BACKGROUND:Knee osteoarthritis(KOA)is a common chronic inflammatory disease that causes damage to joint cartilage and surrounding tissues.Immune cells play an important role in the immune-inflammatory response in knee osteoarthritis,but the specific mechanisms involved are still not fully understood. OBJECTIVE:To evaluate the potential causal relationship between 731 immune cell phenotypes and the risk of knee osteoarthritis using Mendelian randomization. METHODS:Summary statistics of genome-wide association studies(GWAS)for 731 immune cell phenotypes(from GCST0001391 to GCST0002121)obtained from the GWAS catalog and GWAS data for knee osteoarthritis from the IEUGWAS database(ebi-a-GCST007090)were used.Inverse variance-weighted method,MR-Egger regression,weighted median method,weighted mode method,and simple mode method were employed to investigate the causal relationship between immune cells and knee osteoarthritis.Sensitivity analyses were conducted to assess the reliability of the Mendelian randomization results.Reverse Mendelian randomization analysis was also performed using the same methods. RESULTS AND CONCLUSION:The forward MR analysis indicated significant causal relationships(FDR<0.20)between knee osteoarthritis and four immune cell phenotypes,namely CD27 on CD24+CD27+in B cells(OR=1.026,P=0.000 26,Pfdr=0.18),CD33 on CD33dim HLA DR-in myeloid cells(OR=1.014,P=0.000 50,Pfdr=0.18),and CD45RA+CD28-CD8br%CD8br in Treg cells(OR=1.001,P=0.000 78,Pfdr=0.18),and PDL-1 on monocytes in mononuclear cells(OR=0.952,P=0.000 98,Pfdr=0.18).These immune cell phenotypes showed direct positive or negative causal associations with the risk of knee osteoarthritis.Reverse Mendelian randomization analysis revealed no significant causal relationships(FDR<0.20)between knee osteoarthritis as exposure and any of the 731 immune cell phenotypes.The results of sensitivity analysis show that the P-values of the Cochran's Q test and the MR-Egger regression method for bidirectional Mendelian randomization were both greater than 0.05,indicating that there is no significant heterogeneity and pleiotropy in the causal effect analysis between immune cell phenotypes and knee osteoarthritis.To conclude,there may be four potential causal relationships between immune cell phenotypes,such as CD27 on CD24+CD27+cells,CD33 on CD33dim HLA DR-cells,CD45RA+CD28-CD8br%CD8br cells,and PDL-1 on monocytes,and knee osteoarthritis.These findings provide valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring early prevention and treatment strategies.They also offer new directions for the development of intervention drugs.

Background: Cervical cancer is a common disease among women. Treatment for cervical cancer includes surgery, radiation therapy, chemotherapy, or a combination of chemotherapy and radiation therapy. Cisplatin is the first-line chemotherapy drug for cervical cancer. Research has shown that about 20% of cervical cancer patients become resistant to chemotherapy, which results in decreased results, tumor recurrence, and poor prognosis. Therefore, researching new drugs, improving the sensitivity of cervical cancer cells to cisplatin, and improving the effectiveness of cervical cancer treatment is the basis of this research. Aim: To investigate the inhibitory effect of curcumin on cisplatin-resistant cervical cancer Hela/DDP and SiHa/DDP cell lines. Materials and Methods: The study utilized cisplatin-resistant cervical squamous carcinoma (SiHa/DDP) and adenocarcinoma (Hela/DDP) cell lines. The cells in the experimental group were treated with 8.5 μM of curcumin, while the control group received only the culture medium. A colony formation assay was conducted to assess cell proliferation, with colonies stained using crystal violet; the number of colonies was then counted and compared between the two groups. Results : 1. In the Hela/DDP cell line, the control group formed an average of 507.7±15.70 colonies, whereas the experimental group, treated with curcumin, formed 112.3±16.17 colonies. The difference between the groups was statistically significant (p < 0.0001). 2. In the SiHa/DDP cell line, the control group had an average of 450.3±17.95 colonies, while the experimental group treated with curcumin had 198.3±13.05 colonies. This difference was also statistically significant (p < 0.0001). Conclusions 1. Curcumin significantly reduces the proliferation of cisplatin-resistant cervical squamous cell carcinoma (Hela/DDP) cells. 2. Curcumin significantly reduces the proliferation of cisplatin-resistant cervical adenocarcinoma (SiHa/DDP) cells.

Objective To study the correlation between the changes of matrix metalloproteinase-9(MMP-9)and neutrophil/lymphocyte ratio(NLR)before and after the revascularization of acute ischemic stroke(AIS),so as to find biomarkers to predict the bleeding transformation risk of AIS patients.Methods From February 2022 to December 2022,161 patients admitted to the Stroke Center of Qujing Hospital Affiliated to Kunming Medical University with AIS werre divided in to the hemorrhagic transformation group and the non-hemorrhagic transfor-mation groupand treated with revascularization(intravenous thrombolysis,endovascular treatment,combined the intravenous thrombolysis with endovascular treatment).Among them,there were 46 cases in the hemorrhagic transformation group and 115 cases in the non hemorrhagic transformation group.And the general data,NLR value and MMP-9 before and after the revascularization were compared between the two groups.Results There was no statistical difference in general data between the two groups(all P>0.05)except for C-reactive protein in hemorrhagic transformation group and in non-hemorrhagic transformation group(P<0.001).The white blood cells,neutrophils,neutrophil percentage,neutrophil absolute value,lymphocyte absolute value,NLR and MMP-9 value in hemorrhagic transformation group were significantly higher than those in non-hemorrhagic transformation group before the treatment and there was a statistical significance(P<0.05).After revascularization,the indexes of blood routine and MMP-9 were significantly higher than those before the revascularization,and the increase in hemorrhagic transformation group was more obvious than that in non-hemorrhagic transformation group and there was a statistical significance(P<0.001),The ROC curve showed that the area under the curve(AUC)of NLR and MMP-9 predicting bleeding transformation after AIS revascularization were 0.74 and 0.90.Conclusion NLR,MMP-9 are associated with the risk of bleeding transformation in AIS patients after the revascularization and can they can be used as the predictive factors for bleeding transformation risk.

OBJECTIVE To research the chemical components of Mongolian medicinal material Gentiana veitchiorum. METHODS Separation and purification were conducted using silica gel column chromatography, Sephadex LH-20 gel column chromatography, and preparative HPLC, and the compound structure was identified through spectral data and physicochemical constants. RESULTS Ten compounds were obtained from the separation of Gentiana veitchiorum. The compounds were respectively authenticated as 2,3-dihydroxybenzyl alcohol β-glucopyranoside(1), gentiopicroside(2), 2'-(O, m-Dihydroxybenzoyl) sweroside(3), isoorientin(4), isoorientin-3'-methyl ether(5), isovitexin(6), isoorientin-4’-O-glucopyranoside(7), isosoapin(8), ursolic acid(9), β-Sitosterol(10). CONCLUSION The compound 1 is authenticated as the new benzyl alcohol glycoside. The compound 10 is firstly separated from this medicinal plant.

In recent years,public health events caused by severe infectious diseases had a profound impact on human health,economic and social development.Drug stockpiling for infectious disease prevention and treatment is of great significance in improving the ability to respond to public health events.However,the drug stockpiling system of China for infectious disease prevention and treatment still needs to be improved.Based on the investigation and comparison of the current status of drug stockpiling for infectious disease prevention and treatment between China and the United States,this article proposes some suggestions according to China's specific circumstances for reference.

Objective To optimize the solid-phase synthesis process of phosphorodiamidate morpholino oligonucleotide(PMO)and determine the optimal reaction conditions.Methods The PMO tetramer PMO-TTTT was synthesized according to the reported reaction conditions,followed by purification through a semi-preparative high-performance liquid chromatography(HPLC)process.PMO-TTTT was structurally verified using nuclear magnetic resonance(NMR)and high-resolution mass spectrometry.With purified PMO-TTTT as a reference,a calibration curve was established,which subsequently guided the optimization of the reaction conditions for the solid-phase coupling reaction process,including the organic base,additives,duration of reaction and temperature.Under the optimized reaction condition,the anti-influenza A virus PMO sequence,PMO-flu,was synthesized and purified using a nucleic acid purification device.Results The optimal parameters for PMO solid-phase synthesis were determined.The organic base was N-ethylmorpholine,the additive was lithium iodide,the best temperature was 30 ℃,and the duration was 90 minutes.Conclusion The PMO solid-phase synthesis process has been established.LiI has been screened as a potent coupling reaction additive which could significantly boosts the efficiency of PMO solid-phase synthesis.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective To construct a fluorescent expression cell model of botulinum toxin type B light chain(BoNT/B,BLC),and evaluate the effect of small molecule compounds with this model.Methods The BLC gene was inserted into the fluorescent expression vector pEGFP-N1 to construct a recombinant plasmid before being transfected into the neural cell line Neuro-2a cells for expression.The fluorescence expression level of BLC-EGFP protein in the cells was observed under a fluorescence microscope,and the enzyme digestion activity and stability of BLC-EGFP in the cells were detected by Western blotting.Furthermore,the model was used to evaluate the effect of SRC kinase inhibitor KX2-391 on the intracellular stability of BLC-EGFP protein.Results The recombinant expression plasmid pEGFP-N1-BLC was constructed.It was found that the expression level of BCL-EGFP protein in Neuro-2a cells gradually increased over time,and that the intracellular substrate vesicle-associated membrane protein-2(VAMP-2)was cleaved after plasmid transfection.CHX was added to terminate protein synthesis after the plasmid was transfected for 12 h,and the intracellular level of BLC-EGFP did not change significantly within 72 h.Twenty-four hours of treatment with KX2-391 could significantly promote the intracellular degradation of BLC-EGFP protein.Conclusions A cell model of fluorescent expression of botulinum toxin type B light chain has been established,which provides a technical reserve for the subsequent study onthe intracellular persistence mechanism and intracellular antidote screening of botulinum toxin type B light chain.

Objective:To investigate the value of multi-stage dynamic contrast enhanced MRI (DCE-MRI) histogram in predicting survival of patients undergoing surgical treatment of colorectal cancer (CRC).Methods:The retrospective cohort study was conducted. The clinico-pathological data of 81 patients with CRC who were admitted to the Jiuquan City People′s Hospital from January 2018 to February 2019 were collected. There were 47 males and 34 females, aged (62±6)years. All patients underwent routine MRI and DCE-MRI examination to extract relevant imaging parameters. Observation indicators: (1) treatment, imaging examination and follow-up; (2) imaging factors influencing postoperative disease-free survival of patients with CRC. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Univariate and multivariate analyses were conducted using the COX proportional risk model. Pearson correlation test was used to analyze and exclude factors with correlation in univariate analysis, and the multi-variate analysis was conducted on the rest of factors. The Kaplan-Meier method was used to calculate survival rates, and Log-Rank test was used for survival analysis. Results:(1) Treatment, imaging examination and follow-up. All 81 patients underwent preoperative MRI plain scan, enhanced imaging, and diffusion weighted imaging. After complete examination, all patients underwent radical resection of CRC and received postoperative chemotherapy using the FOLFOX regimen. All 81 patients were followed up for 42(range, 11-61)months after surgery. The 1-, 3-, 5-year overall survival rate of 81 patients after surgery was 98.8%, 96.3%, 93.8%, respectively. During the follow-up period, 56 of the 81 patients survived from disease-free and 25 patients had disease progressed. (2) Imaging factors influencing postoperative disease-free survival of patients with CRC. Results of multivariate analysis showed that the kurtosis value and skewness value of positive enhancement integral (PEI) were independent imaging factors influencing postoperative disease-free survival of patients of CRC ( odds ratio=1.840, 1.243, 95% confidence interval as 1.403-2.412, 1.020-1.516, P<0.05). Taking the median values of kurtosis value and skewness value of PEI as 4.864 and 5.042 for further analysis. The postoperative 5-year disease-free survival rate of patients with kurtosis value of PEI <4.864 and ≥4.864 was 89.7% and 10.3%, showing a significant difference between them ( χ2=31.265, P<0.05). The postoperative 5-year disease-free survival rate of patients with skewness value of PEI<5.042 and ≥5.042 was 63.4% and 36.6%, showing a significant difference between them ( χ2=8.164, P<0.05). Conclusions:The kurtosis value and skewness value of PEI in DCE-MRI are independent imaging factors influencing postoperative disease-free survival of patients of CRC. The DCE-MRI histogram can effectively evaluate the postoperative prognosis of patients of CRC.

OBJECTIVES: To investigate the risk factors for necrotizing enterocolitis (NEC) in very preterm infants and establish a nomogram model for predicting the risk of NEC. METHODS: A total of 752 very preterm infants who were hospitalized from January 2015 to December 2021 were enrolled as subjects, among whom 654 were born in 2015-2020 (development set) and 98 were born in 2021 (validation set). According to the presence or absence of NEC, the development set was divided into two groups: NEC (n=77) and non-NEC (n=577). A multivariate logistic regression analysis was used to investigate the independent risk factors for NEC in very preterm infants. R software was used to plot the nomogram model. The nomogram model was then validated by the data of the validation set. The receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow goodness-of-fit test, and the calibration curve were used to evaluate the performance of the nomogram model, and the clinical decision curve was used to assess the clinical practicability of the model. RESULTS: The multivariate logistic regression analysis showed that neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding were independent risk factors for NEC in very preterm infants (P<0.05). The ROC curve of the development set had an area under the curve (AUC) of 0.833 (95%CI: 0.715-0.952), and the ROC curve of the validation set had an AUC of 0.826 (95%CI: 0.797-0.862), suggesting that the nomogram model had a good discriminatory ability. The calibration curve analysis and the Hosmer-Lemeshow goodness-of-fit test showed good accuracy and consistency between the predicted value of the model and the actual value. CONCLUSIONS Neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding are independent risk factors for NEC in very preterm infant. The nomogram model based on the multivariate logistic regression analysis provides a quantitative, simple, and intuitive tool for early assessment of the development of NEC in very preterm infants in clinical practice.
Asphyxia/complications* ; Child ; Enterocolitis, Necrotizing/etiology* ; Female ; Fetal Growth Retardation ; Humans ; Hypoalbuminemia ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Infant, Premature, Diseases/etiology* ; Nomograms ; Sepsis/complications*