AIM: To compare the visual quality in patients with low-to-moderate myopia after 0.05 D interval spherical lens optometry-guided small-incision lenticule extraction(SMILE)and conventional 0.25 D interval spherical lens optometry-guided SMILE.METHODS: Retrospective study. A total of 400 cases(400 eyes)with low-to-moderate myopia that underwent SMILE in the ophthalmology department of 989th Hospital of Joint Logistic Support Force from August 2021 to August 2023 were enrolled and the data from the right eyes were collected for analysis. According to the method of optometry test modality, they were divided into 0.05 D group and 0.25 D group, with 200 eyes in each group. The differences were compared between the two groups of patients in intraoperative corneal ablation thickness, uncorrected distance visual acuity(UDVA), high-order corneal aberrations(HOA), spherical aberrations, vertical coma, horizontal coma and trefoil aberrations before and at 1, 3 and 6 mo after surgery. Additionally, the percentage of eyes with residual spherical equivalent(SE)≤±0.25 D, postoperative visual symptoms and scores on the quality of visual(Qov)were compared between the two groups at 6 mo after surgery.RESULTS: The corneal ablation thickness in the 0.05 D group was 92.78±16.56 μm, which was slightly higher than that in the 0.25 D group(83.24±17.33 μm; P<0.001). The UDVA at each postoperative time point in the 0.05 D group was superior to that in the 0.25 D group(all P<0.001). The HOA, spherical aberration, horizontal coma and vertical coma in the two groups at 1, 3 and 6 mo after operation were higher than those before operation(all P<0.05). The spherical aberration in the 0.05 D group at each time point after surgery were higher than those in the 0.25 D group, and vertical coma were lower than those in the 0.25 D group(all P<0.05). At 6 mo postoperatively, the percentage of eyes with residual SE ≤±0.25 D in the 0.05 D group was 97.5%(195 eyes), which was higher than 87.5%(175 eyes)in the 0.25 D group(P<0.05). The most common adverse visual symptoms after SMILE in both groups were hazy vision and glare. The total Qov score in the 0.05 D group was 0.35(0.24, 0.55), which was lower than [0.62(0.32, 0.89)] in the 0.25 D group(P<0.05).CONCLUSION: Compared with conventional 0.25 D interval spherical lens optometry-guided SMILE, the 0.05 D interval spherical lens optometry-guided SMILE for the correction of low-to-moderate myopia has better predictability and can achieve better vision and visual quality.

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

AIM: To investigate the early visual quality after 0.05 D interval spherical lens optometry-guided small incision lenticule extraction(SMILE)for the correction of different degrees of myopia.METHODS: Retrospective study. A total of 200 cases(200 eyes)that underwent SMILE at the 989th Hospital of Joint Logistic Support Force from May to September 2023 were selected. The 0.05 D optometry was used to measure diopter. According to the preoperative spherical equivalent(SE), they were divided into low-to-moderate myopic group(>-6.0 D)and high myopic group(≤-6.0 D), with 100 eyes in each group. The total high-order corneal aberration(HOA), spherical aberration, coma and trefoil aberration were compared between the two groups preoperatively and at 6 mo postoperatively, and the quality of vision questionnaire was completed.RESULTS: The HOA, spherical aberration and vertical coma aberration in the two groups at 6 mo after operation were significantly higher than those before operation(all P<0.05). At 6 mo postoperatively, the HOA, spherical aberration and vertical coma aberration in the low-to-moderate myopic group were lower than those in the high myopic group(all P<0.05). The scores of the quality of vision questionnaire, near vision, night vision, night glare and visual fatigue in the low-to-moderate myopic group were all higher than those in the high myopic group(all P<0.05).CONCLUSION: Both low-to-moderate myopia and high myopia after the 0.05 D interval spherical lens optometry-guided SMILE had some visual symptoms, but great visual quality can be obtained after surgery.

Objective To discover 5-HT2A receptor antagonist molecules with novel structures and explore their structure-activity relationship through structure-and mechanism-based drug design,synthesis and activity evaluation.Methods The way in which pimovanserin interacted with 5-HT2A receptor was analyzed via molecular docking,molecular dynamics simulation and binding free energy calculations.Based on the results of this study,the 5-HT2A receptor antagonist target compounds with novel structures were designed using pimovanserin as the lead molecule.According to the structures of target compounds,corresponding synthetic routes were designed.The heterocyclic methylamine intermediates were obtained by reductive amination or reduction reaction from heterocyclic formaldehyde or heterocyclic methanonitrile before being reacted with 4-(4-fluorobenzylamino)-1-methylpiperidine to obtain the target compounds using CDI urea synthesis method.The inhibitory activity of the target compounds against 5-HT2A receptor was tested at the cellular level,and the anti-hallucinogenic effects of the target compounds were tested in the mouse head twitch response model.Results Twelvenovel compounds were synthesized and their structures were confirmed by HR-MS,1H-NMR and 13C-NMR.The results of the activity assay showed that compounds 6a,6c and 6d exhibited better 5-HT2Areceptor inhibitoryactivity with IC50 values of 120,152 and 285 nmol/L,respectively while compounds 6c and 6d exhibited better anti-hallucinogenic activity in mice with inhibition rates of 97.0％and 82.9％(10 mg/kg),respectively.Conclusion The novel compound 6c and 6d have shown strong 5-HT2A receptor inhibitoryactivity and anti-hallucinogenic activity and deserve more research.Structure-activity relationship analyses of target compounds indicate that the repulsion of the heterocyclic ring with basic N atoms and the accommodation of the heterocyclic ring without basic N atoms by the side extended pocket of the 5-HT2A receptor could significantly affect the ex vivo and in vivo effects of antagonists.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Liver cirrhosis-related cardiomyopathy (CCM) is a common and easily overlooked complication associated with liver cirrhosis. Because of the high incidence and impact on success of the liver transplantation and the transcarotid intrahepatic portosystemic shunt surgery, it has attracted the attention of researchers in the field recently. Liver cirrhosis patients have liver morphological alterations, which result in increased serum level of total bile acids and changes in bile acid composition. The increased bile acid concentrations are cardiotoxic and change cardiac functions. This study discussed and summarized recent advancements in the role of bile acids in cirrhosis-related cardiomyopathy in three aspects, i.e., changes in bile acid metabolism in liver cirrhosis patients, effects of bile acid on changes in cardiac functions, and ursodeoxycholic acid as a potential therapeutic agent for CCM. This review expects to provide novel approaches for future prevention and treatment of CCM.

Objective:To explore the feasibility and clinical efficacy of oblique lateral interbody fusion (OLIF) in the treatment of adjacent segment disease (ASDis).Methods:Retrospective analysis was conducted on the data of 31 patients with ASDis treated by OLIF in four medical centers from June 2015 to December 2018. There were 17 males and 14 females. The average age was (65.7±3.4) years (range, 59 to 75 years). 19 cases received single-segment fixed fusion, 11 cases received double-segment fixed fusion and 1 case received three-segment fixed fusion. Original fixed fusion site: 1 case of L 1, 2, 3 cases of L 3, 4, 11 cases of L 4, 5, 4 cases of L 5S 1, 6 cases of L 3-L 5, 5 cases of L 4-S 1, and 1 case of L 3-S 1. The time from the initial fixation and fusion to this admission was 82.5±45.5 months (rang, 24 to 180 months). ASDis occurred at the proximal end of the fixed fusion segment in 28 cases and at the distal end in 3 cases. The types of ASDis: degenerative disc disease in 11 cases, lumbar spinal stenosis in 15 cases, degenerative spondylolisthesis in 2 cases, and degenerative scoliosis in 3 cases. The location of ASDis: 6 cases of L 2, 3, 12 cases of L 3, 4, 6 cases of L 4, 5, 3 cases of L 1-L 3, 1 case of L 2-L 4, and 3 cases of L 1-L 4. At admission, 3 cases of lumbar internal fixation had been removed and 28 cases of internal fixation remained. Stand-alone OLIF was performed in 19 cases, OLIF combined with pedicle screw fixation in 8 cases, and OLIF combined with cortical screw fixation in 4 cases. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate the low back pain and lumbar function before operation and at the last follow-up, and the imaging results and complications were observed. Results:All patients were followed up. The follow-up time was 23.6±9.6 months (range, 12 to 60 months). The operation time was 73.8±25.3 mins (range, 40 to 180 min), and the intraoperative blood loss was 86.2±67.4 ml (range, 20 to 310 ml). The average blood loss in each segment was 24.8 ml. During the operation, there were 1 case of segmental vein injury, 7 cases of endplate injury, 2 cases of transient iliopsoas muscle weakness, 1 case of thigh pain and numbness, and 1 case of incomplete intestinal obstruction. There was no incision necrosis and infection. The VAS score of low back pain decreased from 5.9±1.9 before operation to 1.4±0.6 at the last follow-up, with a statistically significant difference ( t=8.47, P<0.001). The ODI index recovered from 45.2%±5.7% before operation to 13.8%±4.7% at the last follow-up, with a statistically significant difference ( t=7.92, P<0.001). The height of intervertebral space increased from 8.7±1.6 mm before operation to 11.4±1.9 mm after operation and 9.9±1.8 mm at the last follow-up. There was a statistically significant difference between postoperative and preoperative height of intervertebral space ( F=4.15, P=0.007). There was a statistically significant difference between the last follow-up and postoperative height of intervertebral space ( P=0.011). During the follow-up, there were 13 cases of fusion cage subsidence, 1 case of fusion cage displacement, and no case of internal fixation loosening or fracture. The intervertebral fusion rate was 94%(29/31) and the complication rate was 42%(13/31). Conclusion:ASDis is a common complication after lumbar fixation and fusion, and requires surgical treatment. OLIF is a reliable method to treat ASDis as it has advantages of small trauma, high fusion rate and low complication rate.

Objective:To evaluate the clinical efficacy of staged surgery in treatment of calf Gustilo-Anderson type IIIC fracture.Methods:A retrospective case series was conducted to analyze clinical data of 16 patients with calf Gustilo-Anderson type IIIC fracture admitted to Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2017 to December 2019. There were 12 males and 4 females, with the age of (38.6±8.2)years (range, 18-53 years). All patients had limb salvage treatment at one stage in the emergency department. The survival of the limb and the occurrence of vascular crisis were examined within one week after limb salvage. The second stage involved the repair of skin and soft tissue defects with the defect area from 12.0 cm×5.0 cm to 20.0 cm×8.0 cm using free flaps. The survival of the flap, vascular crisis, and donor site healing within two weeks after the flap procedure. The third stage used bone graft revision and bone lengthening technology to repair bone tissue. The lower extremity functional scale (LEFS) and Mazur ankle joint function score were used to evaluate the function of the affected limb before bone repair and at the last follow-up. The fracture healing and related complications were observed at the last follow-up.Results:All patients were followed up for (14.2±4.6)months (range, 8-20 months). At one stage, the limb-saving surgery was successful in all patients, among which one had vascular crisis. At second stage, free flaps survived in all patients, among which two had vascular crisis. All donor areas were healed by first intention. At third stage, the LEFS of the affected limb was increased from (32.0±7.4)points before bone repair to (48.0±10.2)points at the last follow-up ( P<0.01) and the Mazur score was increased from (50.9±15.3)points before bone repair to (73.8±11.9)points at the last follow-up ( P<0.01). All bone defects were repaired and healed without complications such as infection or osteomyelitis at the last follow-up. Conclusion:For calf Gustilo-Anderson type IIIC fracture, the staged strategy can effectively save limbs and restore limb function.

Objective:To compare the clinical outcomes and complications of oblique lateral interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach and posterior interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach by channel for lumbar spinal stenosis.Methods:A retrospective study was conducted on 73 patients who underwent surgical treatment for lumbar spinal stenosis from Jun 2015 to Jun 2017, including 33 males and 40 females. The average age was 66.8±7.94 years (from 39-85 years). These diseases occured at L 3/4 in 5 patients and L 4/5 in 68 patients. Random according to the time of admission, 38 cases were treated with oblique lateral interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach (oblique lateral fusion group), and 35 cases with posterior interbody fusion combined with bilateral pedicle screw fixation through intermuscular approach by channel (posterior fusion group). The clinical results, image data and complications were compared between the two groups. Results:All patients in both groups had operation performed smoothly. The operation time was 99±8.96 min in the oblique lateral fusion group and 96.8±9.57 min in the posterior fusion group, and there was no significant difference between the two groups. The intraoperative bleeding in the oblique lateral fusion group 80±24.72 ml was significantly less than that in the posterior fusion group 261±52.87 ml ( t=9.621, P<0.05). No incision infection occurred after surgery. The VAS score of lumbar incision 72h after operation in the oblique lateral fusion group 1.21±0.55 was significantly less than that in the posterior fusion group 1.70±0.86 ( t=3.723, P=0.028). The follow-up period lasted for 12-24 months, averagely 17.5±2.58 months. There was statistically significant difference between preoperative and postoperative in the two groups, whether it was the area of the foraminal canal or the area of the spinal canal. There wboth the foraminal area and the spinal canal area were enlarged. The intervertebral space height in the two groups recovered significantly after surgery, the difference was statistically significant. But the intervertebral space height were partly lost at the last follow-up, and there was significant difference compared with postoperative. During the follow-up, no pedicle screw loosening, displacement, rupture, or anterior and lateral displacement of cage occurred. The fusion rate was 97.1% in the posterior fusion group and 100% in the oblique lateral fusion group. There was no statistical difference between the two groups.In terms of ODI index: the posterior fusion group recovered from 48.6±6.1 preoperative to 10.2±2.2 at the last follow-up, and the oblique lateral fusion group recovered from 49.0±5.7 preoperative to 9.3±1.8 at the last follow-up. There was statistically difference between last follow-up and preoperative in the two groups. The incidence of complications in the posterior fusion group was 22.86%, and the incidence in the oblique lateral fusion group was 23.68%. There was no significant difference between the two groups. Conclusion:Both the two decompression and fusion methods have achieved good clinical results in the treatment of lumbar spinal stenosis, with the advantages of less trauma, good stability, fast recovery, and high fusion rate. Compared with posterior decompression and fusion methods, the advantages of OLIF are more obvious, such as less bleeding,lower risk of nerve injury and good indirect decompression of spinal canal. Therefore, the OLIF technique can be a better choice for surgical treatment of lumbar spinal stenosis.

Objective:To investigate the characteristics and causes of endplate injury in the oblique lateral interbody fusion for the treatment of lumbar diseases, and summarize the precaution of endplate injury.Methods:Thirty-five cases of endplate injury were observed, which were originally treated with oblique lateral interbody fusion with or without pedicle screw fixation from October 2014 to December 2017. There were 7 males and 28 females, and the age ranged from 51 to 78 years old (averagely 62.8±8.13 years). There were 2 cases of lumbar disc degeneration, 10 cases of lumbar canal stenosis, 17 cases of lumbar degenerative spondylolisthesis, 2 cases of lumbar spondylolysis with or without spondylolisthesis, and 4 cases of lumbar degenerative scoliosis. Lesion sites contained L 3,4 in 2 cases, L 4,5 in 21 cases, L 2-4 in 3 cases, L 3-5 in 4 cases, L 2-5 in 3 cases and L 1-5 in 2 cases. Preoperative bone mineral density examination revealed there were 7 cases of T>-1 SD, 24 cases of -2.5 SD