When inflammation is continuously activated or dysregulated， it can induce chronic tissue injury and organ dysfunction， and participate in the occurrence and development of various inflammatory diseases such as atherosclerosis and inflammatory bowel disease. Owing to high targeting， long-acting efficacy and programmability， nucleic acid drugs provide a new direction for the treatment of inflammatory diseases. This article reviews the classification， mechanism of action and application progress of nucleic acid drugs in inflammatory diseases. It is found that small interfering RNA （siRNA） can specifically cut target mRNA through RNA interference to achieve inhibiting the expression of the target protein； antisense oligonucleotide （ASO） can inhibit target protein expression by inducing microRNA （miRNA） degradation or regulating splicing processes； miRNA can achieve network intervention by regulating multiple inflammatory target genes. At present， important breakthroughs have been made in the field of inflammatory diseases with siRNA drugs including Lumasiran， Nedosiran （for primary hyperoxaluria 1） and Inclisiran （for atherosclerosis）， ASO drugs including Donidalorsen （for hereditary angioedema）， Volanesorsen and Olezarsen （for familial chylomicronemia syndrome） and Lademirsen （for Alport syndrome）， as well as miRNA drugs including Obefazimod （for inflammatory bowel disease） and Remlarsen （for pathological fibrosis）. These drugs are expected to become a new generation of anti-inflammatory therapeutic strategies and bring more precise and efficient treatment options for patients with chronic inflammation and fibrotic diseases.

Purpose: The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity. Materials and Methods: The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells. Results: Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis. Conclusion Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

Objective To analyze the clinical characteristics of immune checkpoint inhibitor (ICI)-related hypophysitis. Methods A retrospective analysis was conducted on patients diagnosed with ICI-related hypophysitis and treated at the Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, between January 2020 and March 2025. Clinical manifestations and prognosis of patients were analyzed. Results Eleven patients with ICI-related hypophysitis were included. The average age was (62.27±7.63) years, and 9 patients (81.82%) were male. The median time to onset was 9.1 months, and the median number of treatment cycles received was 5. The primary initial symptoms were fatigue and anorexia. Hyponatremia was present in 3 patients (27.27%). Evaluation of anterior pituitary function revealed adrenocorticotropic hormone deficiency as the most common manifestation (90.91%, 10/11), followed by hyperprolactinemia (81.82%, 9/11). Posterior pituitary function remained normal in all patients. Pituitary magnetic resonance imaging showed no abnormality in 4 patients (44.44%). Thyroid dysfunction was observed in 6 patients (54.55%), one of whom (9.09%) also exhibited pancreatic endocrine dysfunction. The average follow-up duration was 36.5 months. Eight patients (72.73%) were alive at the last follow-up. None of the patients recovered their pituitary hormone function. Conclusions Endocrine adverse events induced by ICIs can involve multiple glandular systems. Clinicians should be highly vigilant for the possibility of ICI-induced hypophysitis in patients receiving ICIs who present with symptoms such as fatigue, anorexia, and hyponatremia.

With advancements in in vitro culture techniques, the morula has emerged as a promising candidate for selective embryo transfer due to its critical compaction phase. The compaction process involves not only structural reorganization but also complex intercellular signaling mechanisms that significantly influence embryonic developmental potential and cellular fate determination. Clinical data reveal comparable live birth rates between day 4 morula transfers and day 5 blastocyst transfers, coupled with reduced in vitro culture duration. However, challenges persist regarding standardized evaluation criteria and long-term safety confirmation. Current morphological assessment methods exhibit inherent subjectivity, while emerging technologies integrating genetic screening, metabolic analysis, and time-lapse imaging show potential for enhanced selection accuracy. Personalized synchronization assessments, including endometrial receptivity analysis, may further optimize transfer protocols. This study focuses on day 4 embryo transfer, systematically reviewing its embryonic development processes, evaluation protocols, comparative outcomes of transferred embryos, and research advances in frozen-thawed embryo transfer. The study aims to deepen scientific understanding of day 4 embryo transfer and promote its adoption as a critical option in personalized reproductive medicine, thereby enhancing clinical success rates and safety.

Objective:To establish a day 4 embryo evaluation protocol by analyzing embryonic characteristics affecting blastocyst formation, and validate its clinical effectiveness.Methods:This retrospective cohort study included clinical data from 1 037 patients who underwent fresh in vitro fertilization and embryo transfer (IVF-ET) on day 4 in Center for Reproductive Medicine of Xingtai Meihe Reproductive and Genetic Hospital between January 2018 and April 2024. Morphological assessments were performed at (92±2) h post-fertilization. After excluding 1 326 embryos selected for fresh transfer, 2 723 embryos underwent blastocyst culture. To address selection bias in transferred embryos, the scoring system was primarily based on high-quality blastocyst formation rates. Multivariate binary regression analysis evaluated how day 4 developmental stage, fragmentation rate, stage-specific cleavage patterns, multinucleation/vacuolization affected transferable blastocyst formation rate and high-quality blastocyst rate. Regression coefficients determined parameter weights for high-quality blastocyst formation, establishing a day 4 embryo scoring protocol that compared outcomes across different grades. The scoring system was validated by comparing transferable blastocyst formation rate, high-quality blastocyst rate, and implantation rate among different day 4 embryo grades. All embryos were further rescored according to three previously reported evaluation schemes [Feil 2008, Gemma 2015, and European Society of Human Reproduction and Embryology (ESHRE) 2011]. The predictive values of these three day 4 scoring systems and the day 4 scoring system established in this study were compared using the area under the curve (AUC) receiver operating characteristic (ROC) curve in predicting the formation rate of transferable blastocyst, the formation rate of high-quality blastocyst, and implantation rate. Results:In the prediction of high-quality blastocyst formation, early blastocyst showed the highest influence weight compared to embryos with the ratio of blastomere numbers on day 4 to those on day 3 (BNR) <1.2 ( B=3.398, OR=29.915, P<0.001), followed by fragmentation <10% versus ≥50% ( B=1.263, OR=3.535, P<0.001), a stage-specific cleavage pattern ( B=0.903, OR=2.467, P=0.005), and absence of multinucleation or vacuoles ( B=0.797, OR=2.218, P=0.007). Using the newly developed day 4 scoring system, embryos were graded A, B, C, D, E. Transferable blastocyst formation rates were 88.57% (279/315), 76.99% (241/313), 56.11% (280/499), 40.27% (238/591) and 14.22% (143/1 005), respectively; high-quality blastocyst rates were 51.42% (162/315), 35.46% (111/313), 20.04% (100/499), 9.47% (56/591) and 3.98% (40/1 005). All inter-group differences were statistically significant (all P<0.005). Implantation rates for transferred embryos of grades A-E declined sequentially: 63.18% (381/603), 56.19% (322/573), 38.29% (54/141), 26.53% (13/49) and 9.67% (3/31). The day 4 embryo scoring system proposed in this study demonstrated significantly higher predictive efficacy for transferable blastocyst formation rate (AUC=0.812), high-quality blastocyst formation rate (AUC=0.804), and implantation rate (AUC=0.603) compared with Feil 2008 (AUC=0.797, P<0.001; AUC=0.781, P<0.001; AUC=0.585, P<0.001), Gemma 2015 (AUC=0.773, P<0.001; AUC=0.771, P<0.001; AUC=0.542, P=0.006), and ESHRE 2011 (AUC=0.710, P<0.001; AUC=0.745, P<0.001; AUC=0.592, P<0.001). We also observed the presence of pseudo-compacted embryo, whose transferable blastocyst formation rate [38.28% (49/128)] and high-quality blastocyst formation rate [7.03% (9/128)] were similar to those of cleavage-stage embryos with a BNR≥1.2. Conclusion:The established day 4 morphological assessment system reliably predicts the potential to transferable blastocyst and high-quality blastocyst, and effectively forecasts implantation rates.

Objective:To analyze the clinical features associated with pelvic lymph node metastasis(PLNM)in prostate cancer and to construct a preoperative prediction model for PLNM,thereby reducing unnecessary extended pelvic lymph node dissection(ePLND).Methods:Based on predefined inclusion and exclusion criteria,344 patients who underwent radical prostatectomy and ePLND at the First Affilia-ted Hospital of Zhengzhou University between 2014 and 2024 were retrospectively enrolled,among whom,77 patients(22.4％)were pathologically confirmed to have lymph node-positive disease.The clinical characteristics,MRI reports,and pathological results were collected.The data were then randomly divi-ded into a training cohort(241 cases,70％)and a validation cohort(103 cases,30％).Univariate and multivariate Logistic regression analysis were employed to construct a preoperative prediction model for PLNM.Results:Univariate Logistic regression analysis revealed that total prostate specific antigen(tPSA)(P=0.021),free prostate specific antigen(fPSA)(P=0.002),fPSA to tPSA ratio(fPSA/tPSA)(P=0.011),percentage of positive biopsy cores(P＜0.001),prostate imaging reporting and data system(PI-RADS)score(P=0.004),biopsy Gleason score ≥8(P=0.005),clinical T stage(P＜0.001),and MRI-indicated lymph node involvement(MRI-LNI)(P＜0.001)were significant predictors of PLNM.Multivariate Logistic regression analysis demonstrated that the percentage of positive biopsy cores(OR=91.24,95％CI:13.34-968.68),PI-RADS score(OR=7.64,95％ CI:1.78-138.06),and MRI-LNI(OR=4.67,95％ CI:1.74-13.24)were independent risk factors for PLNM.And a novel nomogram for predicting PLNM was developed by integrating all these three variables.Com-pared with the individual predictors:percentage of positive biopsy cores[area under curve(AUC)=0.806],PI-RADS score(AUC=0.679),and MRI-LNI(AUC=0.768),the multivariate model incor-porating all three variables demonstrated significantly superior predictive performance(AUC=0.883).Consistently,calibration curves and decision curve analyses confirmed that the multivariable model had high predictive accuracy and provided significant net clinical benefit relative to single-variable models.And using a cutoff of 6％,the multiparameter model missed only approximately 5.2％of PLNM cases(4/77),while reducing approximately 53％of ePLND procedures(139/267),demonstrating favorable predictive efficacy.Conclusion:Percentage of positive biopsy cores,PI-RADS score and MRI-LNI are independent risk factors for PLNM.The constructed multivariate model significantly improves predictive efficacy,offering a valuable tool to guide clinical decisions on ePLND.

Purpose To analyze the expression of SNAP23 in esophageal squamous cell carcinoma(ESCC)and its influence on invasion of ESCC cells.Methods A total of 41 cases of ESCC and paired normal adjacent tissue(NAT)were collected.The expression and localization of SNAP23 were detected by immunohistochemical EnVision method.The differences of SNAP23 expression levels between ESCC tissues and NAT tissues were compared to analyze the relationship between SNAP23 expression and clinicopathological characteristics.The expression level of SNAP23 in human immortalized esophageal epithelial cells SHEE and ESCC cell lines TE-1,TE-13 and KYSE150 were detected by Western blot.Lentiviral vector transfection technique was used to construct stable transfection cell lines with knock-down and overexpression of SNAP23 gene.The effect of SNAP23 on invasion of ESCC cell line TE-13 was evaluated by cell invasion experiment.Results The expression of SNAP23 in ESCC was significantly higher(53.7％,22/41)than that in the NAT group(19.5％,8/41),the difference was statistically significant(x2=10.303,P＜0.01).The expression level of SNAP23 in ESCC tissues was significantly correlated with maximum tumor diameter(x2=4.193,P＜0.05)and invasion depth(x2=7.264,P＜0.05),but was not correlated with patient gender,age,tumor site,tumor type,pathologic grade,vascular embolus,nerve invasion and lymph node metastasis(P＞0.05).Compared with human immortalized esophageal epithelial cells SHEE,SNAP23 was highly expressed in ESCC cell lines(P＜0.000 1).Compared with the sh-NT group,the invasion of ESCC cell line TE-13 was inhibited when SNAP23 expression was knocked down(P＜0.000 1);compared with the Vector group,the invasion of ESCC cell line TE-13 was enhanced after overexpression of SNAP23(P＜0.000 1).Conclusion SNAP23 is highly expressed in ESCC tis-sue and cell lines,and its expression level in ESCC tissues is positively correlated with tumor maximum diameter and invasion depth;SNAP23 promotes the invasion of ESCC cells.

Objective:This article introduces a novel technique for totally laparoscopic, right thoracic approach, esophagojejunostomy for digestive tract reconstruction.Methods:A retrospective analysis was conducted on the clinical data of patients with adenocarcinoma of the esophagogastric junction who successfully underwent totally laparoscopic esophagojejunostomy via the right thoracic approach at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between February 2022 and March 2022.The surgical procedure was performed as follows:(1)Following total laparoscopic resection of the gastric tumor and lymph node dissection, the specimen was transected distal to the tumor margin. The specimen was then placed into a retrieval bag and extracted through the umbilical observation port.(2)Dissection was continued through the esophageal hiatus to mobilize the esophagus. The tumor-bearing tissue, along with the esophagus, was delivered into the thoracic cavity via the esophageal hiatus.(3)The jejunum was transected 20 cm distal to the ligament of Treitz. The distal Jejunum was mobilized for 15-20 cm and subsequently delivered into the thoracic cavity through the esophageal hiatus.(4)A Roux-en-Y jejunojejunostomy was constructed 45-50 cm distal to the cut end of the distal jejunal limb; the mesenteric defect was closed, and the duodenal stump was reinforced.(5)The patient was repositioned into the left lateral decubitus position. Port placement was established as follows: the observation port at the 7th intercostal space (ICS) in the right midaxillary line, the main operating port at the 4th ICS in the anterior axillary line, and the assistant operating port at the 9th ICS in the scapular line.(6)The main operating port incision was enlarged. Using a purse-string instrument, the esophagus was clamped and transected at least 5 cm proximal to the upper tumor margin, and the specimen was removed. (7)The distal jejunum was delivered into the thoracic cavity via the esophageal hiatus. Under total laparoscopic visualization, esophagojejunostomy was completed.Results:Both patients who underwent totally laparoscopic esophagojejunostomy via the right thoracic cavity successfully completed the procedure without conversion to laparotomy, unplanned reoperation, or any intraoperative/postoperative complications. The patients recovered well postoperatively, with no evidence of abdominal or thoracic hemorrhage. Postoperative computed tomography (CT) scans of the chest and abdomen confirmed the absence of anastomotic leakage or other related complications.Conclusions:The esophagojejunostomy was performed totally laparoscopically via the right thoracic cavity. This approach overcomes the drawback of significant trauma associated with open surgery while ensuring safe esophageal resection margins and thorough lymph node dissection. This technique offers advantages including minimal invasiveness, accelerated postoperative recovery, and a reduced incidence of reflux esophagitis. To our knowledge, no similar method of digestive tract reconstruction has been reported in the literature. Its novelty and clinical potential may offer new therapeutic options for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG).

Objective To compare the efficacy and complications of cupric ion electrochemical therapy and selective suprahemorrhoid resection and stapling surgery for the treatment of grade Ⅲ-Ⅳhemorrhoids.Methods 204 patients with grade Ⅲ-Ⅳ mixed hemorrhoids admitted to our hospital from September 2022 to October 2023 were included as the study subjects.They were divided into two groups using numerical method,with 102 cases in each group.The observation group received copper ion electrochemical therapy,while the control group received selective hemorrhoid mucosal resection and stapling surgery.Compare the surgical outcomes,efficacy,pain scores,anal function scores,quality of life index scores,and incidence of complications between two groups.Results There was no statistically significant difference in gender,age,hemorrhoid grade,surgical time,and hospitalization period between the observation group and the control group(P＞0.05),but the intraoperative blood loss in the observation group was less than that in the control group[(11.37±5.32)ml and(26.72±14.24)ml],and the difference between the two groups was statistically significant(P＜0.05).The severity of pain in the observation group was lower than that in the control group on the 1st and 7th day after surgery(P＜0.05);There was no statistically significant difference in the Wexner anal incontinence scores between the two groups at 1 and 8 weeks after surgery(P＞0.05).The observation group had a better gastrointestinal quality of life index(GIQLI)score than the control group at 2 weeks after surgery[(20.92±4.63)and(26.77±5.03)scores,P＜0.05],and there was no statistically significant difference between the two groups at 8 weeks[(4.38±0.90)and(4.68±1.41)mm,P＞0.05].The total incidence of postoperative complications in both groups was statistically significant(8.8％vs 20.6％,P＜0.05).An average follow-up of six months showed no recurrence.Conclusion Cupric ion electrochemical therapy for mixed hemorrhoids is safe,effective,and has no serious complications,providing a more convenient and minimally invasive treatment method.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.