Objective By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Dalbergia rimosa Roxb. by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as UV, IR, MS, 1D/2D NMR and by comparison with literature information as dalbergiquinol A (1), dalbergiquinol B (2), R-(-)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol (3), neokhriol A (4), mucronulatol (5), (3R)-7,2′,3′-trihydroxy-4′-methoxy-isoflavane (6), isomucronulatol (7), (3S)-violanone (8), 3′-O-methylviolanone (9), eryvarin M (10), (±)-α,3,4,2′,4′-pentahydroxydihydrochalcone (11) and (-)-butin (12). Compound 1 and 2 are new compounds, and compounds 3-12 were isolated from this plant for the first time. Compounds 1, 2, 4, 6, 8, 11, 12 showed good scavenging effect on DPPH free radical.

BACKGROUND:Previous studies have shown that human dental pulp stem cells have good osteogenic differentiation potential and are potential seed cells in bone tissue engineering,and the effect of recombinant human growth hormone on the proliferative osteogenic differentiation of human dental pulp stem cells is still unclear. OBJECTIVE:To explore the effect of recombinant human growth hormone on the proliferation and osteogenic differentiation of human dental pulp stem cells. METHODS:Human dental pulp stem cells were isolated and cultured by tissue block culture method.After screening according to the drug concentration gradient,recombinant human growth hormone containing 10,100,250,500,1 000 μg/L was selected as the experimental group,and 0 μg/L without recombinant human growth hormone was selected as the control group.CCK-8 detection reagents were used on days 1,3,5,and 7 after the drug intervention to detect the proliferation of human dental pulp stem cells.Different concentrations(10,100,250,500,and 1 000 μg/L)of recombinant human growth hormone were added to the osteogenesis induction solution to intervene in human dental pulp stem cells.Alkaline phosphatase activity was detected by alkaline phosphatase staining and semi-quantitative analysis on day 7 of mineralization induction.The mRNA expression levels of osteogenic gene type I collagen,osteocalcin and Runt-related transcription factor 2 were detected by fluorescence quantitative RT-qPCR.Alizarin red staining was performed on day 14 of mineralization induction to detect osteogenic mineralized nodules. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that from the third day of intervention,the 100,250,500,1 000 μg/L recombinant human growth hormone group could promote the proliferation of human dental pulp stem cells compared with the control group(P<0.01).(2)The alkaline phosphatase activity of human dental pulp stem cells in the 100,250,and 500 μg/L recombinant human growth hormone group was significantly increased compared with the control group(P<0.01).The number of alizarin-stained mineralized nodules in human dental pulp stem cells in the 100,250 μg/L recombinant human growth hormone group was significantly increased compared with the control group(P<0.01).Compared with the control group,the mRNA expression of type I collagen and osteocalcin increased in the 250 μg/L recombinant human growth hormone group(P<0.05,P<0.01).mRNA expression of Runt-associated transcription factor 2 increased in the 100 and 250 μg/L recombinant human growth hormone groups(P<0.01).(3)According to the above results,recombinant human growth hormone at a concentration of 250 μg/L is a more suitable concentration to promote the proliferation and osteogenic differentiation of human dental pulp stem cells.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To explore the clinical and electrophysiological characteristics of peripheral neuropathy in prediabetic patients.Methods:Subjects aged 20-65 years with high-risk factors of impaired glycemia enrolled in Beijing Tiantan Hospital, Capital Medical University from 2019 to 2022 were recruited to conduct oral glucose tolerance test, after excluding other causes of neuropathy or radiculopathy. Patients with impaired fasting glucose or impaired glucose tolerance were defined by American Diabetes Association criteria. These patients were divided into clinical polyneuropathy (PN) and clinical non-PN groups, according to the 2010 Toronto consensus criteria and the presence of PN symptoms and signs or not. Nerve conduction studies (NCS), F wave, sympathetic skin response (SSR), R-R interval variation (RRIV) and current perception thresholds (CPT) were performed and the abnormal rate was compared between different electrodiagnostic methods and between clinical subgroups.Results:Among the 73 prediabetic patients ultimately enrolled, only 20 (27.4%) can be diagnosed as clinical PN according to the Toronto consensus criteria. The abnormal rate of CPT (68.5%, 50/73) was significantly higher than those of F wave (2.7%, 2/73), lower limb NCS (0, 0/73), upper limb NCS changes of carpal tunnel syndrome (26.0%, 19/73), SSR (6.8%, 5/73) and RRIV (5.5%, 4/73; McNemar test, all P<0.001). With sinusoid-waveform current stimuli at frequencies of 2 000 Hz, 250 Hz and 5 Hz, the CPT device was used to measure cutaneous sensory thresholds of large myelinated, small myelinated and small unmyelinated sensory fibers respectively. CPT revealed a 21.9% (16/73) abnormal rate of unmyelinated C fiber in the hands of prediabetic patients, significantly higher than that of large myelinated Aβ fibers [8.2% (6/73), χ2=5.352, P=0.021]. Both abnormal rates of small myelinated Aδ [42.5% (31/73)] and unmyelinated C fibers [39.7% (29/73)] in the feet of prediabetic patients were significantly higher than that of large myelinated Aβ fibers [11.0% (8/73), χ2=18.508, 15.965, both P<0.001]. Compared with the clinical non-PN group, the abnormal rates of CPT [90.0% (18/20) vs 60.4% (32/53), χ2=5.904, P=0.015] and SSR [20.0% (4/20) vs 1.9% (1/53), P=0.016) were significantly higher in the clinical PN group. Conclusions:Peripheral neuropathies in prediabetic patients are usually asymptomatic or subclinical, and predispose to affect unmyelinated and small myelinated sensory fibers. Selective electrodiagnostic measurements of small fibers help to detect prediabetic neuropathies in the earliest stages of the disease.

Objective To explore the value of controlling nutritional status(CONUT)score and related inflammatory indicators in predicting the prognosis of clear cell renal cell carcinoma(ccRCC)patients,to provide a reference for better clinical assessment and individualized treatment plan.Methods A retrospective study was conducted on 132 patients with ccRCC admitted to four comprehensive hospitals in Yibin during 2010 and 2018.Patients'medical and follow-up records were collected,and receiver operating characteristic(ROC)curve was drawn to analyze the area under the curve(AUC)and optimal cut-off value of CONUT score and related indicators.Survival curve was plotted with Kaplan-Meier method,and the influencing factors of prognosis were analyzed with Log-rank test and Cox regression.Results During the follow-up of 62(53,71)months,37(28.03％)deaths occurred.The disease-specific survival(DSS)and progression-free survival(PFS)were 51(41,58)and 46(35,56)months,respectively.The 3-year and 5-year DSS and PFS were 84.09％and 71.97％,and 75.00％and 71.97％,respectively.The AUC of CONUT score,neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and lymphocyte to monocyte ratio(LMR)were 0.980,0.905,0.899 and 0.884,respectively,with the optimal cut-off values of 3.50,3.19,89.07 and 3.56,respectively.Cox regression showed that CONUT score(HR=0.042,95％CI:0.013-0.140)and PLR(HR=0.182,95％CI:0.045-0.744)were associated with DSS;CONUT score(HR=0.029,95％CI:0.010-0.086)and LMR(HR=2.984,95％CI:1.227-7.258)were associated with PFS.Conclusion The prognosis of ccRCC patients is related to their nutritional,immune,and inflammatory status.CONUT score and inflammatory factors(PLR,LMR)may be important predictors of DSS and PFS.

Studies on chemical constituents in the rhizome of Dalbergia rimosa Roxb. The chemical constituents from the ethyl acetate part of D. rimosa were isolated and purified by silica gel, MCI gel, Sephadex LH-20 gel and semi-preparative HPLC, and the stuctures were identified by spectral method. Thirteen compounds were isolated from the ethyl acetate part of the rhizome of D. rimosa and identified as dalbergiaisoflavones A, B (1, 2), formononetin (3), 7,4′-dimethoxyisoflavone (4), 4′,6,7-trimethoxyisoflavone (5), biochanin A (6), prunetin (7), 7-O-methyltectorigenin (8), 3′-hydroxydaidzein (9), orobol 7,3′-dimethyl ether (10), 2′,7-dihydroxy-4′,5′- dimethoxyisoflavone (11), pruinosanone E (12), caviunin (13). Compounds 1 and 2 are new compounds, and compounds 3-13 were isolated from this plant for the first time. Compounds 9 and 11 had remarkable scavenging effect on DPPH free radicals.

Objective:To analyze the clinical characteristics and prognosis of patients with CD5+diffuse large B-cell lymphoma(DLBCL).Methods:The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed.According to CD5 expression,the patients were divided into CD5+group and CD5-group.The clinical characteristics and prognosis of the two groups were statistically analyzed.Results:The median age of patients in CD5+group was 62 years,which was higher than 56 years in CD5-group(P=0.048).The proportion of women in CD5+group was 62.96％,which was significantly higher than 41.79％in CD5-group(P=0.043).The proportion of patients with IPI score＞2 in CD5+group was 62.96％,which was higher than 40.30％in CD5-group(P=0.031).Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+group were 27(3-77)and 31(3-76)months,respectively,which were both shorter than 30(5-84)and 32.5(4-83)months in CD5-group(P=0.047,P=0.026).Univariate analysis showed that advanced age,positive CD5 expression,triple or double hit at initial diagnosis,high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients.Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age.Conclusion:CD5+DLBCL patients have a worse prognosis than CD5-DLBCL patients.Such patients are more common in females,with advanced age and high IPI score,which is a special subtype of DLBCL.

Objective:To investigate the cause of the production of anti-D and anti-E mixed antibody in an RhD positive patient.Methods:The ABO/Rh blood group typing and irregular antibody specificity were identified by conventional serological methods,the RHD gene exon 1-10 and heterozygous analysis were performed by sequence-specific primer polymerase chain reaction (PCR-SSP),and the whole exon sequence was analyzed by first-generation sequencing.Results:The patient's Rh blood group was weak D Type33,with the allele was RHD*01W.33,the patients was found to be RhD+/RHD-heterozygous,with an Rh typing of Ccee,and the patient had developed anti-D combined with anti-E mixed antibodies.Conclusion:The patient has A c.520G>A mutation in exon 4 of the RHD gene,to lead decreased expression of RhD antigen in red blood cells and the anti-D and anti-E mixed antibodies were produced by transfusion immunostimulation.