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.

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.

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.

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.