0.05). One year after operation, BAD-D and TBI in both groups were higher than preoperative levels, while CBI was lower than preoperative levels; however, BAD-D and TBI in the SMILE group were lower than those in the FS-LASIK group, and CBI was higher than that in the FS-LASIK group (P < 0.05). One year after surgery, corneal endothelial cell counts in both groups were lower than preoperative levels, and CV of corneal endothelial cell size was higher than preoperative levels; however, corneal endothelial cell count in the SMILE group were higher than those in the FS-LASIK group, and the CV of corneal endothelial cell size was lower than that in the FS-LASIK group (P < 0.05). There were no statistically significant differences in ME, AE, CI, and IOS between the two groups (P>0.05). The residual stromal bed thickness was (302.01±55.03) μm in the FS-LASIK group and (310.23±46.03) μm in the SMILE group after surgery, with no statistically significant between-group difference (t=1.284, P=0.200). One year after surgery, there were 5 cases of dry eye in the FS-LASIK group and 2 cases in the SMILE group, with no statistically significant difference in incidence of dry eye between the two groups (χ²=1.227, P=0.268). Conclusion For patients with myopic astigmatism with thin cornea, both FS-LASIK and SMILE can achieve satisfactory improvement in visual acuity and refractive state, and the latter one has a relatively small impact on the integrity of corneal structure, biomechanical stability and surgical injury.

【Objective】 To observe the effect of Xiaozhongzhitong Mixture on ischemia-reperfusion injury of rat skin flaps and p38MAPK-PPARγ/NF-κB signaling pathway. 【Methods】 After flap operation, the survival of rat back flaps and flap survival rate were observed. HE staining, TUNEL staining, and qRT-PCR were used to detect the degree of nuclear destruction, as well as the distribution characteristics and mRNA expression levels of p38MAPK, PPARγ, and Nf-κB in vascular endothelial cells of rat flaps, respectively. 【Results】 The flap survival area in sham operation group was the largest, and it was the smallest in model control group and PPARγ inhibitor group. HE staining and TUNEL staining results showed that the flap tissue cells of rats in model control group and PPARγ inhibitor group were severely damaged and obvious apoptotic cells were seen. In model group, rats’ skin flap tissue cells were arranged in a single layer, and the nucleus was intact and clear. qRT-PCR experiment results showed that compared with model group, the expressions of p38MAPK and Nf-κb in the flap tissue of rats in Xiaozhong Zhicong Mixture group were inhibited (P<0.05), while the expression of PPARγ was increased (P<0.05). When the blocker was added, the expressions of p38MAPK, NF-κB and PPARγ in the flap tissue were further suppressed. 【Conclusion】 Xiaozhongzhitong Mixture can alleviate the infiltration of inflammatory cells in the rat model of skin flap ischemia-reperfusion injury, reduce inflammation and the production of apoptotic cells, thereby alleviating the ischemia-reperfusion injury of skin flaps and promoting the survival of the flaps. The mechanism may be related to the inhibition of p38MAPK-PPARγ/NF-κB signaling pathway.

Objective:To compare the safety of the generic and the original regorafenib tablets.Methods:Two single center, randomized, open-label, 2-period self-crossover phase I clinical trials (single dose) were conducted under fasting condition and with low-fat meal respectively in healthy adult volunteers. The test preparation (T) of regorafenib was produced by Beijing Sl Pharmaceutical Co.,Ltd. and the reference preparation (R) was produced by Bayer HealthCare Pharmaceuticals Inc. In the 2 trials, male healthy subjects were randomly divided into 2 groups, respectively, and took 2 times of the preparations with different order in each group, which were R-T group (subjects took R on day 1 and then T on day 13) and T-R group (subjects took T on day 1 and then R on day 13). The subjects took drugs under fasting condition and with low-fat meal in the 2 trials respectively. After medication, vital signs detection, electrocardiogram, general physical examination, blood routine, blood biochemical, coagulation function, and other tests were performed regularly, and the occurrence of adverse events (AEs) were recorded and the severity of AEs was assessed.Results:Sixty-four subjects were enrolled in the trial under fasting condition, including 32 in the T-R group and 32 in the R-T group, and the safety data was obtained from 61 and 57 subjects taking T and R, respectively. Seventy-six subjects were included in the postprandial trial, including 38 in the T-R group and 38 in the R-T group, and the safety data was obtained from 74 subjects taking T and R, respectively. In the 2 trials, there was no significant difference in the incidence of AEs between subjects taking T and those taking R [41.0% (25/61) vs. 31.6% (18/57), χ2=1.125, P=0.289; 56.8% (42/74) vs. 45.9% (34/74), χ2=0.183, P=0.188]. A total of 230 AEs occurred in the 2 trials, of which 228 cases were grade 1 (99.1%, 131 and 97 AEs occurred in subjects taking T and R, respectively), 2 cases were grade 2 (0.9%, 1 AE occurred in subjects taking T and R, respectively), and no grade ≥ 3 AEs occurred. The types of AEs occurred in the 2 trials were the same, of which bradycardia was the most common, followed by prolonged QT interval of ECG. All ECG abnormalities were found during routine examinations, and no subjects had obvious clinical symptoms. Conclusion:The safety of the generic and the original regorafenib tablets was consistent after a single dose administration under fasting condition and with low-fat meal.