BACKGROUND:Chondrocyte apoptosis is an important factor in the development of osteoarthritis,and Complanatoside A has a flavonoid effect,which can inhibit apoptosis of various cells,but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE:To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS:(1)The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected,and chondrocytes were isolated,cultured in vitro,and identified.(2)Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0-160 μmol/L.(3)Chondrocytes were divided into blank group,sodium nitroprusside(1.5 mmol/L)-induced group,and sodium nitroprusside(1.5 mmol/L)+Complanatoside A(5 μmol/L)group.The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry.The expression of type Ⅱ collagen and SOX9 was detected by immunofluorescence staining.The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION:The cells extracted in vitro were cultured and stained,and were clearly identified as chondrocytes.Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L,and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L,especially when the concentration was 5 μmol/L.The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group,while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group.The fluorescence intensity of type Ⅱ collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group,while the fluorescence intensity of type Ⅱ collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group.In the sodium nitroprusside-induced group,the protein expression of Bax,Caspase-3,matrix metalloproteinase 13,Wnt3a,Wnt5a and β-catenin was higher than that of the blank control group,while the protein expression of Bcl-2 was lower than that of the blank control group.In the sodium nitroprusside+Complanatoside A group,except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group,the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group.To conclude,Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis,which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors,and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway.

AIM: To investigate the impact of corneal fluorescein sodium(NaF)staining on the examination results of iTrace visual function analyzer(iTrace).METHODS: Prospective cohort study. Totally 100 patients(100 eyes)with ametropia who visited the outpatient department of Anhui Eye Hospital from April to November 2024 were recruited. They were divided into an experimental group and a control group, with 50 patients(50 eyes, and only the right eyes were selected for inclusion)in each group. In the experimental group, corneal staining was performed using fluorescein sodium staining test strips, while in the control group, 1 drop of 0.9% normal saline was instilled into the eyes. The iTrace examination was conducted before the intervention and at 5, 10, and 20 min after the intervention. The total corneal higher-order aberrations, spherical aberration, coma aberration, trefoil aberration, best sphere value(RO value), asphericity factor(Q value), and corneal vertical refractive power difference(IS value)at each time of examination were recorded and compared.RESULTS: There was no statistically significant difference in the baseline levels between the two groups(all P>0.05). Intra-group comparison revealed that the total higher-order aberrations, spherical aberration, coma aberration, and trefoil aberration measured 5 min after NaF staining in the experimental group were significantly increased compared with those before staining(all P<0.05). Inter-group comparison showed that the changes(differences from the baseline)in the total corneal higher-order aberrations, spherical aberration, coma aberration, and trefoil aberration measured by iTrace 5 min after the intervention in the experimental group were significantly greater than those in the control group(all P<0.05). There was no statistically significant difference in the changes(differences from the baseline)of various iTrace parameters measured at 10 and 20 min after the intervention between the two groups(all P>0.05). There was no statistical significance in the RO value, Q value, and IS value in the two groups(all P>0.05).CONCLUSION: Corneal NaF staining can cause a short-term increase in the wavefront aberration values(total corneal higher-order aberrations, spherical aberration, coma aberration, trefoil aberration)measured by iTrace, and it gradually disappears with the passage of time. However, it has no impact on the measurement of corneal topography parameters(RO value, Q value, IS value).

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Objective:To assess the value of cerebral small vessel disease (CSVD) burden in predicting prognosis in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) after endovascular therapy (EVT).Methods:The study was a cross-sectional study. A total of 242 patients with AIS due to anterior circulation LVO received EVT in the First Affiliated Hospital of Nanjing Medical University from February 2018 to September 2022. The clinical and imaging data of all patients were analyzed retrospectively. On follow-up MRI within 7 days after EVT, CSVD features [white matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed, cerebral atrophy] and CSVD burden score (0-5) was evaluated. Modified Rankin scale (mRS) score at 90 days after EVT was assessed. Patients were categorized into a mild burden group (0-1 points) and a moderate-severe burden group (2-5 points) based on CSVD burden score. Meanwhile, patients were categorized into a good prognosis group (0-2 points) and a bad prognosis group (3-6 points) based on mRS score at 90 days after EVT. Mann-Whitney U test and χ2 test were used to compare the difference of clinical and imaging indexes between the 2 groups, and variables with P<0.1 in the univariate analysis were included in the multifactorial logistic regression to screen for independent factors to predict the prognosis. Results:There were 169 patients in the good prognosis group and 73 patients in the bad prognosis group out of 242 patients. Compared with the good prognosis group, age, incidence of hyperlipidemia, baseline National Institutes of Health Stroke Scale (NIHSS) scores, incidence of hemorrhagic conversion, CSVD burden scores, incidence of periventricular WMH scores of 3 and/or deep WMH scores≥2, and incidence of moderate-severe cerebral atrophy of patients in the bad prognosis group were higher, and the incidence of complete recanalization was lower (all P<0.05). Multivariate analysis showed hyperlipemia ( OR=8.438, 95% CI 1.691-42.119, P=0.009), baseline NIHSS score ( OR=1.103, 95% CI 1.047-1.162, P<0.001), complete recanalization ( OR=0.131, 95% CI 0.038-0.454, P=0.001) and hemorrhage transformation ( OR=1.952, 95% CI 1.031-3.697, P=0.040) were independent factors for the prognosis of EVT in patients with LVO AIS. There were 157 cases in the mild burden group and 85 cases in the moderate-severe burden group. The 90-day mRS score was higher in the moderate-severe burden group compared with the mild burden group ( Z=-2.24, P=0.025). Conclusion:CSVD burden has some clinical implications in predicting the prognosis of EVT in patients with anterior circulation LVO AIS.