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.

Objective:To analyze the efficacy and safety of a modified cystic wall peeling method combined with Zhang′s tension-reduced suture in the treatment of sebaceous cysts.Methods:Twenty-eight patients with sebaceous cysts, 22 males and 6 females, aged 18-44 (27.3±5.7) years, who were treated with modified cystic wall peeling combined with Zhang′s tension-reduced suture at the 940 Hospital of the Joint Logistic Support Force from July 2022 to October 2023 were prospectively included. A simple cyst peeler was self-made using a sterile tear duct probe with a diameter of 0.5 mm and a length of 7.3 cm. The skin was incised directly when the cyst protruded <5 mm from the skin surface; a shuttle incision was used to remove excess skin when the cyst protruded ≥5 mm from the skin surface. After incision of the skin, the cavity between the cyst wall and the surrounding normal tissue at the incision site was peeled off with ophthalmic scissors, and the cyst peeler was inserted into the cavity up to the bottom of the cyst and rotated along the cystic wall for 1 week to achieve complete blunt peeling within the cyst from the surrounding normal tissue. After the peeling was completed, the sebaceous cyst was squeezed by hand to discharge the cystic wall and its contents; if it could not be discharged, the cyst contents were released first and then squeezed. Absorbable sutures were used to close the residual cavity with Zhang′s tension-reduced suture, and then the incision was closed intermittently with non-absorbable sutures, and the surgical site was bandaged with pressure. Postoperative follow-up was performed for 1 year by telephone or WeChat to assess the overall postoperative effective rate, overall satisfactory rate, modified sebaceous cyst score and incidence of incisional scarring hyperplasia, and to record the occurrence of adverse reactions.Results:The preoperative modified sebaceous cyst score of 28 patients was (5.39±1.34) scores, which decreased to (0.25±0.59) scores one year after surgery, and the difference was statistically significant ( P<0.001). The overall postoperative effective rate was 100% (28/28), and the overall satisfactory rate was 96.4% (27/28), and all patients had no scarring hyperplasia. One patient had localized epidermal necrosis at the skin edge of the chest incision, one patient had erythema and scattered ecchymosis in the surgical area of the buttocks, and one patient had pain at the surgical site of the left upper extremity, which were cured after symptomatic treatment. Conclusion:Modified cystic wall peeling combined with Zhang′s tension-reduced suture is effective in the treatment of sebaceous cysts, and the incidence of adverse effects is low.

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.

Objective:To analyze the efficacy and safety of a modified cystic wall peeling method combined with Zhang′s tension-reduced suture in the treatment of sebaceous cysts.Methods:Twenty-eight patients with sebaceous cysts, 22 males and 6 females, aged 18-44 (27.3±5.7) years, who were treated with modified cystic wall peeling combined with Zhang′s tension-reduced suture at the 940 Hospital of the Joint Logistic Support Force from July 2022 to October 2023 were prospectively included. A simple cyst peeler was self-made using a sterile tear duct probe with a diameter of 0.5 mm and a length of 7.3 cm. The skin was incised directly when the cyst protruded <5 mm from the skin surface; a shuttle incision was used to remove excess skin when the cyst protruded ≥5 mm from the skin surface. After incision of the skin, the cavity between the cyst wall and the surrounding normal tissue at the incision site was peeled off with ophthalmic scissors, and the cyst peeler was inserted into the cavity up to the bottom of the cyst and rotated along the cystic wall for 1 week to achieve complete blunt peeling within the cyst from the surrounding normal tissue. After the peeling was completed, the sebaceous cyst was squeezed by hand to discharge the cystic wall and its contents; if it could not be discharged, the cyst contents were released first and then squeezed. Absorbable sutures were used to close the residual cavity with Zhang′s tension-reduced suture, and then the incision was closed intermittently with non-absorbable sutures, and the surgical site was bandaged with pressure. Postoperative follow-up was performed for 1 year by telephone or WeChat to assess the overall postoperative effective rate, overall satisfactory rate, modified sebaceous cyst score and incidence of incisional scarring hyperplasia, and to record the occurrence of adverse reactions.Results:The preoperative modified sebaceous cyst score of 28 patients was (5.39±1.34) scores, which decreased to (0.25±0.59) scores one year after surgery, and the difference was statistically significant ( P<0.001). The overall postoperative effective rate was 100% (28/28), and the overall satisfactory rate was 96.4% (27/28), and all patients had no scarring hyperplasia. One patient had localized epidermal necrosis at the skin edge of the chest incision, one patient had erythema and scattered ecchymosis in the surgical area of the buttocks, and one patient had pain at the surgical site of the left upper extremity, which were cured after symptomatic treatment. Conclusion:Modified cystic wall peeling combined with Zhang′s tension-reduced suture is effective in the treatment of sebaceous cysts, and the incidence of adverse effects is low.

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 clinical effects of ultra-pulsed fractional carbon dioxide laser (UFCL) in the treatment of mild to moderate microstomia after burns. Methods: A retrospective observational study was conducted on 19 patients with mild to moderate microstomia after burns who were admitted to Inner Mongolia Baogang Hospital from January 2018 to January 2022, including 15 males and 4 females aged (35±14) years. Patients had an average course of 71 d of microstomia, with 8 cases of moderate microstomia and 11 cases of mild microstomia. All the patients received UFCL treatment every 2-3 months until the microstomia was corrected or the treatment bottleneck was reached. The times of UFCL treatment for patients and the time interval from the last treatment to the last follow-up were recorded. Before the first treatment and at the last follow-up, the opening degree of mouth (finger measurement method), oral gap width, and the distance between the upper and lower incisors during mouth opening were recorded. Before the first treatment and at the last treatment, the new Vancouver scar scale (VSS) was used to evaluate the scar. At the last follow-up, the degree of satisfaction was evaluated by the Likert 5 scale by the patients themselves, and the satisfaction ratio was calculated; the adverse reactions such as pigmentation, blisters, infection, and persistent erythema in the treatment area were counted. Data were statistically analyzed with Mann-Whitney rank sum test or paired sample t test. Results: Patients received UFCL treatment of 3 (2, 6) times. The interval from the last treatment to the last follow-up was 26 months at most and 4 months at least. At the last follow-up, the opening degree of mouth of patients was significantly improved than that before treatment (Z=4.68, P<0.01). At the last follow-up, the oral gap width of patients was (35±6) mm, and the distance between upper and lower incisors during mouth opening was (3.2±0.4) cm, which was significantly improved compared with those before treatment (with t values of 10.73 and 18.97, respectively, P<0.01). The VSS score after the last treatment was 4.1±1.6, which was significantly better than that before treatment (t=22.96, P<0.01). At the last follow-up, the satisfaction ratio of patients with treatment was 18/19, and no pigmentation, blisters, infection, persistent erythema, and other adverse reactions of all patients in the treatment area occurred, however, one of the patients reported that the disease recurred about half a year after treatment. Conclusions: UFCL is an effective method for treating mild to moderate microstomia after burns, with which patients are highly satisfied, and it is worth of further study and promotion.
Blister ; Burns/therapy* ; Cicatrix/therapy* ; Female ; Humans ; Lasers, Gas/therapeutic use* ; Male ; Microstomia ; Treatment Outcome

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*