BACKGROUND:It has been shown that Gushukang affects bone metabolism by regulating nucleotide and amino acid metabolism and immune mechanisms.Current research on the mechanism of Gushukang in the treatment of osteoporosis primarily focuses on osteoblast regulation and requires further improvement from the perspective of osteoclasts. OBJECTIVE:To investigate the mechanism by which Gushukang interferes with osteoclasts in the treatment of osteoporosis using RAW264.7 cells as the research model. METHODS:Twenty-four 8-week-old female Sprague-Dawley rats were randomly divided into four groups(n=6 per group):the three experimental groups were given 1,2 and 4 g/kg osteoporosis solution by gavage(2 times per day),and the control group was given an equal amount of distilled water by gavage(2 times per day).After 7 days of intragastric administration,aortic blood samples were extracted to collect serum samples using centrifugation,and serum samples from the same groups were combined to obtain the low-,medium-,and high-concentration Gushukang-containing and normal sera for the subsequent experiments.(1)RAW264.7 cells were cultured in six groups:normal serum was added to the control group;low,medium,and high concentration groups were added with low,medium,and high concentrations of Gushukang-containing serum,respectively;ML385,a nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor was given in the Nrf2 inhibitor group;and t-BHQ,a Nrf2 activator,was added in the Nrf2 activator group.Cell viability was detected using the cell counting kit-8 assay.(2)The 3rd generation RAW 264.7 cells were cultured and divided into five groups:the blank control group was added with normal serum,the osteoclast group was added with receptor activator of nuclear factor κB ligand(RANKL),and the low-,medium-,and high-concentration groups were added with low-,medium-,and high-concentration Gushukang-containing serum based on the addition of RANKL.Tartrate-resistant acid phosphate staining was performed after 5 days of culture.(3)RAW264.7 cells were cultured and divided into five groups:blank control group was cultured with normal serum,osteoclast group cultured with normal serum and RANKL,high concentration+osteoclast group cultured with RANKL+high concentration Gushukang-containing serum,osteoclast+Nrf2 agonist group cultured with RANKL+t-BHQ,and high concentration+osteoclast+Nrf2 inhibitor group cultured with RANKL+high concentration Gushukang-containing serum+ML385.Western blot assay and determination of reactive oxygen content were performed after 5 days of culture. RESULTS AND CONCLUSION:The cell counting kit-8 results indicated that Gushukang-containing serum,NRF2 inhibitor or agonist had no significant effect on RAW264.7 cell viability.Tartrate-resistant acid phosphate staining results demonstrated that Gushukang-containing serum exhibited a concentration-dependent inhibitory effect on osteoclast differentiation.Western blot analysis and determination of reactive oxygen species revealed that compared with the blank control group,Nrf2 protein expression was decreased in the osteoclast group(P<0.05),while c-Fos and NFATc1 protein expression and reactive oxygen species content were elevated(P<0.05);compared with the osteoclast group,Nrf2 protein expression was elevated and reactive oxygen species content was decreased in the high-concentration+osteoclast group,osteoclast+Nrf2 agonist group,and high-concentration+osteoclast+Nrf2 inhibitor group(P<0.05),while c-Fos and NFATc1 protein expression was decreased in the high concentration+osteoclast group and osteoclast+Nrf2 agonist group(P<0.05);compared with the high concentration+osteoclast group,Nrf2 protein expression was decreased(P<0.05)and reactive oxygen species content was elevated(P<0.05)in the high concentration+osteoclast+Nrf2 inhibitor group.To conclude,Gushukang reduces reactive oxygen species production by activating Nrf2,thereby inhibiting downstream of the c-Fos/NFATc1 pathway and suppressing osteoclast differentiation.

【Objective】 To identify the risk factors of patients of bone metastatic prostate cancer with high tumor load progressed to castration resistant prostate cancer (CRPC), establish a nomogram prediction model and evaluate its consistency and accuracy. 【Methods】 A total of 164 patients diagnosed by puncture and imaging during 2012 and 2022 were included.The general characteristics were analyzed with IBM SPSS software; the variables were screened with Cox regression; the multivariate risk factors with P<0.05 were included in the nomogram prediction model.The consistency and prediction accuracy of the model were evaluated with C-index, receiver operating characteristic (ROC) curve and calibration chart. 【Results】 In univariate analysis, initial prostate-specific antigen (PSA), prostate-specific antigen density (PSAD), Gleason score, T stage, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were correlated with CRPC (P<0.05).Multivariate analysis showed that initial PSA, Gleason score, T stage, ALP and LDH were independent risk factors of CRPC (P<0.05).Based on the above five risk factors, a nomogram prediction model was constructed.The C-index was 0.801, the area under ROC curve (AUC) of 1-year progression-free survival (PFS) was 0.701 (0.608-0.794), and the AUC of 2-year PFS was 0.857 (0.767-0.947).The calibration chart showed that the prediction probability of the model was in good agreement with the actual probability. 【Conclusion】 Initial PSA, Gleason score, T stage, ALP and LDH are independent risk factors of CRPC.The predictive model may be an effective tool for the initial diagnosis of high tumor load bone metastatic prostate cancer, but more data are needed for internal and external validation.

"Tendon Constraining Bone"is an essential theory in osteology and traumatology of traditional Chinese medicine,originating from the statement in Suwen(Plain Questions)that"convergent tendon controlling bones and joints".Since the Yuan and Ming dynasties,the theory of"Tendon Constraining Bone"was formed based on the understanding of anatomical relationships and the need for pathogenesis interpretation,developed by medical practitioners such as ZHU Danxi and ZHANG Jie.The"Tendon Constraining Bone"theory summarizes the physiological connections between tendons and bones and between tendons and zang-fu organs and meridians.Tendons and bones are structurally connected and functionally related,reflected in sturdy bones and tough tendons,upright bones and soft tendons with smoothly-flowing qi and blood,all tendons being related to joints,and thews being related to bones.Tendons and bones are related by meridians and zang-fu organs,specifically reflected in the Yangming channel governing the nourishment of tendons,liver governing tendons,kidneys governing bones,Taiyang channel governing tendons,and Shaoyang channel governing bones.The abnormality of"Tendon Constraining Bone"is the general pathogenesis of various tendon and bone diseases,and it can be caused by changes in the tendon and bone structure,nourishment deficiency,or the pathogenic qi retention.The pathological manifestations of abnormal"Tendon Constraining Bone"are manifested in form and state.Abnormalities in form can manifest as tendon rupture,bone fractures,tendon dislocation,and bone dislocation,whereas abnormalities in state can manifest as tendon urgency,bone pain,tendon laxity,and bone softness.The"Tendon Constraining Bone"theory has influenced the development of treatment principles such as combining motion and quiescence,paying equal attention to bone and flesh,and combining internal and external treatment.This theory has guided the application of basic treatment method such as connecting and rectifying tendons and bones,smoothing tendons and relieving bones,and nourishing tendons and strengthening bones.Therefore,the"Tendon Constraining Bone"theory can significantly guide tendon and bone disease diagnosis and treatment.

Objective:To analyze the clinicopathological features,prognostic value and surgical treat-ment experience in patients with adrenocortical carcinoma with venous tumor thrombus.Methods:We collected relevant data of the patients with adrenocortical carcinoma who had undergone surgery in Peking University Third Hospital from 2018 to 2023.The patients were divided into venous tumor thrombus group and non-tumor thrombus group.The Wilcoxon rank sum test was used to compare the quantitative varia-bles.The chi-squared test and Fisher's exact test were used to compare the categorical variables.The Kaplan-Meier method was used to estimate the survival rate.Results:A total of 27 patients with adreno-cortical carcinoma were included,of whom 11 cases(40.7％)had venous tumor thrombus.In the pa-tients with venous tumor thrombus,8 patients were female and 3 were male.The median age was 49(36,58)years.The median body mass index was 26.0(24.1,30.4)kg/m2.Seven patients presented with symptoms at their initial visit.Six patients had a history of hypertension.Elevated levels of cortisol were observed in 2 cases.Three tumors were found on the left side,while 8 were found on the right side.Median tumor diameter was 9.4(6.5,12.5)cm.On the left,there was a case of tumor thrombus limit-ed to the central vein of the left adrenal gland without invasion into the left renal vein,and two cases of tumor thrombus growth extending into the inferior vena cava below the liver.One case of tumor thrombus on the right adrenal central vein did not invade the inferior vena cava.Four cases of tumor thrombus inva-ded the inferior vena cava below the liver and three cases extended to the posterior of the liver.Ten pa-tients were in European Network for the Study of Adrenal Tumors(ENSAT)stage Ⅲ and one was in ENSAT stage Ⅳ.Open surgery was performed in 6 cases,laparoscopic surgery alone in 4 cases and ro-bot-assisted laparoscopic surgery in 1 case.Two patients underwent ipsilateral kidney resection.Median operative time was 332(261,440)min.Median intraoperative bleeding was 900(700,2 200)mL.Median hospital stay was 9(5,10)days.Median survival time for the patients with tumor thrombus was 24.0 months and median time to recurrence was 7.0 months.The median survival and recurrence time of 16 patients without tumor thrombus were not reached.The patients with tumor thrombus had worse 3-year overall survival(OS)rate(40.9％vs.71.4％;Log-rank,P=0.038)and 2-year recurrence-free sur-vival(RFS)(9.1％vs.53.7％;Log-rank,P=0.015)rates compared with the patients with non-tumor thrombus.Conclusion:Patients with adrenocortical carcinoma with venous tumor thrombus have poor prognosis.Different adrenal tumor resections and venous tumor thrombus removal procedures based on different tumor thrombus locations are safe and effective in treating this disease.

Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

In this study, in order to overcome the shortcomings of the current methods used to identify Bifidobacterium animalis, such as long time, complicated operation and low adaptability of experimental environment, specific primer probes were designed based on ERIC-PCR technology to identify and detect B.animalis.Based on the genomic DNA of B.animalis HP-B1124, the ERIC-PCR reaction conditions of B.animalis HP-B1124 were optimized, and the ERIC-PCR fragments were obtained one by one and sequenced.Two pairs of specific primer probes were designed.The accuracy, specificity, limitation and universality of the two pairs of primer probes were evaluated, and the two pairs of specific primer probes were used for testing the products containing B.animalis in the commercially published formula.The two pairs of specific primer probes designed in this study could be used for identified strains of B.animalis more simply, quickly and targeted.This method has optimized the current relatively traditional methods of pure culture and plate counting identification of B.animalis, and has solved the high requirements of SNP genotyping technology and real-time fluorescence quantitative PCR method for experimental equipment and reagents in the identification of B.animalis to a certain extent.It has the characteristics of low cost, high specificity and earn a broad market development prospect.

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy* ; Leukemia, Promyelocytic, Acute/therapy* ; Prognosis ; Myelodysplastic Syndromes/drug therapy* ; Neoplasms, Second Primary/drug therapy* ; Remission Induction ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective:To explore the potential mechanism of Jiajian Xuezheng Decotion in infiltrative gastric cancer by network pharmacology and proteomics.Methods:The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database was used to find the compounds and their targets of Jiajianxuezhengtang, and the targets of invasive gastric cancer were determined by high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). The predicted target gene of Jiajian Xuezheng Decotion and the target protein data of infiltrative gastric cancer were analyzed by Venny to obtain the target gene. The target gene set was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment by the David. The protein interaction network diagram (PPI) was obtained by the String method, displaying the prescription-drug-compound-gene network in Cytoscape software.Results:69 active ingredients and 215 drug targets were screened from Jiajian Xuezheng Decotion; 660 proteins were significantly up-expressed in infiltrative gastric cancer, and 10 drug targets and gene targets were the common targets. There were 10 protein nodes in the PPI network, of which 3 core nodes were CASP3, BCL2L1 and STAT1. The 11 KEGG pathways were significantly enriched such as include PI3K-Akt signaling pathway, p53 signaling pathway, proteoglycan in cancer, apoptosis, Jak-STAT signaling pathway and other pathways.Conclusions:Jiajian Xuezheng Decotion plays an anti-infiltrative gastric cancer effect possibly regulated apoptosis through PI3K-Akt signaling pathway, p53 signaling pathway and Jak-STAT signaling pathway. This study provides a theoretical basis for further research on the mechanism of Jiajian Xuezheng Decotion in the treatment of invasive gastric cancer.

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.

BACKGROUND: Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS). METHODS: A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score. RESULTS: A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P < 0.05). In addition, a basic model including Gleason score, SM, and SVI was developed and used as a control to assess the incremental predictive power of the new model. The concordance index of our model was slightly higher than CAPRA-S model (0.76 vs. 0.70, P = 0.02) and it was significantly higher than that of the basic model (0.76 vs. 0.66, P = 0.001). Time-dependent ROC curve and decision curve analyses also demonstrated the advantages of the new nomogram. CONCLUSIONS PSA nadir after RP and MTD based on MRI before surgery are independent predictors of BCR. By incorporating PSA nadir and MTD into the conventional predictive model, our newly developed nomogram significantly improved the accuracy in predicting BCRFS after RP.
Humans ; Male ; Neoplasm Grading ; Neoplasm Recurrence, Local/surgery* ; Nomograms ; Prognosis ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms/surgery* ; Retrospective Studies ; Seminal Vesicles