Objective The objective of this study was to establish a mouse model of allergic rhinoconjunctivitis and investigate the role of the NLRP3 signaling pathway in allergic rhinoconjunctivitis.Methods Thirty-three female C57 mice(SPF)were randomLy divided into 3 groups:the control group,the experimental group,and the NLRP3-/-group.On days 0,4,7,14,and 21,the experimental group and NLRP3-/-group received a 0.2 mL intraperitoneal injection of medicine containing OVA(100 μg)and adjuvant Al(OH)3(4 mg),respectively.After an interval of 3 days,each eye and nose were dosed with 10 μL of 5%OVA for five consecutive days a week to induce allergic symptoms.During sensitization and excitation stages,the control group was replaced with an equiva-lent amount of PBS.Ocular and nasal symptoms were observed and scored.The levels of OVA-specific IgE,IL-4,IL-17,and IL-18 in serum were measured using ELISA,while changes in palpebral conjunctiva and nasal mucosa were assessed by hematoxylin-eosin staining.The expression of NLRP3 mRNA in conjunctival tissue and nasal mucosa was determined using real-time PCR analysis.Statistical analysis was performed using SPSS17.0 software with P<0.05 considered as statistically significant difference.Results The experimental group and NLRP3-/-group exhibited induced nasal and ocular allergic symptoms.In the experimental group,the duration of nasal allergy symptoms was(10.500±1.080)days,while the duration of eye allergy symptoms was(20.300±2.058)days.In the NLRP3-/-group,the duration of nasal allergy symptoms was(13.400±1.955)days,and for eye allergy symp-toms it was(20.900±2.132)days.The duration of nasal allergies in the NLRP3-/-group significantly exceeded that in the experimental group(P<0.05),whereas there were no significant differences observed in eye allergy durations between these two groups(P>0.05).Levels of OVA-specific IgE,IL-4,and IL-17 were significantly higher in both the experimental and NLRP3-/-groups compared to those in the control group(P<0.05).Additionally,serum IL-18 content increased significantly in the experimental group when compared with both control and NLRP3-/-groups(P<0.05).Conjunctival tissue lesions as well as nasal mucosa damage were evident in both experimental and NLRP3-/-groups.mRNA expression levels of NLRP3 within conjunctival tissue and nasal mucosa from the experimental group showed a significant increase when compared to those from both control and NLRP3-/-groups(P<0.05).Conclusion Allergic rhinoconjunctivitis pathogenesis is influenced by various factors;however,the involvement of NLPR3 signaling pathway promotes its development.

Objective: To determine whether proactive molecular risk classifier for endometrial cancer (ProMisE) could be used to assess the prognosis of patients with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC) treated with levonorgestrelreleasing intrauterine system (LNG-IUS). Methods: A retrospective cohort study was conducted among 93 AEH or early-stage EC patients who received LNG-IUS to preserve fertility . By immunohistochemistry and gene sequencing, 4 subtypes of ProMisE were identified (p53 wild type [p53 wt], mismatch repairdeficient [MMRd], p53-abnormal, and POLE-mutated). The primary outcome was the time to complete response (CR) after LNG-IUS therapy. Secondary outcomes included the recurrence rate after CR and success rate of conception. Results: Among the 93 patients, 15 (16.1%) were classified as MMRd, 6 (6.5%) as POLEmutated, 5 (5.4%) as p53-abnormal, and 67 (72.0%) as p53 wt. Comparison of serum cancer antigen 125, family history of tumor, and positive rates of programmed cell death 1 ligand 1 protein and Ki67 protein in 4 groups showed statistically significant differences (p<0.05).Patients with the p53-abnormal subtype had the lowest overall CR rate (40%) and the highest recurrence rate (2/2). Patients with POLE-mutated subtype had the best prognosis, and all 6 patients achieved CR. When patients achieved complete remission, assisted reproductive technology was more likely to help them conceive than natural conception (p<0.05). Conclusion Patients with early-stage EC or AEH who are more likely to benefit from fertilitysparing treatment can be identified using ProMisE classifier. Patients with POLE-mutated are suitable for fertility-sparing treatment with LNG-IUS.

Objective To explore the levels of interleukin-37(IL-37)and CC type modified chemokine 11(CCL11)in serum of pregnant women infected with group B streptococcus in late pregnancy and their predic-tive efficacy for maternal and infant outcomes.Methods A total of 86 pregnant women with reproductive tract B streptococcus infection in late pregnancy treated in the hospital from December 2020 to December 2022 were selected as the study group,and 76 pregnant women with normal physical examination admitted during the same period were selected as the control group.The levels of IL-37 and CCL11 in serum of all pregnant women were detected by enzyme-linked immunosorbent assay.According to whether the pregnant women with group B streptococcus infection in late pregnancy had adverse maternal and infant outcomes,they were divided into normal pregnancy outcome group(50 cases)and adverse pregnancy outcome group(36 cases).Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of serum IL-37 and CCL11 on maternal and infant outcomes of pregnant women with reproductive group B streptococcus infection in late pregnancy.Multivariate Logistic regression was used to analyze the factors affecting maternal and in-fant outcomes of pregnant women with reproductive group B streptococcus infection in late pregnancy.Results The levels of IL-37 and CCL11 in the study group were higher than those in the control group(P<0.05).The incidence rate of adverse outcomes in the study group was significantly higher than that in the control group(P<0.05).The proportion of abortion history and the proportion of vaginal microecological disorders and levels of IL-37 and CCL11 and in adverse pregnancy outcome group were higher than those in normal pregnancy outcome group(P<0.05).ROC curve results showed that the area under the curve(AUC)of IL-37 and CCL11 for predicting adverse maternal and infant outcomes of pregnant women infected with group B streptococcus in late pregnancy were 0.876(95%CI:0.824-0.920)and 0.788(95%CI:0.748-0.830),re-spectively.The AUC of the combined prediction of adverse maternal and infant outcomes of pregnant women infected with group B streptococcus were 0.927(95%CI:0.889-0.970).Multivariate Logistic regression a-nalysis results showed that serum IL-37(OR=3.604,95%CI:2.106-6.166),CCL11(OR=4.250,95%CI:2.074-8.709),abortion history(OR=2.707,95%CI:1.688-4.342)and vaginal microecological disorders(OR=3.504,95%CI:1.993-6.162)were risk factors for adverse maternal and infant outcomes in pregnant women infected with group B streptococcus in late pregnancy(P<0.05).Conclusion The levels of IL-37 and CCL11 in serum of pregnant women infected with reproductive group B streptococcus in late pregnancy are in-creased,which are related to adverse pregnancy outcomes,and are expected to be effective indicator for predic-ting adverse pregnancy outcomes of pregnant women infected with reproductive group B streptococcus in late pregnancy.

Objective To evaluate the mechanism of governor vessel electroacupuncture in rats with post-stroke limb spasm by observing the changes of glutathione antioxidant system-related factors.Methods A total of 60 SD rats were randomly divided into the normal group(n=12),sham operation group(n=12)and modeling group(n=36).The middle cerebral artery obstruction model was prepared by thread approach method in the modeling group,and 24 rats with successful modeling were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.At the 3rd day after modeling,the electroacupuncture group was treated with electroacupuncture at three acupoints of the governor vessel,namely,"Dazhui"(GV14),"Jizhong"(GV6)and"Houhui"(anteromedial of the transverse process of the sixth lumbar vertebra),for 30 min each time,once a day for 7 days.The neurological function of rats was assessed by Zea Longa neurological deficit score.The muscle tension of rats was detected by modified Ashworth dystonia rating and electrophysiological tracing method.The brain tissue water content was measured by the dry-wet weight method.The volume of cerebral infarction of rats was measured by the TTC staining method.The contents of glutathione(GSH),catalase(CAT),oxidized glutathione(GSSG),superoxide dismutase(SOD),and malondialdehyde(MDA)in the cortex of rats were detected by colorimetry.The protein and mRNA expressions of glutathione reductase(GR),glutamate cysteine ligase(GCL)C,GCLM,and glutathione peroxidase 4(GPX4)in the cortex of rats were measured by Western blotting and real-time PCR,respectively.Results Compared with rats in the normal and sham operation groups,the Zea Longa neurological deficit score,modified Ashworth dystonia rating,the volume of cerebral infarction,brain tissue water content,and GSSG and MDA contents in cortex were increased in the model group,the tension signal value and the proteins and mRNA expressions of GR,GCLC,GCLM,and GPX4 in cortex were decreased,and the contents of GSH,CAT,and SOD in cortex were decreased(P＜0.05).Compared with the model group,the Zea Longa neurological deficit score,modified Ashworth dystonia rating,the volume of cerebral infarction,brain tissue water content,and GSSG and MDA contents in cortex were decreased in the electroacupuncture group,the tension signal value and the proteins and mRNA expressions of GR,GCLC,GCLM,and GPX4 in cortex were increased,and the contents of GSH,CAT,and SOD in cortex were increased(P＜0.05).Conclusion Governor vessel electroacupuncture can improve the severity of post-stroke limb spasm in rats,and its mechanism may be related to the regulation of glutathione antioxidant system in cerebral cortex.

Objective: To determine whether proactive molecular risk classifier for endometrial cancer (ProMisE) could be used to assess the prognosis of patients with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC) treated with levonorgestrelreleasing intrauterine system (LNG-IUS). Methods: A retrospective cohort study was conducted among 93 AEH or early-stage EC patients who received LNG-IUS to preserve fertility . By immunohistochemistry and gene sequencing, 4 subtypes of ProMisE were identified (p53 wild type [p53 wt], mismatch repairdeficient [MMRd], p53-abnormal, and POLE-mutated). The primary outcome was the time to complete response (CR) after LNG-IUS therapy. Secondary outcomes included the recurrence rate after CR and success rate of conception. Results: Among the 93 patients, 15 (16.1%) were classified as MMRd, 6 (6.5%) as POLEmutated, 5 (5.4%) as p53-abnormal, and 67 (72.0%) as p53 wt. Comparison of serum cancer antigen 125, family history of tumor, and positive rates of programmed cell death 1 ligand 1 protein and Ki67 protein in 4 groups showed statistically significant differences (p<0.05).Patients with the p53-abnormal subtype had the lowest overall CR rate (40%) and the highest recurrence rate (2/2). Patients with POLE-mutated subtype had the best prognosis, and all 6 patients achieved CR. When patients achieved complete remission, assisted reproductive technology was more likely to help them conceive than natural conception (p<0.05). Conclusion Patients with early-stage EC or AEH who are more likely to benefit from fertilitysparing treatment can be identified using ProMisE classifier. Patients with POLE-mutated are suitable for fertility-sparing treatment with LNG-IUS.

Objective: To determine whether proactive molecular risk classifier for endometrial cancer (ProMisE) could be used to assess the prognosis of patients with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC) treated with levonorgestrelreleasing intrauterine system (LNG-IUS). Methods: A retrospective cohort study was conducted among 93 AEH or early-stage EC patients who received LNG-IUS to preserve fertility . By immunohistochemistry and gene sequencing, 4 subtypes of ProMisE were identified (p53 wild type [p53 wt], mismatch repairdeficient [MMRd], p53-abnormal, and POLE-mutated). The primary outcome was the time to complete response (CR) after LNG-IUS therapy. Secondary outcomes included the recurrence rate after CR and success rate of conception. Results: Among the 93 patients, 15 (16.1%) were classified as MMRd, 6 (6.5%) as POLEmutated, 5 (5.4%) as p53-abnormal, and 67 (72.0%) as p53 wt. Comparison of serum cancer antigen 125, family history of tumor, and positive rates of programmed cell death 1 ligand 1 protein and Ki67 protein in 4 groups showed statistically significant differences (p<0.05).Patients with the p53-abnormal subtype had the lowest overall CR rate (40%) and the highest recurrence rate (2/2). Patients with POLE-mutated subtype had the best prognosis, and all 6 patients achieved CR. When patients achieved complete remission, assisted reproductive technology was more likely to help them conceive than natural conception (p<0.05). Conclusion Patients with early-stage EC or AEH who are more likely to benefit from fertilitysparing treatment can be identified using ProMisE classifier. Patients with POLE-mutated are suitable for fertility-sparing treatment with LNG-IUS.

Objective:To investigate the significance of MLH1 protein expression and MLH1 gene methylation rate between metastatic solid pseudopapillary tumor of pancreas (SPT) and non-metastatic SPT, and to explore the correlation between MLH1 gene methylation and SPT metastasis.Methods:Twelve metastatic SPT patients admitted to Peking University People's Hospital, Rizhao Central Hospital and Chaoyang Central Hospital of Liaoning Province from January 2009 to May 2022 were studied retrospectively, including 3 males and 9 females, with a median age of 47 years old, ranging from 21 to 73 years old. Thirty non-metastatic SPT patients with clear diagnosis, clear medical history and complete follow-up data from pathological database of Peking University People's Hospital from January 2009 to May 2017 were selected as the control group, including 12 males and 18 females, with a median age of 42 years old, ranging from 34 to 69 years old. Clinical data such as gender, age and pathological data were collected. Immunohistochemical expression of MLH1 protein and methylation of MLH1 gene were detected by pathological paraffins.Results:There was no significant difference in general data between the two groups (all P>0.05). Among the 12 metastatic SPT patients, 4 cases metastasized to liver, 2 to spleen, 2 to lung, 2 to lymph nodes, 1 to mediastinum, and 1 to sacrum. Compared with the non-metastatic tissue, the MLH1 protein deletion in metastatic pancreatic lesions (metastatic SPT-P) and metastatic lesions (metastatic SPT-M) were increased [both 33.3%(4/12)], and the difference was statistically significant (both Chi square=5.00, both P=0.041). Compared with 0 (0/30) MLH1 gene methylation rate in non-metastatic SPT tissues, the methylation rate of MLH1 gene in metastatic SPT-M and metastatic SPT-P tissues [both 30% (3/10)] were higher, with statistical significance (both Chi square=0.96, both P=0.032). Conclusion:Compared with non-metastatic SPT, the loss rate of MLH1 protein expression and MLH1 gene methylation are increased in metastatic SPT. MLH1 methylation may occur before metastasis, which can be used as a predictor of SPT metastasis.

Objective:To explore the influencing factors of long-term survival for hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA).Methods:A retrospective analysis of 255 patients who underwent RFA as the main treatment modality for HCC from May 1, 2004 to Feb 28, 2015 was performed. All patients were divided into two groups according to the postoperative survival time: the 5-year or more survival group and the less than 5-year survival group. Clinical indicators such as age, maximum tumor size and number, and frequency of radiofrequency ablation were compared between the two groups. Cox single factor and multiple factors were used to analyze the influencing factors of long-term survival.Results:The median overall survival of all the 255 patients was 4.3 years (range 0.5-15.5 years). There were 115 patients (45.1%) who survived for 5 years or more and 140 patients (54.9%) who survived for less than 5 years. The 1-, 3-, 5-, and 10-year survival rates of all the patients were 86.7%, 61.2%, 44.8% and 34.8%, respectively. There were no significant differences in gender, age, accompanying symptoms, aetiology of liver disease, level of alpha fetoprotein and treatment ( P>0.05), but there were significant differences in Child-Pugh class, liver cirrhosis, maximum diameter of tumor, tumor number, tumor stage, and frequency of RFA ( P<0.05) between the 2 groups of patients. Multivariate analysis showed that age ≥70 years old, Child-Pugh class B, maximum diameter of tumor >5.0 cm, multiple tumor were independent risk factors of long-term survival, but the number of sessions of RFA was a protective factor. Conclusions:For medium sized HCC and solitary large HCC, RFA combined with other therapeutic modalities could achieve satisfactory therapeutic results. Age, Child-Pugh class, maximum diameter of tumor, tumor number and RFA frequency were influencing factors for long-term survival of HCC patients.

Seventy two patients with initial cerebral infarction admitted in the Second Hospital of Jiaxing from March 2017 to October 2017 were enrolled. Patients underwent conventional ultrasonography and contrast-enhanced ultrasonography for two-dimensional echo grading and neovascularization grading of carotid artery plaques respectively. There were 113 carotid plaques in 72 patients with cerebral infarction,27 cases recurred after 1 years with 44 patches. The echo grading of recurrence group was mainly grade Ⅰ and grade Ⅱ,the number of Ⅰ,Ⅱ,and Ⅲ plaques was 23,18,and 3,respectively. The echo grading of non-recurrence group was mainly grade Ⅲ,the number of Ⅰ,Ⅱ,and Ⅲ plaques was 36,23,and 40,respectively. The echo grading of carotid artery plaque between the two groups was significantly different (P<0.05). The grade of carotid neovascularization in recurrence group was mainly grade Ⅲ and grade Ⅳ,the number of Ⅰ,Ⅱ,Ⅲ and Ⅳ plaques was 2,5,27 and 10,respectively. The echo grading of non-recurrence group was mainly grade Ⅰ and grade Ⅱ,the number of Ⅰ,Ⅱ,Ⅲ and Ⅳ plaques was 24,52,14 and 9,respectively. There was significant difference in the grade of carotid neovascularization between the two groups (P<0.05). The area under curve(AUC) of echo grade<Ⅱ,echo grade<Ⅲ,neovascularization grade>Ⅰ,neovascularization grade>Ⅱ and neovascularization grade>Ⅲ in predicting the recurrence of cerebral infarction were 0.553,0.641,0.587,0.793 and 0.557,respectively,the AUC of neovascularization grade>Ⅱ was significantly higher than the other four criteria (P<0.01). The recurrence curves of carotid plaques with different neovascularization grades were significantly different (χ²=49.18,P<0.01). Carotid plaque vulnerability evaluated by contrast-enhanced ultrasonography is an effective indicator for predicting recurrence of cerebral infarction.

OBJECTIVETo study the risk factor of perioperative complication in gastric cancer patients with radical therapy and its influence on prognosis.

METHODSClinical, pathological and follow-up data of 1 148 gastric cancer patients undergoing radical gastrectomy at Tianjin Medical University Affiliated Tumor Hospital between January 2009 and August 2011 were retrospectively collected. Pearson 2 test and Logistic regression analysis were used to analyze the risk factor of perioperative complication. Cox regression analysis was used to evaluate the influence of perioperative complications on the prognosis in patients after radical gastrectomy. Kaplan-Meier survival curve was applied to calculate the survival.

RESULTSOf 1 148 patients, 851 were male, 297 were female, age ranged from 19 to 89 (average 59.9) years. Perioperative complication occurred in 312 cases (27.2%), including 140 cases of pulmonary infection and 53 cases of abdominal infection. Multivariate Logistic regression analysis showed that ≥65 years old (OR:0.736, 95%CI: 0.558 to 0.971, P=0.030), serum albumin less than 35 g/L(OR:2.626, 95%CI: 1.479 to 4.665, P=0.001), Borrmann type IIII((OR: 0.748, 95%CI: 0.610 to 0.917, P=0.005), tumor site at upper 1/3 of stomach (OR:1.326, 95%CI:1.167 to 1.506, P=0.000), combined organ resection(OR:0.624, 95%CI:0.428 to 0.909, P=0.014) were independent risk factors of perioperative complication. Tumor site at upper 1/3 of stomach (OR:1.649, 95%CI: 1.368 to 1.988, P=0.000), ≥65 years old (OR:0.548, 95%CI:0.379 to 0.792, P=0.001), without intraoperative chemotherapy (OR:1.671, 95%CI:1.146 to 2.437, P=0.008) were independent risk factors of perioperative pulmonary infection; Borrmann type IIII((OR:0.576, 95%CI:0.369 to 0.900, P=0.015), with intraoperative chemotherapy (OR:0.431, 95%CI:0.230 to 0.810, P=0.009), intraoperative blood loss ≥400 ml(OR:0.411, 95%CI:0.176 to 0.959, P=0.040) and combined organ resection (OR:0.412, 95%CI:0.215 to 0.789, P=0.008) were independent risk factors of perioperative intraperitoneal infection. Cox regression analysis revealed that without intraoperative chemotherapy, proximal subtotal or total gastrectomy, TNM stage III(, N3 stage lymph node metastasis, positive soft tissue outside lymph node, combined organ resection and organ failure were independent risk factors affecting the prognosis of gastric cancer patients after radical resection (all P<0.05), however the perioperative complication was not independent risk factor affecting the prognosis (P=0.259). The median survival time was 35 months, and 5-year survival rate was around 38.7%. The median survival time of gastric cancer patients with operative complications and without complications were 28.0 and 36.5 months, and the 5-year survival rates were 37.2% and 39.3%, whose difference was not statistically significant (P=0.259).

CONCLUSIONThere is a higher risk of perioperative complication in those gastric cancer patients with old age, preoperative low serum albumin level, tumor site at upper 1/3 of stomach, Borrmann type IIII(, intraoperative combined organ resection, while the perioperative complication has no significant effects on the long-term survival.