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.

Objective:To explore the effects of Tongdu Tiaoshen acupuncture on vascular endothelial function and inflammatory factors in patients with mild cognitive impairment (MCI) after ischemic stroke (IS).Methods:A retrospective analysis was performed on the clinical data of 71 patients with MCI after IS in the hospital between January 2020 and September 2022. According to different treatment methods, they were divided into Tongdu Tiaoshen acupuncture group ( n=31, Tongdu Tiaoshen acupuncture + oral nimodipine tables) and routine body-acupuncture group ( n=40, routine body-acupuncture group + oral nimodipine tables). Both groups were treated for 2 courses (14 d/course). Before and after treatment, levels of serum NO and endothelin-1 (ET-1) were detected by radioimmunoassay, and levels of serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), plasma homocysteine (Hcy) and IL-6 were detected by ELISA. The cognitive function of patients was evaluated and intelligence level by Montreal Cognitive Assessment Scale (MoCA), Mini-Mental State Examination(MMSE) and the clinical curative effect was also evaluated. Results:The total response rates in Tongdu Tiaoshen acupuncture group and routine body-acupuncture group were 90.32% (28/31) and 70.00% (28/40), and the difference between the two groups was statistically significant ( χ2=4.33, P=0.037). After treatment, levels of plasma Hcy and IL-6 in Tongdu Tiaoshen acupuncture group were lower than those in the routine body-acupuncture group ( t=2.57, 9.36, P<0.05 or P<0.01). After treatment, levels of serum bFGF, VEGF and NO in Tongdu Tiaoshen acupuncture group were significantly higher than those in the routine body-acupuncture group ( t=10.03, 9.29, 8.17, P<0.01), while ET-1 level was significantly lower than that of the routine body-acupuncture group ( t=2.41, P=0.019). After treatment, MoCA score [(28.24±4.45) vs. (25.32±4.34), t=2.78], MMSE score [(28.73±1.44) vs. (28.02±1.22), t=2.25] in Tongdu Tiaoshen acupuncture group were higher than those in the routine body-acupuncture group ( P<0.01). Conclusion:Tongdu Tiaoshen acupuncture is beneficial to improve vascular endothelial function, reduce levels of inflammatory factors, promote the recovery of cognitive function and improve curative effect in patients with MCI after IS.

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 explore the role of arginine metabolism in the inflammatory response to influenza A virus (FluA) infection.Methods:Eighteen-month-old mice were infected with FluA via nasal drip, with samples collected on the 6th day post-infection. The concentration of cytokines was determined by the Luminex multifactor assay, while the metabolites in bronchoalveolar lavage fluid (BALF) were analyzed using targeted metabolomic method. Correlation analysis was employed to examine the correlation between cytokines and metabolites. Macrophages were infected with FluA at a multiplicity of infection (MOI) of 1 and cultured with different concentrations of arginine for 24 h. The mRNA and protein expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α) and IL-10 were detected by real time fluorescence quantitative RT-PCR (qRT-PCR) and Cytometric Bead Array (CBA).Results:In comparison to the control group, the levels of surfactant protein D (SP-D), TNF-α, monocyte chemotactic protein-1 (MCP-1), IL-1α, IL-6, IL-10, recombinant S100 calcium binding protein (S100) A9, interferon inducible protein 10 (IP-10), macrophage inflammatory protein-1α (MIP-1α), matrix metalloprotein-9 (MMP-9), and Complement Factor D in BALF of FluA infection exhibited a significant elevation. The concentrations of arginine, aspartate, citrulline, glutamic acid, ornithine, proline, creatine, and sarcosine in arginine metabolism were up-regulated, which was correlated with most of elevated cytokine levels. The supplementation of arginine after FluA infection significantly decreased the levels of IL-1β, IL-6, and TNF-α, but increased the level of IL-10 in macrophages.Conclusions:Arginine reduces the inflammatory response induced by FluA infection in macrophages, suggesting that it may be a potential intervention target for severe pulmonary inflammation following FluA infection.

Immunotherapy modulates immune response and corrects cancer-immune cycle, controlling the tumors persistently. With the development of clinical and pre-clinical research, immunotherapy is reshaping the landscape of systematic treatment on breast cancer. However, numerous unknowns and challenges persist. This review aims to comprehensively overview the latest research progress in immunotherapy of breast cancer from mechanistic and clinical efficacy perspectives, as well as to summarize unresolved issues, offering new avenues for precision treatment of breast cancer.

OBJECTIVE To evaluate the short-term efficacy of single-session microwave ablation for benign thyroid nodule.METHODS Patients with benign thyroid nodules treated by microwave ablation between June 2019 and December 2022 at the Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,were included for analysis.Thyroid function was tested 1 month after treatment,and ultrasound and thyroid function were performed 3 months,6 months and 1 year after treatment.Volume reduction rates(VRR)of nodules were calculated.Data of the last follow-up within 1 year were included for analysis.Variables including gender,age,whether Hashimoto's thyroiditis was present,longitudinal diameter of nodules,solid volume of nodules were included for univariate and multivariate analysis.RESULTS A total of 151 patients with 163 nodules were included.The perioperative complication rate was 1.99%(3/151).The VRR at half year after treatment was(79.58±17.70)%,and the success rate at half year after treatment was 93.43%(128/137).The VRR of at 1year after treatment was(81.24±24.29)%.The 1-year treatment success rate was 92.77%(77/83).Univariate and multivariate analysis showed that nodular solid volume and age were independent factors affecting VRR after ablation.Regression coefficient of age and solid volume was 0.34(P<0.05)and-0.47(P<0.05),respectively.For every 1 cm3 increase in solid volume,1-year VRR(%)decreased by 0.47.Regression equation:1-year VRR=68.92+0.34×age-0.47×solid volume.Serum FT4 gradually decreased and the thyroid stimulating hormone(TSH)gradually increased within 6 months after ablation,and the differences were statistically significant(P<0.05).After 6 months,serum FT4 gradually recovered to the normal level and TSH gradually recovered.However,TSH still did not reach the preoperative level one year after ablation.FT3 decreased gradually after treatment,but there was no significant difference between the values at each time point(P=0.40).After the ablation of thyroid nodule,the mean value of thyroid function index fluctuated,but all of them were within the normal reference range.CONCLUSION Microwave ablation is a safe and effective treatment method for benign thyroid nodules,with an overall success rate of over 90%.Solid nodule volume and age are independent factors affecting the microwave ablation effect of benign thyroid nodules.

Aflatoxin B1(AFB1)is a secondary metabolite produced by Aspergillus aflatoxin and Aspergillus parasiticus.It has strong immunotoxicity and carcinogenicity and seriously harms the health of humans and livestock.Therefore,this study aims to explore the effect of selenomethionine(SeMet)in alleviating AFB1-induced thymic damage.Fifty 35-day-old rabbits were randomly divid-ed into 5 groups,with 10 rabbits in each group.They are the control group,AFB1 group,AFB1+0.2Se group(0.2 mg/kg SeMet),AFB1+0.4Se group(0.4 mg/kg SeMet)and AFB1+0.6Se group(0.6 mg/kg SeMet).The test period was 21 d.On the 17th day,each rabbit in the AFB1 group and each SeMet group was gavaged with AFB1(0.3 mg/kg)every day for 5 consecutive days.Rabbit thymus tissue was taken for HE,TUNEL and PCNA detection.ELISA was used to detect the ex-pression of inflammatory factors in thymus tissue,and GSH-Px,T-AOC and MDA kits were used to detect oxidative stress indicators in thymus tissue.The results showed that AFB1 exposure caused a very significant increase in MDA levels in rabbit thymus tissue by 116.04％,and a signifi-cant decrease in the activities of antioxidant enzymes GSH-Px and T-AOC by 29.20％and 52.17％respectively.In addition,AFB1 induced an inflammatory response in the thymus,promoting TNF-a secretion to increase by 124.71％,IL-6 by 174.72％,and IL-1β by 62.38％compared with the con-trol group.SeMet pretreatment significantly improved the pathological changes of the thymus in rabbits and reduced its oxidative stress and inflammatory response.Therefore,we confirmed that SeMet alleviates AFB1-induced thymic damage and improves the immune performance of rabbits.

Objective:To investigate the clinical value of spherical lens with 0.05 D intervals in optometry for small incision lenticule extraction (SMILE) in myopic eyes.Methods:A randomized controlled clinical study was conducted.Sixty patients (120 eyes) with low to moderate myopia and myopic astigmatism who underwent SMILE in the 989th Hospital of the PLA from June 2021 to February 2022 were enrolled.The patients were randomly divided into 0.05 D interval group (optometry with spherical lens at 0.05 D interval) and 0.25 D interval group (optometry with spherical lens at 0.25 D interval), with 30 cases (60 eyes) in each group.There was no significant difference in matched age, sphericity, cylindricity, and best corrected visual acuity (BCVA) (all at P>0.05). The preoperative monocular red-green balance, 1- and 3-month postoperative monocular red-green balance, uncorrected visual acuity and spherical equivalent of both groups were compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the 989th Hospital of the PLA (No.WZLL-2021-034). Written informed consent was obtained from each subject before any medical examination. Results:The preoperative red-green balance rate in 0.05 D interval group was 95.00%(57/60), which was higher than 35.00%(21/60) in 0.25 D interval group, showing a statistically significant difference ( Wald χ2=17.642, P<0.001). The 1- and 3-month postoperative red-green balance rates in 0.05 D interval group were 63.33%(38/60) and 56.67%(34/60), which were higher than 23.33%(14/60) and 21.67%(13/60) in 0.25 D interval group respectively, showing statistically significant differences ( Wald χ2=9.137, P=0.003; Wald χ2=7.483, P=0.006). The 1- and 3-month postoperative visual acuity in 0.05 D interval group were -0.1(-0.1, -0.1) and -0.1(-0.1, -0.1), which were higher than 0.0(-0.1, 0.0) and -0.1(-0.1, 0.0) in 0.25 D interval group respectively, showing statistically significant differences ( Wald χ2=11.624, P=0.001; Wald χ2=12.841, P<0.001). The 1- and 3-month postoperative spherical equivalent were -0.07(-0.25, 0.13)D and -0.13(-0.25, 0.13)D in 0.05 D interval group, which were higher than -0.13(-0.38, 0.25)D and -0.13(-0.38, 0.25)D in 0.25 D interval group respectively, showing no statistically significant difference between the two groups ( Wald χ2=0.029, P=0.866; Wald χ2=0.189, P=0.664). Conclusions:Compared with spherical lens at 0.25 D interval, 0.05 D interval can improve the accuracy of preoperative and postoperative red-green balance rate and postoperative visual acuity in patients with low to moderate myopia who undergo SMILE.

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.

OBJECTIVE: To analyze the clinical features of a Chinese pedigree affected with tuberculosis sclerosis and explore its molecular pathogenesis. METHODS: Clinical data of the proband and members of his pedigree were collected. Whole exome sequencing was carried out to detect variants of the TSC1 and TSC2 genes. Candidate variants was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband and his mother, who also had mild features of tuberous sclerosis, were found to harbor a novel heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene, which was absent in the 4 healthy relatives. Bioinformatic analysis suggested the variant to be likely pathogenic. CONCLUSION The heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene probably underlay the disease in this pedigree. Above finding has expanded the spectrum of TSC2 gene variants. The more severe symptoms in the proband may be attributed to phenotypic heterogeneity of this disease.
China ; Humans ; Mutation ; Pedigree ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*