ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective Under the theory guidance of the Fuxingjue and the Tang-Ye-Jing-Fa map,this study aims to explore the common patterns and unique characteristics of five-flavor combinations in formulas for treating different syndromes of cough.Methods Chinese herbal formulas for cough treatment were collected from traditional Chinese medicine(TCM)clinical practice guidelines,consensuses,and textbooks,and their flavor combinations and distribution were clarified.Based on the theory of the Tang-Ye-Jing-Fa map regarding the five flavors for lung diseases(sour for tonifying,salty for purging,and pungent for transforming),the dominant flavors in each formula were statistically analyzed.Further classification was conducted according to the cold-heat properties and the amount of phlegm,and the characteristics and five-flavor combination patterns of formulas for different syndromes were analyzed.Results A total of 21 formulas for treating different syndromes of cough were statistically analyzed,among which 85.7%of the formulas had dominant flavors of"sour,salty,and pungent".For hot cough(9 formulas),sour was mainly used to tonify the lung and bitter to purge the heart(e.g.,Sangxing Tang and Qingjin Huatan Tang);for cold cough(4 formulas),pungent was mainly used to tonify the liver and warm yang(e.g.,San'ao Tang combined with Zhike San and Xiaoqinglong Tang);for cough with abundant phlegm(7 formulas),the focus was on using pungent to purge the spleen and eliminate dampness(e.g.,Erchen Tang combined with Sanzi Yangqin Tang);for cough with little or no phlegm(6 formulas),sour was used as the core to tonify the lung and nourish yin(e.g.,Sha Shen Mai Dong Tang).Conclusion From the perspective of the Tang-Ye-Jing-Fa map,the flavors of"sour,salty,and pungent"play an important role in the composition of formulas for treating cough.Although the five-flavor combinations of formulas for different syndromes of cough vary,they share common characteristics when classified according to cold-heat properties and phlegm amount.These findings provide a theoretical basis for optimizing the combination of Chinese herbal formulas for cough treatment by adjusting the proportion of the five flavors in clinical practice.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective To evaluate the effectiveness of different tip positions applied to midline catheters(MC)and provide evidence-based evidence for venous catheter tip positioning in clinical practice.Methods Computerized searches of PubMed,Web of Science,Embase,Cochrane Library,CINAHL,CNKI,Wanfang Database,VIP,and CBM for studies on the effectiveness of applying MC with different tip positions were performed from the time of database construction to July 2024.Meta-analysis was performed using Rev Man 5.3 software after 2 investigators independently screened the studies,extracted the information and evaluated the quality of the included studies.Results A total of 9 studies with 2 302 hospitalized patients were included.The quality evaluation results of the included studies are all B-level.Meta-analysis showed that when the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the rate of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,and catheter-associated thrombosis were lower,with a statistically significant difference(P＜0.05).When the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the catheter retention time was longer,with a statistically significant difference(P=0.007).The descriptive analysis showed a lower rate of extubation due to complications when the tip of the MC was located in the subclavian vein compared with when the tip was located in the axillary vein(P＜0.05).Conclusion When the tip of the MC is located in the subclavian vein compared to when it is located in the axillary vein,the incidence of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,catheter-associated thrombosis,and the rate of catheter extractions due to complications were lower,and the catheter was left in place for a longer period of time.Due to the limitations of the quantity and quality of the included studies,more large-sample,high-quality studies are needed to further validate the effectiveness of different tip positions of MC.

Aim To investigate the effect of synthetic small interfering RNA(siRNA)targetingβ-arrestin2 on the apoptosis of hepatic stellate cells(HSC)in vitro.Methods The protective effect of scutellarin on high-fat diet and vitamin D3-induced AS rats.Forty male SD rats weighing 180～220 g were randomly divided into the normal group,the high-fat diet group and the low and high-dose scutellarin.A week of adaptive feeding later,the normal group ate normal diet,the oth-er groups ate a high-fat diet and intraperitoneal injec-tion of vitamin D3,while the administration group was intraperitoneally injected with different doses of scutel-larin daily.The animals were anesthetized after 12 weeks,and the rat aortic blood and aortic blood vessels were taken out.Rat aortic blood vessels were stained with hematoxylin-eosin(HE)to observe the pathologi-cal changes.Tissue superoxide dismutase(SOD),ma-londialdehyde(MDA),glutathione peroxidase(GSH-Px)and glutathione-sulfase(GSH-ST)and total cho-lesterol(TC)),the content of triglyceride(TG),low density lipoprotein(LDL-C),high density lipoprotein(HDL-C)were detected.The mRNA expression of PERK and eIF2α in tissues was detected by qRT-PCR.The expressions of GRP78,p-PERK,PERK,p-eIF2α,eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,caspase-3 and caspase-12 were detected by Western blot.Re-sults The results of HE staining showed that the foam cells and lipid deposition under the intima of the scute-llarin group were reduced,which proved that scutellarin had a certain protective effect on vascular endothelial cells.In vivo the expression of TC,TG and LDL-C in scutellarin group decreased and the expression of HDL-C increased.Scutellarin could down-regulate the pro-tein expression of PERK and eIF2α,and down-regulate the expression of GRP78,p-PERK,p-eIF2α,ATF4,CHOP,PUMA,caspase-3,caspase-12 and up-regulated Nrf2 and Bcl-2.The anti-AS effect of scutellarin was proved to be closely related to its regulation of PERK-Nrf2/ATF4-CHOP signaling pathway.Conclusion Scutellarin inhibits endoplasmic reticulum stress and apoptosis by regulating the PERK-Nrf2/ATF4-CHOP signaling pathway,thereby treating AS.

Objective To compare the difference,agreement,and axial length measurement success rate between biometers ZW-30 and IOLMaser 700 based on swept-source optical coherence tomography for the measurement of ocular bi-ological parameters in patients with cataracts.Methods A total of 126 cataract patients(233 eyes)who were advised to undergo cataract surgery at the Department of Ophthalmology at Beijing Tongren Hospital,Capital Medical University from January to February 2024 were included in this study.Two biometers were used to measure the axial length(AL),mean keratometry(Km),anterior chamber depth(ACD),lens thickness(LT),central corneal thickness(CCT),and horizontal corneal diameter[namely,the white-to-white(WTW)distance].The axial measurement success rate of the two biometers and the difference and agreement between the parameters were calculated.Results The mean difference between ZW-30 and IOLMaster 700 was(-0.006±0.042)mm for AL,(-0.074±0.204)D for Km,(0.031±0.051)mm for ACD,(0.001±0.005)mm for CCT,and(-0.286±0.337)mm for WTW,and the differences were statistically significant(all P＜0.05).The mean difference between ZW-30 and IOLMaster 700 was(0.008±0.215)mm for LT,and the difference was not statis-tically significant(t=0.579,P=0.563).The 95％limits of agreement range was between-0.011 mm and 0.000 mm for AL,between-0.474 D and 0.326 D for Km,between-0.010 mm and 0.012 mm for CCT,between-0.068 mm and 0.131 mm for ACD,between-0.116 mm and 0.159 mm for LT,and between-0.947 mm and 0.376 mm for WTW.The intra-class correlation coefficient of all measurements ranged from 0.790 to 1.000.The AL measurement success rate of IOLMaster 700 and ZW-30 was 95.3％and 95.7％,respectively.The latter had an AL measurement success rate of 98.7％after manually marking the position of the retinal identification line.Conclusion There were statistically significant differences between ZW-30 and IOLMaster 700 in the measurement of the AL,Km,ACD,and CCT,which,however,were not clinically significant.The agreement between both was good.ZW-30 had a higher AL measurement success rate,espe-cially for the manual identification function of eyes with opacified refractive media,which can further improve the AL meas-urement success rate and provide reference for clinical work.

Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To analyze the biological parameters of the anterior segment of age-related cataracts patients with or without zonular weakness with the new generation of sweep-source anterior optical coherence tomography (OCT) device CASIA2 to provide a basis for the diagnosis of zonular weakness.Methods:A case-control study was conducted.A total of 158 cases (186 eyes) of patients with age-related cataracts having zonular weakness as a zonular weakness group, and 80 cases (80 eyes) of cataract with age-related cataracts without zonular weakness as a normal zonule group were enroll from June 2022 to June 2023 at Beijing Tongren Hospital.All patients underwent routine preoperative ophthalmological examination including slit lamp microsopy, IOLMaster 700, ocular B-ultrasound and OCT.The anterior chamber depth (ACD), anterior chamber volume (ACV), lens thickness (LT), lens vault (LV), anterior chamber angle opening distance at 750 μm (AOD750), lens decentration and tilt, radius of curvature of the anterior lens surface (RAL), and radius of curvature of the posterior lens surface (RPL) of patients were measured with CASIA2 and compared between the two groups.The relationship between zonular weakness and anterior chamber parameters and lens parameters was evaluated by logistic regression analysis.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital (No.TRECKY2018-049), and all enrolled patients signed the informed consent form.Results:In the zonular weakness group, ACD, ACV, RAL, and AOD750 were (2.34±0.56)mm, (85.05±40.19)mm 3, 7.52 (7.13, 8.08)mm, and 0.27 (0.07, 0.30)mm, respectively, which were smaller than (3.13±0.38)mm, (127.75±38.15)mm 3, 9.28(8.51, 9.76)mm, and 0.52 (0.31, 0.65)mm in the normal zonule group, with statistically significant differences (all P<0.05).LT and LV in the zonular weakness group were (5.14±0.45)mm and (1.22±0.53)mm, respectively, which were larger than (4.27±0.52)mm and (0.32±0.30)mm in the normal zonule group, and the differences were statistically significant (both P<0.05).Magnitude of lens decentration and tilt in the zonular weakness were 0.34 (0.13, 0.45)mm and 6.44 (3.67, 7.32)°, respectively, which were significantly larger than 0.19 (0.12, 0.25)mm and 4.88 (3.85, 5.65)° in the normal zonule group (both P<0.05).No obvious pattern was found in the direction of decentration and tilt.Logistic regression analysis showed that LV and lens decentration were risk factors of zonular weakness (odds ratios [ OR]=706.170, 335.339; both P<0.05), and RAL was a protective factor of zonular weakness ( OR=0.239, P<0.05). Conclusions:Age-related cataract patients with zonular weakness often present with a decrease in ACV due to increased anterior convexity of the lens.Decreased RAL, increased lens decentration and elevated LV are risk factors for zonular weakness.

BACKGROUND:Dental follicle cells are widely used in periodontal tissue regeneration engineering because of their excellent characteristics.With the development of biological scaffold materials,their relationship with periodontal tissue regeneration technology is increasingly close.OBJECTIVE:To review the performance of ivory follicle cells under the influence of internal and external biological factors by different experiments,and analyze their effects on the biological characteristics of dental follicle cells with scaffold materials.METHODS:Using"dental follicle cell,scaffolds,material,periodontal tissue regeneration,tissue engineering,review"as English and Chinese key words,the articles published in PubMed,Sciencedirect,and CNKI from 2013 to 2023 were searched,and finally 95 articles were included for analysis and discussion.RESULTS AND CONCLUSION:(1)Dental follicle cells originate from dental follicle tissue,which has certain stem cell differentiation potential.Because of its excellent performance,it is actively used in periodontal tissue regeneration engineering research.(2)The proliferation and osteogenic differentiation of dental follicle cells are affected by many biological factors,and both endogenous and exogenous factors can promote the proliferation and osteogenic differentiation of dental follicle cells to a certain extent.(3)3D printing technology and nanotechnology enable researchers to manufacture more suitable scaffold materials.(4)Polymer materials show us their flexibility and plasticity in periodontal tissue regeneration.We can manufacture targeted scaffold materials according to different defect sites to achieve efficient tissue regeneration.The good biocompatibility of inorganic materials makes them widely used in periodontal tissue regeneration engineering.By adjusting the content of nanoscale inorganic materials or improving the performance of scaffolds,scaffolds with better biocompatibility can be prepared.(5)There are many new synthetic(composite)materials,which show us excellent characteristics.However,because the mechanism of biological factors in scaffold materials on dental follicle cells is complicated,and the research on dental follicle cells is mostly concentrated on in vitro culture,so how to make scaffold materials more suitable for the growth and development of dental follicle cells and apply them safely and effectively in clinical treatment is the future research direction.