AIM:To evaluate visual outcomes and visual function in nonamblyopic adults with myopic anisometropia treated with small incision lenticule extraction(SMILE).METHODS:Prospective comparative cohort study. The consecutive patients who underwent SMILE for the treatment of myopia or myopic astigmatism at Zhongshan Ophthalmic Center(Guangzhou, China)between October 2015 and January 2016 were included. They were divided into two groups based on the bilateral difference of a spherical equivalent(SE)refraction ≥1.50 D: the anisometropic myopia group(interocular SE difference ≥1.50 D)and non-anisometropic myopia group(interocular SE difference<1.50 D). Refractive status, uncorrected and corrected distance visual acuity(UDVA and CDVA), and visual function parameters including fusional vergence amplitude, stereoacuity and horizontal phoria were measured preoperatively and at 1 wk,1,3 and 6 mo after surgery.RESULTS:A total of 49 cases(98 eyes)were included in the study, and 19 cases(38 eyes)in the anisometropic group, including 11 males and 8 females, with a mean age of 25.4±6.2 y, and 30 cases(60 eyes)in the non-anisometropic myopia group, including 19 males and 11 females, with a mean age of 26.8±4.6 y. The CDVA of the non-anisometropia group was significantly better than that of the anisometropia group 6 mo postoperatively(P=0.036). However, the safety and efficacy indexes of the two groups did not show significant differences. The fusional vergence(break point and recovery point)of the anisometropia group decreased(P=0.005 and P=0.03)and was significantly lower than that in the non-anisometropia group at 6 mo post operatively(P=0.029 and P=0.046). Both groups showed a significant improvement in distance and near stereopsis at 1, 3 and 6 mo in comparison with the preoperative baseline and 1 wk postoperatively(all P<0.05). No clinically significant change in the amount of ocular alignment in terms of distance and near deviation postoperatively in either groups.CONCLUSION: SMILE is a predictable, effective, and safe method for correcting myopic anisometropia in adults without amblyopia. Although the fusional vergence amplitudes changed, stereopsis can be improved after surgery.

OBJECTIVE To investigate the ameliorative effect and mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway. METHODS The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice. RESULTS In vitro results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （ P ＜0.05）. In vivo results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （ P ＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜0.05）. CONCLUSIONS Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury.

OBJECTIVE:In recent years,resistance exercise therapy as a means of rehabilitation has attracted much attention,but its therapeutic effect on cervical radiculopathy is still controversial.This study evaluated the clinical efficacy of resistance exercise in the treatment of cervical radiculopathy through a systematic meta-analysis.METHODS:A comprehensive search was conducted in CNKI,VIP,WanFang,Chinese Biomedical Literature Database,PubMed,Web of Science,Cochrane Library and Embase for clinical randomized controlled trials related to resistance exercise in the treatment of cervical radiculopathy.The search time was from the establishment of each database to November 30,2024.The resistance training group(experimental group)used resistance exercise or resistance exercise as the main intervention method.The control group received other rehabilitation therapy except resistance exercise.Outcome measures included total effective rate,visual analog scale score,Neck Disability Index,Tanaka Symptom Scale for Cervical Spondylosis,cervical joint motion,and recurrence rate.Cochrane bias risk assessment tool and physical therapy evidence database scale were used to determine the quality of the included references.Meta-analysis was performed using RevMan 5.4 software and Stata 17.0.RESULTS:(1)Finally,9 RCTs were included,including a sample size of 673 cases.GRADE evidence quality evaluation showed that the total effective rate was medium level of evidence,while visual analog scale score,Neck Disability Index,Tanaka Symptom Scale for Cervical Spondylosis score,joint motion,and recurrence rate were low level of evidence.(2)The results of meta-analysis showed that the total effective rate in the experimental group was higher than that in the control group(RR=1.22,95％confidence interval[CI]=1.06-1.41,P=0.005).(3)The visual analog scale score in the experimental group was better than that in the control group(mean difference[MD]=-0.72,95％CI=-0.98 to-0.46,P＜0.000 01).The Neck Disability Index in the experimental group was better than that in the control group(MD=-2.57,95％CI=-4.13 to-1.02,P=0.001).The Tanaka Symptom Scale for Cervical Spondylosis score in the experimental group was better than that in the control group(MD=3.83,95％Cl=3.55-4.10,P＜0.000 01).Cervical joint motion:the anterior flexion joint motion of the experimental group was better than that of the control group(MD=2.86,95％CI=2.30-3.43,P＜0.000 01);the posterior extension joint motion of the experimental group was better than that of the control group(MD=5.23,95％CI=3.81-6.64,P＜0.000 01).The range of motion of the left rotator joint in the experimental group was better than that in the control group(MD=7.15,95％CI=5.43-8.87,P＜0.000 01);the range of motion of the right rotator joint in the experimental group was better than that in the control group(MD=5.45,95％CI=3.59-7.31,P＜0.000 01).The range of motion of the left flexion joint in the experimental group was better than that in the control group(MD=3.35,95％CI=1.98-4.72,P＜0.000 01);the range of motion of the right flexion joint in the experimental group was better than that in the control group(MD=3.91,95％CI=2.65-5.17,P＜0.000 01).The recurrence rate in the experimental group was lower than that in the control group(RR=0.22,95％CI=0.06-0.80,P=0.02).CONCLUSION:Resistance exercise can effectively improve the pain of patients with cervical radiculopathy,promote the recovery of cervical vertebra function and reduce the recurrence rate.However,the evidence level of the methodological quality and outcome indicators of the included studies is low,and more high-quality and large-sample randomized controlled trials are needed for further research and confirmation in the future.

OBJECTIVE:In recent years,resistance exercise therapy as a means of rehabilitation has attracted much attention,but its therapeutic effect on cervical radiculopathy is still controversial.This study evaluated the clinical efficacy of resistance exercise in the treatment of cervical radiculopathy through a systematic meta-analysis.METHODS:A comprehensive search was conducted in CNKI,VIP,WanFang,Chinese Biomedical Literature Database,PubMed,Web of Science,Cochrane Library and Embase for clinical randomized controlled trials related to resistance exercise in the treatment of cervical radiculopathy.The search time was from the establishment of each database to November 30,2024.The resistance training group(experimental group)used resistance exercise or resistance exercise as the main intervention method.The control group received other rehabilitation therapy except resistance exercise.Outcome measures included total effective rate,visual analog scale score,Neck Disability Index,Tanaka Symptom Scale for Cervical Spondylosis,cervical joint motion,and recurrence rate.Cochrane bias risk assessment tool and physical therapy evidence database scale were used to determine the quality of the included references.Meta-analysis was performed using RevMan 5.4 software and Stata 17.0.RESULTS:(1)Finally,9 RCTs were included,including a sample size of 673 cases.GRADE evidence quality evaluation showed that the total effective rate was medium level of evidence,while visual analog scale score,Neck Disability Index,Tanaka Symptom Scale for Cervical Spondylosis score,joint motion,and recurrence rate were low level of evidence.(2)The results of meta-analysis showed that the total effective rate in the experimental group was higher than that in the control group(RR=1.22,95％confidence interval[CI]=1.06-1.41,P=0.005).(3)The visual analog scale score in the experimental group was better than that in the control group(mean difference[MD]=-0.72,95％CI=-0.98 to-0.46,P＜0.000 01).The Neck Disability Index in the experimental group was better than that in the control group(MD=-2.57,95％CI=-4.13 to-1.02,P=0.001).The Tanaka Symptom Scale for Cervical Spondylosis score in the experimental group was better than that in the control group(MD=3.83,95％Cl=3.55-4.10,P＜0.000 01).Cervical joint motion:the anterior flexion joint motion of the experimental group was better than that of the control group(MD=2.86,95％CI=2.30-3.43,P＜0.000 01);the posterior extension joint motion of the experimental group was better than that of the control group(MD=5.23,95％CI=3.81-6.64,P＜0.000 01).The range of motion of the left rotator joint in the experimental group was better than that in the control group(MD=7.15,95％CI=5.43-8.87,P＜0.000 01);the range of motion of the right rotator joint in the experimental group was better than that in the control group(MD=5.45,95％CI=3.59-7.31,P＜0.000 01).The range of motion of the left flexion joint in the experimental group was better than that in the control group(MD=3.35,95％CI=1.98-4.72,P＜0.000 01);the range of motion of the right flexion joint in the experimental group was better than that in the control group(MD=3.91,95％CI=2.65-5.17,P＜0.000 01).The recurrence rate in the experimental group was lower than that in the control group(RR=0.22,95％CI=0.06-0.80,P=0.02).CONCLUSION:Resistance exercise can effectively improve the pain of patients with cervical radiculopathy,promote the recovery of cervical vertebra function and reduce the recurrence rate.However,the evidence level of the methodological quality and outcome indicators of the included studies is low,and more high-quality and large-sample randomized controlled trials are needed for further research and confirmation in the future.

OBJECTIVE To establish a method for simultaneous determination of venetoclax， busulfan and voriconazole in plasma of patients with acute myeloid leukemia （AML）， and apply it clinically. METHODS Plasma samples were subjected to protein precipitation using acetonitrile and subsequently analyzed by liquid chromatography-tandem mass spectrometry （LC-MS/MS） using venetoclax-D 8 ， busulfan-D 8 and posaconazole as internal standards. The separation was performed on a Phenomenex Kinetex ® C 18 column with a mobile phase composed of 0.1% formic acid solution （2 mmol/L ammonium acetate）-0.1% formic acid in acetonitrile （gradient elution） at a flow rate of 0.8 mL/min. The column temperature was set at 40 ℃， the sample size was 5 μL， and the total run time was 3.10 min. An electrospray ionization source was employed， and positive ion scanning was conducted using multiple reaction monitoring mode. The ion pairs used for quantitative analysis included m/z 868.4→636.3 （venetoclax）， m/z 264.1→151.1 （busulfan）， and m/z 350.1→224.0 （voriconazole）. The above LC-MS/MS method was adopted to determine plasma concentrations of venetoclax and voriconazole in 10 AML patients， as well as plasma concentration of busulfan in 5 patients undergoing conditioning treatment for allogeneic hematopoietic stem cell transplantation. RESULTS The linear ranges of venetoclax， busulfan and voriconazole were 50-10 000， 15-3 000 and 50-10 000 ng/mL， respectively （ R 2 ≥0.999 0）， with lower limits of quantification of 50， 15 and 50 ng/mL， respectively. The RSDs of intra-day and inter-day precision tests for all three analytes were all less than 10%， with accuracy （relative errors） ranging from －10.00% to 12.96%. The average extraction recovery ranged from 92.54% to 100.95%， and the average matrix effect was 89.98%-101.49%. Dilution reliability covered all dilution factors used in the test samples， and the absolute values of relative errors in stability tests were all≤16.25%. The plasma concentrations of venetoclax， busulfan and voriconazole in enrolled patients were 496.20-4 250.45， 233.48-2 002.28 and 475.51-5 710.18 ng/mL， respectively. CONCLUSIONS The LC-MS/MS method established in this study is rapid， sensitive and easy to operate， and can be used for the therapeutic drug monitoring of venetoclax， busulfan and voriconazole.

OBJECTIVE To explore the therapeutic efficacy and mechanism of oridonin （ORI） against obesity-related glomerulopathy （ORG） based on the liver X receptor α （LXRα） signaling pathway. METHODS Kidney tissues of LXRα wild-type homozygous （LXRα+/+） mice and LXRα homozygous knockout （LXRα－/－） mice were subjected to high-throughput renal transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict key pathways and targets regulated by LXRα， followed by verification via Western blot assay. An ORG mouse model was established by feeding a high-fat diet. The LXRα agonist GW3965 （30 mg/kg） was set as the positive control. After intragastric administration of 50 mg/kg and 100 mg/kg ORI once daily for 4 consecutive weeks， the body weight， renal weight， renal histopathological alterations， serum renal function indicators， blood lipid levels and inflammatory factor levels in renal tissue of mice were detected and observed to evaluate the efficacy of ORI in alleviating ORG. Meanwhile， the mRNA and protein expression levels of LXRα and its downstream targets in mouse renal tissues were detected to validate the mechanism by which ORI relieves ORG. RESULTS Compared with LXRα+/+ mice， the upregulated differentially expressed genes in renal tissues of LXRα－/－ mice were significantly enriched in the arachidonic acid（AA） metabolic pathway， and the expression level of Cyp4a12 was markedly elevated （adjusted P＜0.05）. Western blot results verified that cytochrome P450 family 4 subfamily A member 12（CYP4A12）protein expression was significantly increased in the kidneys of LXRα－/－ mice （P＜0.05）. Pharmacodynamic results showed that both 50 mg/kg and 100 mg/kg ORI notably improved renal pathological lesions in ORG mice； these two doses reduced body weight， renal weight， serum creatinine， blood urea nitrogen， blood lipid levels as well as renal interleukin-6 （IL-6） and IL-1β levels （P＜0.05）. In addition， ORI significantly upregulated the mRNA and protein expression of renal nuclear LXRα and ABCA1， and downregulated the mRNA and protein expression of CYP4A12（P＜0.05）. CONCLUSIONS ORI may exert an ameliorative effect on ORG by activating the LXRα signaling pathway， downregulating CYP4A12 expression， and inhibiting AA-induced inflammatory metabolism.

Cardiovascular diseases are the leading cause of mortality worldwide， yet their pathogenic mechanisms and functional repair remain incompletely understood. The emergence and development of human induced pluripotent stem cells （hiPSC） have provided unprecedented opportunities for cardiovascular disease research， and markedly enhanced our understanding of cardiovascular disease mechanisms. This review summarizes recent advances in cardiovascular cells and cardiac organoids derived from hiPSC， and presents our team's related research findings in this field. It highlights the induction and differentiation of hiPSC-derived cardiomyocytes and non-myocytes， as well as their roles in disease modeling， functional repair， drug screening， and mechanistic investigation. Furthermore， the current applications of hiPSC-derived cardiac organoids in cardiovascular disease research are also discussed.

ObjectiveTo investigate the temporal trend of weight-adjusted-waist index （WWI） and its association with the risk of incident cardiovascular diseases （CVD） among middle-aged and older Chinese adults. MethodsBased on the China Health and Retirement Longitudinal Study （CHARLS）， this research enrolled participants aged 45 and above with complete physical measurement data from the 2011， 2013， and 2015 waves. Complex sampling weights were applied to calculate the mean WWI， and the Mann-Kendall test was used to analyze its trend. From the 2011 baseline survey， individuals with a history of cardiovascular disease or missing key covariates were further excluded. New-onset cardiovascular outcome events were collected during follow-up until 2020. Participants were categorized into Q1–Q4 groups based on baseline WWI quartiles. Multivariable log-binomial regression models were constructed to assess the association between WWI and CVD， while restricted cubic splines were employed to evaluate potential nonlinear relationships. Sensitivity analyses were conducted to verify the robustness of the findings. ResultsFrom 2011 to 2015， the weighted mean WWI among Chinese middle-aged and older adults remained generally stable （2011： 11.17±1.68； 2013： 11.28±1.35； 2015： 11.24±1.59； P for trend <0.05）. During the longitudinal follow-up， 1 784 incident CVD cases were documented. After multivariable adjustment， each unit increase in WWI was associated with a 17% increased risk of CVD （RR： 1.17， 95%CI： 1.10-1.24）. Compared with the Q1 group， the risk of CVD in the Q2， Q3， and Q4 groups increased by 23% （RR： 1.23， 95% CI： 1.07-1.40）， 27% （RR： 1.27， 95% CI： 1.11-1.44）， and 40% （RR： 1.40， 95% CI： 1.22-1.60）， respectively. A significant linear trend was observed between the increasing WWI and elevated CVD risk （P for trend <0.001）. Subgroup analysis revealed a stronger association in participants aged 45-60 years （P for interaction <0.05）. The results of sensitivity analysis were consistent with the main research results. ConclusionsThe overall trend of WWI level in the middle-aged and elderly population in China is stable from 2011 to 2015. The higher level of WWI is associated with an increased risk of CVD， suggesting that WWI may be used as a simple and effective indicator to evaluate the risk of cardiovascular metabolism in middle-aged and elderly people.

ObjectiveTo enhance the genetic diagnostic yield for fetal short femur length （FL） and to evaluate the integration of whole exome sequencing （WES） with chromosomal abnormality detection in prenatal diagnosis. MethodsA total of 27 mid-to-late trimester fetuses diagnosed with short FL ［FL < 5th percentile for gestational age or < -2 SD （Standard Deviation）］ at the Prenatal Diagnosis And Medical Genetics Center，Shenshan Medical Center，Memorial Hospital of Sun Yat-Sen University between November 2023 and May 2025 were included. Amniotic fluid or umbilical cord blood samples were collected and subjected to chromosomal karyotyping （19cases）， chromosomal microarray analysis （CMA） or low-coverage whole genome copy number variation（CNV-Seq） （27 cases）， and trio-based whole exome sequencing （trio-WES） （27 cases）. The pathogenicity of genetic variants were interpreted according to the American College of Medical Genetics and Genomics （ACMG） guidelines. ResultsTwenty-six genomic variants were detected in 17 of the 26 fetuses， including numerical chromosomal abnormalities （mosaic type）， copy number variations （CNVs）， single nucleotide variants （SNVs） and insertions-deletions （INDELs）. Genomic variants detected in 11 cases could explain the short femur phenotype.The overall diagnostic rate was 11/27， with pathogenic/likely pathogenic variants explaining 9 cases and variants of uncertain significance （VUS） accounting for 1 cases. In addition Chromosomal karyotype analysis revealed chromosome mosaicism explaining 1 case. The diagnostic rate of CNV detection （CMA/CNV-seq） was 2/27， while WES achieved a diagnostic rate of 10/27， with an incremental yield of 8/27 in cases with negative or inconclusive CNV results. Pathogenic mutations involved genes such as FGFR3， SHOX， DUOX2， CLCN5， and HBA1/HBA2. ConclusionTrio-WES significantly improves the genetic diagnostic rate for fetal short femur length， particularly in cases where chromosomal analysis fails to identify a cause. Karyotyping remains valuable for detecting low-level mosaicism in large-scale chromosomal abnormalities， thereby complementing WES and CNV detection. A stepwise or parallel genetic testing strategy is recommended in prenatal diagnosis to optimize diagnostic efficiency and support clinical decision-making.

Objective To investigate the therapeutic effects and underlying mechanisms of Ganluqingwen formula on lipopolysaccharide(LPS)-induced acute lung injury/acute respiratory distress syndrome(ALI/ARDS)in mice.Methods Fifty ICR mice were randomly divided into five groups:control,model,and Ganluqingwen formula(GLQW)low dose(7.10 g/kg),medium dose(15.21 g/kg),and high dose(30.42 g/kg)groups,with 10 mice per group.On days 1-3,mice in GLQW groups were daily gavaged with the corresponding dose of GLQW,while control and model groups received equal volumes of saline.On day 4,ALI/ARDS was induced in model and GLQW groups using intraperitoneal injection of LPS(20 mg/kg),while control group received an equal volume of PBS.At 24 h post-treatment,survival rate,wet-to-dry weight ratio(W/D)and lung histological changes(HE staining)were observed.Serum levels of tumor necrosis factor(TNF)-α,interferon gamma(IFN-γ),interleukin(IL)-4,IL-10,IL-12,as well as lung tissue levels of TNF-α,IFN-γ,IL-1β,IL-4,IL-6,IL-10 were measured by ELISA.Western blotting was used to determine the expression levels of NOD-like receptor thermal protein domain associated protein 3(NLRP3),cystatinase-1(Caspase-1),apoptosis-associated speck-like protein(ASC),and membrane perforating protein Gasdermin D(GSDMD)in lung tissue.Results No significant differences in survival rates were observed among the groups(P>0.05).Compared with control group,ELISA and Western blotting results showed that lung tissue W/D,IFN-γ,TNF-α,IL-4,IL-12,IL-1β,IL-6,NLRP3,ASC,and Caspase-1,GSDMD and serum IFN-γ,TNF-α,IL-4,IL-12 levels were significantly higher(P<0.05),and IL-10 levels in lung tissue and serum were significantly lower in mice of model group(P<0.05).Compared with model group,lung tissue W/D,IFN-γ,TNF-α,IL-1β,IL-4,IL-6,IL-12,NLRP3,ASC,Caspase-1,and GSDMD,and serum IFN-γ,TNF-α,IL-4,and IL-12 levels were significantly lower(P<0.05),and lung tissue IL-10 levels were significantly higher(P<0.05)in GLQW low,medium,and high dose groups,with high-dose group showing significantly higher level in serum IL-10(P<0.05).Compared with GLQW low-dose group,the lung tissue levels of IFN-γ,IL-6,NLRP3,ASC,Caspase-1,and GSDMD,and serum TNF-α were significantly lower(P<0.05),and lung and serum IL-10 levels were significantly higher in GLQW high-dose group(P<0.05).HE staining results showed that lung structure was clear and normal in control group;part of the lung interstitium was congested and hemorrhagic,and some of the fine bronchial periphery was infiltrated with inflammatory cells in model group;the phenomena of lung interstitial congestion and hemorrhage were reduced,and the degree of infiltration of inflammatory cells was alleviated in GLQW low-,medium-,and high-dose groups.Conclusion Ganluqingwen formula can delay the development of ALI/ARDS in mice by inhibiting NLRP3/Caspase-1/GSDMD pathway,thereby suppressing cellular pyroptosis.