1.Compact Fundus Imaging System Using Shack-Hartmann Wavefront Sensing for High-speed Auto-focus
Zhe-Kai LIN ; Long CHEN ; Geng-Yong ZHENG ; Jin-Tian HUANG ; Jia-Xin DONG ; Shang-Pan YANG ; Wen-Zheng DING ; Ding-An HAN ; Xue-Hua WANG ; Ya-Guang ZENG
Progress in Biochemistry and Biophysics 2026;53(4):1076-1086
ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.
2.Effects of resistance combined with aerobic chrono-exercise on common carotid artery elasticity and hemodynamics in young men.
Miao-Xin JIAO ; Bing-Yi SHEN ; Hai-Bin LIU ; Li-Hong CHEN ; Guang-Rui YANG
Acta Physiologica Sinica 2025;77(4):741-751
The purpose of the present study was to investigate the effects of resistance combined with aerobic chrono-exercise on the common carotid artery elasticity and hemodynamics. 24 healthy young men (21.96±0.43 years old) underwent a single acute resistance combined with aerobic exercise intervention at eight time periods (6, 8, 10, 12, 14, 16, 18, and 20 o'clock). The axial flow velocity and diameter waveforms of the common carotid artery were measured, and the hemodynamics were calculated using the classical hemodynamic theory before exercise, immediately after exercise, 10 min and 20 min after exercise. The results showed that during exercise recovery, systolic and mean pressures decreased more markedly after exercise at 8 o'clock (P < 0.05); At 20 min post-exercise, arterial stiffness index and pressure-strain elastic modulus after exercise at 6 o'clock were reduced compared with the resting state, but were significantly elevated after exercise at 20 o'clock (P < 0.05). Immediately after exercise, the pressure rise was higher after exercise at 6 o'clock and the mean wall shear stress was higher after exercise at 20 o'clock (P < 0.05). These results suggest that resistance combined with aerobic chrono-exercise produces different effects on common carotid artery hemodynamics in young men. A single acute session of resistance combined with aerobic exercise at 8 o'clock is more effective in lowering blood pressure. Exercise at 6 o'clock is beneficial to improve arterial elasticity but is not recommended for young male individuals with cardiovascular disease risks because of the excessive increase in blood pressure immediately after exercise. Exercise at 20 o'clock is more effective in improving wall shear stress but is accompanied by elevated arterial stiffness indices and pressure-strain elastic modulus. These results provide a scientific basis for healthy young men in choosing the time of exercise by exploring the common carotid artery elasticity and hemodynamic-related indices.
Humans
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Male
;
Young Adult
;
Exercise/physiology*
;
Carotid Artery, Common/physiology*
;
Hemodynamics/physiology*
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Vascular Stiffness/physiology*
;
Elasticity
;
Resistance Training
;
Adult
3.Correlation between arterial stiffness and incident chronic kidney disease among old adults taking health check-up
Guang YANG ; Xin SHEN ; Bokai CHENG ; Jiebin HOU ; Yabin ZHANG ; Hongyu CHEN ; Qingli CHENG ; Yansong ZHENG ; Jiahui ZHAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(9):1173-1178
Objective To investigate the correlation between arterial stiffness(AS)and incident chronic kidney disease(CKD)among the elderly individuals taking health checkup.Methods A retrospective study was conducted on 857 elderly individuals without CKD at baseline who taking physical exams in our medical center from December 2009 to May 2021.Their clinical and labora-tory data were collected.Brachial-ankle pulse wave velocity(baPWV)was used to assess the se-verity of AS,and then the subjects were divided into normal elasticity group(201 cases),and moderate(490 cases)and severe AS group(166 cases).Kaplan-Meier curves were plotted to dis-play cumulative incidence rates of incident CKD across different AS groups.Restricted cubic splines(RCS)and Cox regression models were applied to analyze the correlation of baPWV and incident CKD risk.Results The severe AS group had significantly advanced age,greater ratio of hypertension,larger waist circumference,higher HR,SBP and DBP,increased urinary albumin/creatinine ratio(UACR),elevated levels of TG and fasting blood glucose,and baPWV than the normal elasticity group(P<0.05).During the follow-up period,37 participants developed CKD.The incidence of CKD was obviously higher in the severe AS group than the normal arterial elas-ticity group(9.04%vs 3.48%).RCS analysis revealed a U-shaped relationship between baPWV and incident CKD risk.When baPWV ≥1 400 cm/s,each standard deviation increase in baPWV indicates the risk of incident CKD increasing by 71%(HR=1.71,95%CI:1.30-2.25,P<0.01).Regardless of adjustment for covariates or not,baPWV remained positive correlation with inci-dent CKD risk(P<0.05).Conclusion Among the elderly individuals undergoing health check-up,increased AS severity is significantly associated with higher risk of incident CKD when baP-WV ≥1400 cm/s.
4.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
5.Biomechanical Stability of Oblique Lumbar Interbody Fusion Combined With Lateral Plate Fixation Under Different Bone Conditions:a Finite Element Study
Zhiqiang WANG ; Xin PENG ; Yuanbo WANG ; Chongyu WANG ; Guang YANG ; Hongqiang WANG ; Yanzheng GAO
Chinese Journal of Minimally Invasive Surgery 2025;25(9):557-565
Objective To clarify the biomechanical properties of oblique lumbar interbody fusion(OLIF)combined with lateral plate(LP)fixation under different bone conditions by means of finite element(FE)analysis,so as to provide mechanical basis for clinical practice.Methods The three-dimensional nonlinear L3_5 FE model of the spine was constructed.Different material properties were assigned to each part of the model to establish a model of normal bone(NB),osteopenia(OS)and osteoporosis(OP)of the lumbar spine.OLIF combined with the following three internal fixation models were established.For NB,there were OLIF alone(M0),OLIF+LP fixation(M1),and OLIF+bilateral pedicle screw(BPS)fixation(M2);for OS,there were OLIF alone(N0),OLIF+LP fixation(N1),and OLIF+BPS fixation(N2);for OP,there were OLIF alone(P0),OLIF+LP fixation(P1),and OLIF+BPS fixation(P2).A 500 N load was applied on the upper surface of L3 to represent the weight of the upper body,and a 7.5 N·m moment was used to simulate the vertebral motion under six different conditions:flexion(FL),extension(EX),left bending(LB),right bending(RB),left rotation(LR)and right rotation(RR).The range of motion(ROM)of the fixed segment of NB,OS and OP models was calculated,and the overall stress of the vertebral body,the stress of the cage and the internal fixation device were recorded.Results Compared with the complete model,the stability of each surgical model increased.Compared with M0,ROM of M1 decreased,especially in the LB and RB,which was roughly equivalent to the stability of BPS but weaker than BPS in the control FL and EX direction.The situation in OS and OP model was similar to that in NB.Under the same internal fixation,L4_5 ROM gradually increased with bone deterioration.The overall intervertebral ROM of N1 in the FL direction increased by 16.1%compared with M1,P1 in the FL direction increased by 32.1%compared with M1,and P1 in the FL direction increased by 19.0%compared with N1.With the increase of posterior internal fixation,the overall stress of vertebral body,Cage and internal fixation stress showed a downward trend.Under the same internal fixation,with the loss of bone mass,the overall stress of the model gradually increased.Compared with M0,P0 increased the most in LR,reaching 56.5%.In the NB and OS models,the peak stress of the LP fixation under FL exceeded the minimum yield strength of the material by 22.7%and 33.8%,respectively,and was less than the minimum fatigue strength and yield strength of the material under the rest of the motion.In the OP,the peak stress of the internal fixation exceeded the minimum fatigue strength of the material at FL and EX,and reached 53.3%(>50%)at FL.Conclusions Under NB and OS,OLIF combined with LP fixation can significantly improve the stability of the surgical segment,especially in LB and RB directions,and the overall stability is weaker than that of BPS fixation.Under OP,FL and EX may increase the risk of internal fixation failure.Combination with BPS fixation should be considered to improve the safety of fixation.
6.Evidence evaluation of 12 commonly-used Chinese patent medicines in treatment of osteoporosis based on Eff-iEC and GRADE.
Guang-Cheng WEI ; Zhi-Long ZHANG ; Xin-Wen ZHANG ; Ye LUO ; Jin-Jie SHI ; Rui MA ; Jie-Yang DU ; Ke ZHU ; Jiu-Cheng PENG ; Yu-Long YA ; Wei CAO
China Journal of Chinese Materia Medica 2025;50(15):4372-4385
This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use*
;
Osteoporosis/drug therapy*
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Humans
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Nonprescription Drugs/therapeutic use*
;
Evidence-Based Medicine
;
Medicine, Chinese Traditional
7.Exploring urban versus rural disparities in atrial fibrillation: prevalence and management trends among elderly Chinese in a screening study.
Wei ZHANG ; Yi CHEN ; Lei-Xiao HU ; Jia-Hui XIA ; Xiao-Fei YE ; Wen-Yuan-Yue WANG ; Xin-Yu WANG ; Quan-Yong XIANG ; Qin TAN ; Xiao-Long WANG ; Xiao-Min YANG ; De-Chao ZHAO ; Xin CHEN ; Yan LI ; Ji-Guang WANG ; FOR THE IMPRESSION INVESTIGATORS AND COORDINATORS
Journal of Geriatric Cardiology 2025;22(2):246-254
BACKGROUND:
Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese.
METHODS:
Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics.
RESULTS:
The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05).
CONCLUSIONS
In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.
8.Effectiveness of Acupuncture in Improving Quality of Life for Patients with Advanced Cancer: A Systematic Review and Meta-Analysis.
Xin YU ; Si-Yao GONG ; Qin LUO ; Gui-Xing XU ; Hao TIAN ; Qian LI ; Ming CHEN ; Sha YANG ; Shu-Guang YU
Chinese journal of integrative medicine 2025;31(4):360-371
OBJECTIVE:
To investigate the effect of acupuncture on advanced cancer patients by meta-analysis.
METHODS:
Nine databases (the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure, the Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and WanFang Data) were searched for randomized controlled trials (RCTs) on acupuncture in advanced cancer patients published from inception to February 13, 2023 and updated to June 1, 2023. Primary outcomes were quality of life (QOL), while secondary outcomes were pain, fatigue, and adverse events (side effects). Data synthesis was performed using RevMan V.5.3 to calculate pooled effect sizes. RoB-2 was used for the risk of bias, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool.
RESULTS:
Totally 17 RCTs involving 1,178 participants were included, 15 of which were pooled for meta-analysis. Most studies demonstrated some concern for the overall risk of bias. The pooled data indicated that acupuncture was associated with improved QOL [mean difference (MD)=6.67, 95% confidence interval (CI): 5.09 to 8.26], pain (MD=-1.18, 95% CI -2.28 to -0.08), and adverse events (risk ratio=0.30, 95% CI: 0.26 to 0.57) compared with control groups. Fatigue outcome was not included. Heterogeneity was substantial, and GRADE evidence was very low for both QOL and pain.
CONCLUSIONS
Acupuncture could benefit patients with advanced cancer and is considered safe compared with usual care. However, the evidence regarding QOL and pain outcomes requires further validation. It is crucial to encourage the development of high-quality studies to strengthen this evidence. (Registry No. CRD42023423539).
Humans
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Acupuncture Therapy
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Neoplasms/therapy*
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Quality of Life
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Randomized Controlled Trials as Topic
;
Treatment Outcome
9.Clinical observation of different doses of metformin in the prevention and treatment of risperidone-induced metabolic syndrome in patients with schizophrenia
Jiao WU ; Guang YANG ; Xin WANG
Journal of Navy Medicine 2025;46(3):297-301
Objective To investigate the clinical effect of different doses of metformin on risperidone-induced metabolic syndrome in patients with schizophrenia.Methods A total of 77 patients with schizophrenia who were admitted to the Third People's Hospital of Tongling City from January 2017 to December 2021 were enrolled.All the patients were treated with metformin and risperidone.According to the dose of metformin,they were assigned to group A(n=32)and group B(n=45).Group A was given metformin 0.5 g/d(0.25 g each time,twice a day),and group B was given metformin 0.75 g/d(0.25 g each time,3 times a day).After 8 weeks of continuous administration,the clinical efficacy was evaluated according to the total score of the scale for assessment of positive symptoms(SAPS)and the scale for assessment of negative symptoms(SANS).The body weight and glucolipid metabolism indexes were compared between patients with different doses of metformin.The safety of treatment was recorded.Results The total effective rate of group B was 95.56%(43/45),which was higher than that of group A(78.13%[25/32],P<0.05).After treatment,the fasting blood glucose(FBG)level decreased and body mass index(BMI)and waist circumference increased in group A,FBG level decreased and waist circumference increased in group B.The FBG,BMI and waist circumference in group A were higher than those in group B after treatment(P<0.05).Triacylglycerol(TG)and total cholesterol(TC)in group A and TG in group B increased after treatment,and the levels of TG and TC in group A were higher than those in group B(P<0.05).The adverse reaction rates of group A and B were 15.63%(5/32)and 22.22%(10/45),respectively(P>0.05).Conclusion Compared with low dose(0.5 g/d)of metformin,high dose(0.75 g/d)of metformin combined with risperidone has better effects on weight control and glucolipid metabolism in patients with schizophrenia,with certain safety and better efficacy.
10.Optimized lipid nanoparticles enable effective CRISPR/Cas9-mediated gene editing in dendritic cells for enhanced immunotherapy.
Kuirong MAO ; Huizhu TAN ; Xiuxiu CONG ; Ji LIU ; Yanbao XIN ; Jialiang WANG ; Meng GUAN ; Jiaxuan LI ; Ge ZHU ; Xiandi MENG ; Guojiao LIN ; Haorui WANG ; Jing HAN ; Ming WANG ; Yong-Guang YANG ; Tianmeng SUN
Acta Pharmaceutica Sinica B 2025;15(1):642-656
Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLANmCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

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