BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Objective To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway.Methods NIH-3T3 cells were treated with quercetin or MCC950(a specific inhibitor of NLRP3)before stimulation with lipopolysaccharide(LPS)and ATP to induce cell pyroptosis.The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times.Morphological changes of the treated cells was observed,and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA;the protein expressions of NLRP3,cleaved caspase-1,and GSDMD-N and the mRNA levels of NLRP3,caspase-1 and GSDMD were detected using Western blotting and qRT-PCR.The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay.Results The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results.LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling,cell membrane rupture and leakage of cell contents,significantly increased IL-18 and IL-1β levels,and enhanced protein expressions of NLRP3,cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3,caspase-1 and GSDMD.LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells.Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP,lowered the concentrations of IL-18 and IL-1β,decreased the expression levels of NLRP3,caspase-1/cleaved caspase-1,GSDMD/GSDMD-N,and reduced the number of TUNEL-positive cells and LDH release.Conclusion Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Objective:Ventricular septal defect(VSD)is a prevalent congenital cardiac anomaly.By enhancing the occluder design and optimizing procedural approaches,the indications for VSD closure can be broadened while minimizing associated complications.The utilization of fully biodegradable occluder holds promising potential in resolving conduction block issues encountered during VSD closure.This study aims to compare the results of the fully biodegradable occluder with the metal occluder in transoesophageal echocardiography-guided VSD closure via lower sternal level minor incision at the interim follow-up,and to find risk factors for the occurrence of electrocardiographic and valvular abnormalities postoperatively. Methods:We reviewed the postoperative and 3-year follow-up data of all patients who underwent the randomized controlled study of VSD closure from January 1 to November 7,2019 in the Second Xiangya Hospital of Central South University.The safety and efficacy of the procedure were assessed and compared between the 2 groups by electrocardiogram and echocardiography results,and the risk factors for the occurrence of postoperative electrocardiogram and valve abnormalities were studied with Logistic regression analysis. Results:Twelve and fifteen patients underwent VSD closure with the metallic occluder and the fully biodegradable occluder,respectively.All patients survived during the follow-up period without major complications such as atrioventricular block,significant residual shunt,too rapid absorption of the occluder,and significant valvular regurgitation.There were no significant differences in the results of electrocardiograph and color Doppler ultrasonography the metal occluder group and the fully biodegradable occluder group 1,2,and 3 years after operation(all P>0.05).The size of the occluder were risk factors for tricuspid regurgitation at 2 and 3 years postoperatively,and the difference between the occluder size and the VSD defect size were risk factors for tricuspid regurgitation at 2 years postoperatively(P<0.05). Conclusion:This study adequately demonstrates the safety and efficacy of fully biodegradable occluders in small VSD closure and shows the same postoperative effects as conventional nitinol occluders.

Objective To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway.Methods NIH-3T3 cells were treated with quercetin or MCC950(a specific inhibitor of NLRP3)before stimulation with lipopolysaccharide(LPS)and ATP to induce cell pyroptosis.The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times.Morphological changes of the treated cells was observed,and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA;the protein expressions of NLRP3,cleaved caspase-1,and GSDMD-N and the mRNA levels of NLRP3,caspase-1 and GSDMD were detected using Western blotting and qRT-PCR.The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay.Results The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results.LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling,cell membrane rupture and leakage of cell contents,significantly increased IL-18 and IL-1β levels,and enhanced protein expressions of NLRP3,cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3,caspase-1 and GSDMD.LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells.Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP,lowered the concentrations of IL-18 and IL-1β,decreased the expression levels of NLRP3,caspase-1/cleaved caspase-1,GSDMD/GSDMD-N,and reduced the number of TUNEL-positive cells and LDH release.Conclusion Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Objective To establish an ultra-high liquid chromatography(UPLC)characteristic spectrum of Rheum tanguticum Maxim.ex Balf.water decoction and conduct chemical pattern recognition analysis,and to identify the medicinal materials of different origins and different processed products.Methods:UPLC was adopted to establish the characteristic spectra of 15 batches of Rheum tanguticum Maxim.ex Balf.Cluster analysis combined with principal component analysis was used to analyze their quality.Rhei Radix et Rhizoma from different origins and different processed products of Rheum tanguticum Maxim.ex Balf.were identified.Results:The characteristic spectrum of Rheum tanguticum Maxim.ex Balf.water decoction was established,18 common peaks were identi-fied,and 15 batches of Rheum tanguticum Maxim.ex Balf.were divided into 2 categories according to their origins by cluster analysis.The similarity between 15 batches of samples from different origins and the control spectrum was greater than 0.900.According to OPLS-DA analysis,a total of 6 markers(rhein-8-O-β-D-glu-cosid,resveratrol-4'-O-β-D-(6''-O-D-gallyl)glucopyranside,isolindleyin,rhein,epicatechin-3-O-D-gallate,and catechin)affecting the quality of Rheum tanguticum Maxim.ex Balf.water decoction samples were found.Rhei Radix et Rhizoma from different origins and different processed products of Rheum tanguticum Maxim.ex Balf.can be effectively distinguished.Conclusion:The established characteristic spectrum method is easy to operate and has good repeatability.It can be used for the quality control of Rheum tanguticum Maxim.ex Balf.water decoction,and can provide reference for the formulation of quality standard of formula granules of Rhei Radix et Rhizoma.

Objective To investigate the potential of ginkgolide B(GB)in mitigating vascular endothelial injury by antagonizing endoplasmic reticulum stress(ERS)and elucidate its underlying molecular mechanism.Methods An injury model of human bone marrow-derived endothelial progenitor cells(EPCs)induced by tunica-mycin(TM)was established.Cell proliferation was assessed using MTS assay,while cell viability was determined through Calcein-AM/EthD-I double staining.Transwell assay was employed to evaluate cell migration ability.DCFH-DA staining was utilized to measure intracellular ROS levels,and NADPH activity was quantified via ELISA.JC-1 and DiOC6 staining were performed for qualitative and quantitative assessment of mitochondrial membrane potential respectively.Qrt-pcr analysis was conducted to determine mRNA expression levels,whereas western blot analysis enabled detection of protein expression levels in the cells.Results GB dose-dependently attenuated tunicamycin-induced ERS-mediated endothelial injury in hEPCs,as evidenced by decreased cell viability,impaired cell migration,and angiogenesis inhibition(P<0.01).Furthermore,GB treatment significantly reduced ROS production and NADPH levels within the cells(P<0.01),while also inhibiting ERS-mediated decline in mitochondrial membrane potential concentration-dependently(P<0.01).Additionally,GB inhibited the expression of ERS-related proteins such as GRP78,ATF4,CHOP etc.,regulated apoptosis-related protein Bcl-xl,Bax cleaved caspase-4 cytochrome c;thereby effectively counteracting endoplasmic reticulum stress-induced cellular damage.Conclusions GB exerts a protective effect on vascular endothelium by antagonizing endoplasmic reticulum stress;this mechanism may be attributed to its ability to reduce intracellular reactive oxygen species levels.It also suppresses the expression of ERS-related proteins(CHOP78 and ATF4),and modulates apoptosis-associated proteins(Bcl-xl,Bax,cleaved caspase-4,and cytochrome c).

How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 ^-5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Neoplasm, Residual/pathology* ; Biomarkers, Tumor/genetics* ; Computational Biology

Objective:To investigate the short-term efficacy of totally laparoscopic distal gastrectomy (TLDG) after endoscopic submucosal dissection (ESD) versus direct TLDG for early gastric cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 623 patients with early gastric cancer who were admitted to the First Affiliated Hospital of Nanjing Medical University from March 2014 to December 2019 were collected. There were 405 males and 218 females, aged from 26 to 86 years, with a median age of 62 years. Of 623 patients, 25 cases undergoing TLDG after ESD were divided into ESD+TLDG group and 598 cases undergoing TLDG directly were divided into TLDG group. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups after propensity score matching; (2) intraoperative and postoperative situations of TLDG; (3) stratification analysis of the ESD+TLDG group. The propensity score matching was conducted by 1∶2 matching using the nearest neighbor method. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was done using the t test. Measurement data with skewed distribution were represented as M (range) and comparison between groups was done using the Mann-Whitney U test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was analyzed using the Mann-Whitney U test. Results:(1) The propensity score matching conditions and comparison of general data between the two groups after propensity score matching: 75 of 623 patients had successful matching, including 25 in the ESD+TLDG group and 50 in the TLDG group. Before propensity score matching, the body mass index (BMI), cases with tumor diameter ≤20 mm, 21 to 30 mm or>30 mm, cases with tumor classified as stage Ⅰ, stage Ⅱ or stage Ⅲ of clinical staging were (22.3±3.6)kg/m 2, 16, 6, 3, 24, 1, 0 of the ESD+TLDG group, respectively, versus (24.3±2.7)kg/m 2, 238, 125, 235, 312, 126, 160 of the TLDG group, showing significant differences in the above indicators between the two groups ( t=2.744, Z=?2.834, ?4.209, P<0.05). After propensity score matching, the BMI, cases with tumor diameter ≤20 mm, 21 to 30 mm or >30 mm, cases with tumor classified as stage Ⅰ or stage Ⅱ of clinical staging were (22.3±3.6)kg/m 2, 16, 6, 3, 24, 1 of the ESD+TLDG group, versus (23.6±2.9)kg/m 2, 29, 12, 9, 48, 2 of the TLDG group, showing no significant difference between the two groups ( t=1.542, Z=?0.597, 0.000, P>0.05). (2) Intraoperative and postoperative situations of TLDG: after propensity score matching, the operation time and time to postoperative drainage tube removal were 180 minutes(range, 124 to 289 minutes) and 6 days(range, 4 to 13 days) of the ESD+TLDG group,respectively,versus 170 minutes(range, 106 to 250 minutes) and 6 days (range, 4 to 9 days) of the TLDG group, showing significant differences between the two groups ( Z=-2.396, -3.039, P<0.05). Cases with the volume of intraoperative blood loss <50 mL, 50 to 100 mL or >100 mL, the number of lymph node dissected, duration of postoperative hospital stay, cases with perioperative complications as incision fat liquefaction, delayed gastric emptying, anastomotic bleeding or pulmonary infection were 7, 9, 9,34(range, 16 to 58), 8 days(range, 6 to 31 days), 1, 1, 0, 0 of the ESD+TLDG group,respectively,versus 18, 26, 6, 39 (range, 22 to 68), 8 days (range, 6 to 29 days), 0, 0, 1, 1 of the TLDG group, showing no significant difference between the two groups ( Z=-1.703, -1.958, -1.139, χ2=0.033, P>0.05). Cases with anastomotic bleeding were recovered after hemostasis under endoscopy and cases with other perioperative complications were recovered after conservative treatment. (3) Stratification analysis of the ESD+TLDG group. ① For 5 cases undergoing TLDG ≤14 days after ESD and 20 cases undergoing TLDG >14 days after ESD, the operation time of TLDG, cases with the volume of intraoperative blood loss <50 mL, 50 to 100 mL or >100 mL during TLDG, the number of lymph node dissected, time to postoperative drainage tube removal, duration of postoperative hospital stay, cases with perioperative complications were 200 minutes(range, 170 to 289 minutes), 0, 3, 2, 36(range, 9 to 57), 7 days(range, 5 to 9 days), 8 days(range, 7 to 9 days), 1 and 180 minutes (range, 124 to 253 minutes), 8, 6, 6, 34(range, 8 to 78), 6 days(range, 4 to 13 days), 8 days(range, 6 to 31 days), 1, respectively, showing no significant difference in the operation time of TLDG, volume of intraoperative blood loss during TLDG, the number of lymph node dissected, time to postoperative tube removal and duration of postoperative hospital stay between the two groups ( Z=?1.536, ?1.993, ?0.238, ?0.932, ?0.589, P>0.05), and no significant difference in cases with perioperative complications between the two groups ( P>0.05). ② For 13 cases undergoing TLDG ≤21 days after ESD and cases undergoing TLDG >21 days after ESD, the operation time of TLDG, cases with the volume of intraoperative blood loss as <50 mL, 50 to 100 mL or >100 mL during TLDG, the number of lymph node dissected, time to postoperative drainage tube removal, duration of postoperative hospital stay, cases with perioperative complications were 200 minutes(range, 145 to 289 minutes), 2, 6, 5, 34(range, 8 to 57), 6 days(range, 4 to 11 days), 8 days(range, 6 to 11 days), 1 and 179 minutes(range, 124 to 240 minutes), 6, 3, 3, 34(range, 16 to 78), 6 days(range, 5 to 13 days), 8 days(range, 6 to 31 days), 1, respectively, showing a significant difference in the operation time of TLDG between the two groups ( Z=?2.241, P<0.05), while showing no significant difference in the volume of intraoperative blood loss during TLDG, the number of lymph node dissected, time to postoperative drainage tube removal, duration of postoperative hospital stay between the two groups ( Z=?1.471, ?0.163, ?0.084, ?0.194, P>0.05) and no significant difference in cases with perioperative complications between the two groups ( P>0.05). ③ For 15 cases undergoing TLDG ≤28 days after ESD and 10 cases undergoing TLDG >28 days after ESD, the operation time of TLDG, cases with the volume of intraoperative blood loss <50 mL, 50 to 100 mL or >100 mL during TLDG, the number of lymph node dissected, time to postoperative drainage tube removal, duration of postoperative hospital stay, cases with perioperative complications were 190 minutes (range, 145 to 289 minutes), 2, 7, 6, 33(range, 8 to 57), 6 days(range, 4 to 11 days), 8 days(range, 6 to 31 days), 1 and 179 minutes(range, 124 to 240 minutes), 6, 2, 2, 37(range, 16 to 78), 6 days (range, 5 to 13 days), 8 days(range, 6 to 14 days), 1, respectively, showing no significant difference in the operation time of TLDG, volume of intraoperative blood loss during TLDG, the number of lymph node dissected, time to postoperative tube removal and duration of postoperative hospital stay between the two groups ( Z=?1.619, ?2.000, ?0.667, ?0.370, ?0.057, P>0.05), and no significant difference in cases with perioperative complications between the two groups ( P>0.05). Conclusions:Compared with cases undergoing TLDG directly, the operation time to TLDG and time to drainage tube removal after TLDG for cases undergoing ESD+TLDG are prolonged, but there is no difference in the short-term efficacy. For cases undergoing TLDG ≤21 days after ESD and cases undergoing TLDG >21 days after ESD, there is a significant difference in the operation time of TLDG.

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Animals ; Disease Models, Animal ; Female ; Gene Editing ; Humans ; Lamin Type A/metabolism* ; Macaca fascicularis ; Progeria/pathology*