BACKGROUND:Studies have shown that patients with premature ovarian failure have changes in the structure of intestinal flora and that imbalance of intestinal microbiota may be one of the important mechanisms in the development of premature ovarian failure. OBJECTIVE:To investigate the effect of Liuwei Dihuang Wan on oxidative stress and intestinal microbiota in premature ovarian failure mice induced by cyclophosphamide. METHODS:Forty-five female ICR mice were randomized into three groups:blank group(normal mice),model group(premature ovarian failure mice),and Liuwei Dihuang Wan group.A mouse model of premature ovarian failure was prepared by one-time intraperitoneal injection of cyclophosphamide(120 mg/kg)in the latter two groups.After successful modeling,the Liuwei Dihuang Wan group was intragastrically administered for 28 continuous days,and the other two groups were intragastrically administered with the same amount of normal saline for 28 days.Mouse body mass was recorded weekly and ovarian index was calculated.The development of mouse follicles was observed using hematoxylin-eosin staining.ELISA method was used to detect serum levels of anti-Mullerian hormone,estradiol,follicle stimulating hormone,superoxide dismutase,glutathione peroxidase,and malondialdehyde.Meanwhile,the gut microbiome of all mice was detected through 16S rDNA sequencing. RESULTS AND CONCLUSION:The mice in the model group had loose hair,decreased vigor and grip strength,almost no increase in body mass,and decreased ovarian index.Whereas,the mouse body mass and ovarian index were increased after treatment with Liuwei Dihuang Wan(P<0.05).The estrous cycle of mice in the model group was disorganized;Liuwei Dihuang Wan could restore the estrous cycle and reduce the number of atretic follicles in mice with premature ovarian failure.The serum levels of follicle stimulating hormone and malondialdehyde in the model group significantly increased(P<0.01),while the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase significantly decreased(P<0.01).Liuwei Dihuang Wan could significantly decrease the serum levels of follicle stimulating hormone and malondialdehyde(P<0.01),and increase the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase.According to the 16S rDNA sequencing results,Liuwei Dihuang Wan could regulate the abundance and diversity of intestinal microbiota,and increase the relative abundance of beneficial bacteria.KEGG pathway analysis showed that the intestinal microbiota and metabolic pathways,biosynthesis of secondary metabolites,microbial metabolism in different environments,and biosynthesis of amino acids were regulated by Liuwei Dihuang Wan.To conclude,the changes in the structure of intestinal microbiome may be one of the potential mechanisms of Liuwei Dihuang Wan in treating premature ovarian failure.Liuwei Dihuang Wan can regulate the structure of intestinal microbiome,increase the number of beneficial bacteria,reduce the number of harmful bacteria,and thus improve the balance of intestinal microbiota.This regulatory effect helps to reduce oxidative stress levels and further inhibit ovarian oxidative stress in mice with premature ovarian failure.

Objective To establish and internally validate a predictive model for poorly differentiated adenocarcinoma based on CT imaging and tumor marker results. Methods Patients with solid and partially solid lung nodules who underwent lung nodule surgery at the Department of Thoracic Surgery, the Affiliated Brain Hospital of Nanjing Medical University in 2023 were selected and randomly divided into a training set and a validation set at a ratio of 7:3. Patients' CT features, including average density value, maximum diameter, pleural indentation sign, and bronchial inflation sign, as well as patient tumor marker results, were collected. Based on postoperative pathological results, patients were divided into a poorly differentiated adenocarcinoma group and a non-poorly differentiated adenocarcinoma group. Univariate analysis and logistic regression analysis were performed on the training set to establish the predictive model. The receiver operating characteristic (ROC) curve was used to evaluate the model's discriminability, the calibration curve to assess the model's consistency, and the decision curve to evaluate the clinical value of the model, which was then validated in the validation set. Results A total of 299 patients were included, with 103 males and 196 females, with a median age of 57.00 (51.00, 67.25) years. There were 211 patients in the training set and 88 patients in the validation set. Multivariate analysis showed that carcinoembryonic antigen (CEA) value [OR=1.476, 95%CI (1.184, 1.983), P=0.002], cytokeratin 19 fragment antigen (CYFRA21-1) value [OR=1.388, 95%CI (1.084, 1.993), P=0.035], maximum tumor diameter [OR=6.233, 95%CI (1.069, 15.415), P=0.017], and average density [OR=1.083, 95%CI (1.020, 1.194), P=0.040] were independent risk factors for solid and partially solid lung nodules as poorly differentiated adenocarcinoma. Based on this, a predictive model was constructed with an area under the ROC curve of 0.896 [95%CI (0.810, 0.982)], a maximum Youden index corresponding cut-off value of 0.103, sensitivity of 0.750, and specificity of 0.936. Using the Bootstrap method for 1000 samplings, the calibration curve predicted probability was consistent with actual risk. Decision curve analysis indicated positive benefits across all prediction probabilities, demonstrating good clinical value. Conclusion For patients with solid and partially solid lung nodules, preoperative use of CT to measure tumor average density value and maximum diameter, combined with tumor markers CEA and CYFRA21-1 values, can effectively predict whether it is poorly differentiated adenocarcinoma, allowing for early intervention.

Tislelizumab is a next-generation PD-1 monoclonal antibody developed to overcome the limitations of earlier immune checkpoint inhibitors. By eliminating Fcγ receptor binding, it avoids macrophage-mediated T-cell clearance and enhances the antitumor immune response. Unlike conventional PD-1 inhibitors, tislelizumab binds to PD-1 in a way that more closely mimics the natural PD-L1 interaction, potentially improving efficacy and reducing immune-related toxicity. This review highlights its structural advantages, clinical efficacy across multiple cancers, and recent global regulatory approvals. We also discuss key pharmacokinetic features and current challenges, including the need for predictive biomarkers, immune-related adverse events, and combination therapy strategies. Together, these insights may guide the more effective and safer use of tislelizumab in cancer immunotherapy.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective To explore the risk factors for pain after puncturing localization using Hookwire needles for preoperative pulmonary nodules resections,providing theoretical evidences for reducing post-localization complications in patients.Methods For cross-sectional analysis,141 patients undergoing preoperative CT-guided localization using Hookwire needles for preoperative single pulmonary nodule resections in Nanjing Chest Hospital from February 2024 to May 2024.The pain levels of the patients after localization were recorded according to the numerical rating scales(NRS).Comparions the pain levels between patients' genders,ages,BMI,sides,number of intercostals at the puncture point,depths of puncture needle penetration through the chest wall,depths of puncture needle penetration in the lungs,whether the needles were inserted tightly against the ribs,and whether the needle were inserted tightly against the scapula.The influencing factors causing pain were explored by univariate analysis as well as ordered Logistic analysis.Results All 141 patients were successfully localized without serious complications,and the results of univariate analysis showed that BMI,depth of penetration within the thoracic wall of the puncture needle,whether or not the needle was inserted tightly against the ribs,and whether or not it was inserted tightly against the scapula were correlated with the post-positioning pain,and the differences were statistically significant from each other(P＜0.1).Ordered Logistic regression analysis showed that the depth of penetration within the chest wall of the puncture needle(OR=1.484,95％CI=0.033～0.758,P＜0.05),and whether or not the needle was inserted tightly against the rib cage(OR=9.440,95％CI=1.434～3.056,P＜0.05)and tight scapular entry(OR=9.994,95％CI=0.957～3.646,P＜0.05)were risk factors for pain after positioning.Conclusion The deepth of localization needle penetrating in the chest wall and puncturing close to the edge of scapula and ribs are the risk factors for pain after puncturing localization using a Hookwire needle for preoperative pulmonary nodules resection.

Sodium glucose cotransporter(SGLT)2 inhibitors,initially developed as antihyperglycemic agents,have demonstrated remarkable cardioprotective effects in numerous clinical trials and are now utilized in the treat-ment of heart failure across a range of ejection fractions.SGLT2 is predominantly expressed in the renal proximal tubules,brain,and epicardial adipose tissue within the human body.Research indicates that the protective effects of SGLT2 inhibi-tors in heart failure are linked to their direct modulation of SGLT2 receptors in both the kidneys and epicardial adipose tis-sue.Furthermore,SGLT is also present in the brain,and recent studies have revealed that SGLT2 inhibitors can enhance sympathetic activity in patients with metabolic syndrome,suggesting a potential neuroregulatory role.Given that excessive activation of the sympathetic nervous system can contribute to the onset and progression of heart failure,this paper reviews the neural regulatory mechanisms of SGLT2 inhibitors to provide insights for a deeper understanding of heart failure and to optimize their clinical application.

Objective To compare regression models for age estimation constructed based on the Pulp Dentinal Index(PDI)of the first permanent molars and explore a more accurate and applicable novel method.Methods A total of 900 Cone Beam Computed Tomography(CBCT)image datasets from adult Han Chinese individuals(455 males and 445 females)residing in Sichuan province,China,were collected from the Affiliated Hospital of North Sichuan Medical College.The PDI of the first permanent molars were measured using Mimics software.Regression analysis was performed with age as the dependent variable and PDI as the independent variable to establish and validate the optimal mathematical model for age estimation.Results Strong correlations were observed between the PDI of all four first permanent molars and age,with the correlation being stronger for maxillary teeth compared to mandibular teeth,and the highest correlation found in the left maxillary first molar among females(r=0.881).Significant differences in PDI were identified between maxillary and mandibular positions as well as between genders(P＜0.05),but not between left and right positions(P＞0.05).Among the 11 mathematical models constructed,the cubic regression model outperformed others,with the left maxillary first molar model demonstrating the best performance(Age=73.93-70.79x-68.75x2+94.33x3),yielding a mean absolute error(MAE)of 4.88 years.Conclusion Among the 11 regression models constructed in this study based on CBCT-measured PDI values of the first permanent molars,the cubic regression model exhibited the highest accuracy,with an MAE of 4.88 years.

Atherosclerotic cardiovascular diseases(ASCVD)are chronic progressive diseases characterized by endothelial dysfunction,and their traditional therapies have limitations.In recent years,nanocarrier systems have demonstrated significant advantages in targeted delivery,enhancing drug safety and efficacy,thereby offering new strategies for precise diagnosis and treatment of ASCVD.Nanomaterials,including polymer nanoparticles,lipid nanoparticles,inorganic nanoparticles and bio-inspired nanoparticles,can effectively intervene key pathological processes of ASCVD.They achieve therapeutic effects by regulating macrophage balance,preserving endothelial cell function,maintaining smooth muscle cell contractile phenotype and modulating platelet activity.This review summarizes the application characteristics and research progress of different types of nanomaterials in the prevention and treatment of ASCVD,and provides insights into the challenges and future prospects of this field.

Objective:To evaluate the effect of intraoperative optimization of regional cerebral oxygen saturation(rSO 2C) intervention on postoperative delirium(POD) in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass(CPB). Methods:Two hundred and seventy-three pediatric patients of both sexes, aged 28 days-6 yr, with American Society of Anesthesiologists Physical Status classification ≤Ⅳ, scheduled for elective cardiac surgery under CPB, were divided into intervention group( n=136) and control group( n=137) based on the computer random coding. In intervention group, optimized intervention measures were given when rSO 2C was below 75% of the baseline value for more than 1 min. In control group, rSO 2C was not monitored during operation, and intraoperative management was performed according to the routine monitoring indicators of pediatric cardiac surgery under CPB. The occurrence of POD within 7 days after operation was evaluated, and the duration and first occurrence time of POD were recorded. Results:Compared with control group, no significant change was found in the incidence of POD( P>0.05), the first occurrence time of POD was significantly prolonged, and the duration of POD was shortened in intervention group( P<0.05). Conclusions:Intraoperative optimization of rSO 2C intervention can delay the time to the first occurrence of POD and shorten the duration in pediatric patients undergoing cardiac surgery under CPB.