Objective To investigate the relationship between the expression of serum cartilage intermediate layer protein 1(Cilp1)and myocardial fibrosis(MF)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 106 patients with T2DM(T2DM group)who were admitted to The First Hospital of Qinhuangdao were selected for this study,and 110 healthy individuals were entered into the control group.The serum Cilp1 and MF indexes[procollagen type Ⅲ-N-terminal peptide(P Ⅲ NP),galactose lectin-3(Gal-3),hyaluronic acid(HA),type Ⅲ procollagen(PCⅢ)]were detected and compared between the two groups.According to the degree of MF,there were 31,25,23,and 27 patients with stage 0,1,2,and 3 disease,respectively.The levels of serum Cilp1 and serum Cal-3,P Ⅲ NP,PC Ⅲ,HA were compared between patients of different stages.The Spearman method was applied to analyze the correlation between serum Cilp1 and MF staging,while the Pearson method was applied to analyze the correlation between serum Cilp1 and Gal-3,P Ⅲ NP,PC Ⅲ,HA.We also performed a multivariate logistic regression analysis of the influencing factors of MF 2 to 3 in patients with T2DM,and a receiver operating characteristic(ROC)curve analysis was applied to evaluate the diagnostic efficacy of serum Cilp1 level for MF 2 to 3 in patients with T2DM.Results The serum Cilp1 level in the T2DM group was higher than that in the control group(t=21.758,P＜0.05).Furthermore,the serum levels of Gal-3,P Ⅲ NP,PC Ⅲ,and HA in the T2DM group were higher than those in the control group(t=16.536-27.385,all P＜0.05),and the serum Cilp1 level in patients with T2DM positively correlated with MF staging,Gal-3,PⅢ NP,PC Ⅲ,and HA(r=0.724,0.555,0.501,0.588,0.655,all P＜0.05).The expression level of serum Cilp1 was found to be an influencing factor of MF 2 to 3 in patients with T2DM(P＜0.05).Furthermore,the ROC curve analysis showed that the area under the curve of serum Cilp1 for diagnosing MF stage 2 to 3 in patients with T2DM was 0.914.Conclusion Serum Cilp1 levels are elevated in patients with T2DM,and Cilp1 level closely relates to the formation of MF.This information can assist in clinical judgment of the degree of MF in patients with T2DM.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

Objective To provide a comprehensive review of the modeling method of the empty bottle stimulation(EBS)anxiety model,including commonly used experimental animal strains and genders,animal grouping,modeling procedures,modeling duration,primary behavioral evaluation method,and the underlying pathological mechanisms.This aims to offer a reference for the application of the EBS anxiety model in anxiety disorder research.Methods Searches were conducted in databases such as CNKI and PubMed to collect all literature related to the EBS anxiety model,which were then systematically summarized and organized.Results(1)Male adult SD or Wistar rats are predominantly used as experimental animals;(2)The optimal modeling period is 2 weeks;(3)Behavioral evaluations primarily utilize the open field test,elevated plus maze test,and light-dark box test;(4)Pathological mechanisms involve abnormal neurotransmitter metabolism in brain regions such as the hippocampus,prefrontal cortex,and amygdala.Conclusions The EBS anxiety model exhibits an anxiety-like behavioral phenotype and associated neurobiological mechanisms,validating its utility as an animal model for the study of anxiety disorders.However,further exploration and refinement are required for its standardized construction protocol and the understanding of its mechanistic underpinnings.

Objective To explore the mechanism of the thioredoxin-interacting protein(TXNIP)/thioredoxin-1(Trx-1)pathway in regulating the polarization of retinal microglia in rats after retinal ischemia-reperfusion(RIR)in rats,and to provide new ideas for the prevention and treatment of retinal ischemia reperfusion injury(RIRI).Methods For-ty-two healthy adult male Sprague-Dawley rats were randomly divided into a Sham group,a RIRI group and a TXNIP siRNA group.The right eye of the rats was experimented.For RIRI and TXNIP siRNA groups,RIRI models were established using the anterior chamber high intraocular pressure method.Rats in the TXNIP siRNA group were given the intravitreal injection of TXNIP siRNA 3 d before modeling.Hematoxylin-eosin(HE)staining was used to analyze retinal histopathologic changes of rats in all groups 24 h after modeling.Immunohistochemical staining of brain-specific homeobox/POU domain proteins 3A(Brn-3a)was made to count the number of retinal ganglion cells(RGCs).The dynamical changes in the number of TXNIP+cells 6 h,24 h,72 h and 7 d after modelling were analyzed through immunohistochemical staining in the RIRI group.The retinal microglia polarization and changes in the expression of TXNIP and Trx-1 proteins in each group were de-tected by double immunofluorescence staining and Western blot 24 h after modeling.Results HE staining results showed that 24 h after modelling,the retinal cells were disordered and the inner retinal layer was thickened and swelled in RIRI and TXNIP siRNA groups,compared with those in the Sham group(all P＜0.05).Immunohistochemical staining results of Brn-3a showed that 24 h after modeling,the number of Brn-3a+cells in RIRI and TXNIP siRNA groups significantly decreased,compared with that in the Sham group(both P＜0.05).The number of Brn-3a+cells in the TXNIP siRNA group was signifi-cantly higher than that in the RIRI group(P＜0.05).Immunohistochemical staining results of TXNIP at different time points after modeling showed that the expression of TXNIP+proteins started to increase 6 h after modeling.The TXNIP+protein level reached a peak at 24 h and then decreased gradually.Western blot results revealed that 24 h after modeling,RIRI and TXNIP siRNA groups had significantly higher TXNIP levels and significantly lower Trx-1 levels than the Sham group(all P＜0.05).Compared with those in the RIRI group,the expression of TXNIP proteins was significantly lower and the expression of Trx-1 proteins was significantly higher in the TXNIP siRNA group(both P＜0.05).Double immunofluores-cence staining showed that 24 h after modeling,Iba1+/CD206+cells were significantly more and Iba1+/CD16+cells were significantly less in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).RIRI and TXNIP siRNA groups had significantly more Ibal+/TXNIP+cells and significantly less Iba1+/Trx-1+cells than the Sham group(both P＜0.05).The number of Iba1+/TXNIP+cells was significantly lower and the number of Iba1+/Trx-1+cells was significantly higher in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).Conclusion RIR activates the TXNIP/Trx-1 path-way to induce the activation of retinal microglia and regulate the polarization of microglia,thereby resulting in RIRI in rats.

[Objective]To analyze the thought of Professor HE Ruoping in applying Xiaoyao Powder,in order to expand the clinical application of Xiaoyao Powder,and improve the ability of clinical syndrome differentiation and prescription selection.[Methods]Through daily consultations with teachers,collecting medical cases and literature retrieval,this paper discusses the new interpretation of the modification of Xiaoyao Powder.It also presents typical medical cases treated with this formula for conditions such as menstrual disorders,anxiety disorders,ovarian cysts and human papillomavirus(HPV)infection.Furthermore,it summarizes Professor HE's clinical experience in applying Xiaoyao Powder.[Results]Professor HE suggests modifying the original Xiaoyao Powder by removing Mentha haplocalyx Briq.,replacing Zingiber officinale Rosc.with Zingiber officinale Rosc.(dried)to enhance the formula's ability to warm the middle and disperse cold.Additionally,she adds Paeonia suffruticosa Andr.to invigorate blood and dispel blood stasis,thus strengthening the formula's overall effect of promoting blood circulation and tonifying the spleen.Cases treated with Xiaoyao Powder as the base formula such as menstrual disorders,anxiety,ovarian cysts and HPV infections shared the common pathogenesis of liver Qi stagnation and spleen deficiency.By combining differentiation of syndromes with appropriate treatment methods,including regulating and harmonizing Qi and blood,clearing and draining heat and blood stasis,resolving masses and transforming blood stasis,and clearing heat and draining dampness,good therapeutic results were achieved.[Conclusion]Professor HE's clinical application of Xiaoyao Powder often removes Mentha haplocalyx Briq.,and uses Zingiber officinale Rosc.(dried)instead of Zingiber officinale Rosc.added with Paeonia suffruticosa Andr.She believes that this formula can be used for gynecological,psychiatric and other diseases that belong to liver depression and spleen deficiency.Different diseases can be treated with the same formula,expanding the scope of treatment and fully reflecting the role of syndrome differentiation and treatment.It is worth promoting and learning from.

OBJECTIVE To observe the effect of Jiangqi Pingxiao Formula on airway inflammation in mice with acute asthma and explore its possible mechanism.METHODS A total of 36 BALB/c mice were randomly divided into normal group,model group,dexamethasone group,low-dose,medium-dose and high-dose groups of Jiangqi Pingxiao Formula,with 6 mice in each group.Except for the normal group,the other groups were given ovalbumin to establish the acute asthma attack mouse model.The normal group and the model group were given distilled water by gavage,and the Jiangqi Pingxiao Formula groups were given Jiangqi Pingxiao Formula by gavage at the corresponding dose,once a day,for 5 consecutive days.Whole Body Plethysmography was used to measure the changes of enhanced respiratory interval(Pehn)of bronchial contraction parameters in mice.HE staining was used to observe the pathological changes of lung tissue in mice.ELISA method was adopted to detect the expression levels of interleukin 1β(IL-1β),interleukin 18(IL-18)and tumor necrosis factor α(TNF-α)in lung tissue homogenate of mice.Immunohistochemistry method was used to detect the expression level of NOD-like receptor pyrin domain-associated protein 3(NLRP3)in lung tissue of mice.Western blot method was employed to detect the expression of NLRP3 inflammasome activation-associated protein κ gene binding nuclear factor-κB(NF-κB),NOD-like receptor pyrin domain-associated protein 3(NLRP3),NIMA-associated kinase 7(NEK7),Caspase 1(Cleaved-Caspase 1)and apoptosis-associated speck-like protein(ASC)in lung tissue of mice.RESULTS Compared with the normal group,the Penh level of mice in the model group was increased(P<0.001),and the pathological results of lung tissue showed that the number of inflammatory cells around the airway increased,the inflammatory score increased(P<0.001),the expression of IL-1β,IL-18,and TNF-α in lung tissue homogenate increased(P<0.001),and the expression of NF-κB,NLRP3,NEK7,Cleaved-Caspase 1,and ASC proteins in lung tissue increased(P<0.05,P<0.01,P<0.001).Compared with the model group,the Penh level of mice in the Jiangqi Pingxiao Formula groups and the dexamethasone group was reduced(P<0.05,P<0.001),the number of inflammatory cells in lung tissue decreased,and the inflammatory score decreased(P<0.001);the expression of IL-1β,IL-18,and TNF-α in lung tissue homogenate decreased(P<0.05,P<0.01,P<0.001);the expression of NF-κB,NLRP3,NEK7,Cleaved-Caspase 1,and ASC pro-teins in lung tissue decreased(P<0.05,P<0.01,P<0.001).CONCLUSION Jiangqi Pingxiao Formula can improve lung function and airway inflammation in asthma model mice,and its mechanism may be related to regulating NLRP3 inflammasome-mediated IL-1β secretion.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Objective To provide a comprehensive review of the modeling method of the empty bottle stimulation(EBS)anxiety model,including commonly used experimental animal strains and genders,animal grouping,modeling procedures,modeling duration,primary behavioral evaluation method,and the underlying pathological mechanisms.This aims to offer a reference for the application of the EBS anxiety model in anxiety disorder research.Methods Searches were conducted in databases such as CNKI and PubMed to collect all literature related to the EBS anxiety model,which were then systematically summarized and organized.Results(1)Male adult SD or Wistar rats are predominantly used as experimental animals;(2)The optimal modeling period is 2 weeks;(3)Behavioral evaluations primarily utilize the open field test,elevated plus maze test,and light-dark box test;(4)Pathological mechanisms involve abnormal neurotransmitter metabolism in brain regions such as the hippocampus,prefrontal cortex,and amygdala.Conclusions The EBS anxiety model exhibits an anxiety-like behavioral phenotype and associated neurobiological mechanisms,validating its utility as an animal model for the study of anxiety disorders.However,further exploration and refinement are required for its standardized construction protocol and the understanding of its mechanistic underpinnings.

AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

[Objective] To explore the effectiveness of applying the PDCA (Plan-Do-Check-Act) cycle to enhance the compatibility rate of five Rh blood group antigen phenotypes between donors and recipients across multiple hospital campuses. [Methods] Clinical blood transfusion data from May to July 2022 were selected. Specific improvement measures were formulated based on the survey results, and the PDCA cycle management model was implemented from August 2022. The post-intervention phase spanned from August 2022 to October 2023. The Rh phenotype compatibility rate, the detection rate of Rh system antibodies, and the proportion of Rh system antibodies among unexpected antibodies were compared between the pre-intervention phase (May to July 2022) and the post-intervention phase. [Results] After the continuous improvement with the PDCA cycle, the compatibility rate for the five Rh blood group antigen phenotypes between donors and recipients from August to October 2023 reached 81.90%, significantly higher than the 70.54% recorded during the pre-intervention phase (May to July 2022, P<0.01), and displayed a quarterly upward trend (β=0.028, P<0.05). The detection rate of Rh blood group system antibodies (β=-9.839×10^-5, P<0.05) and its proportion among all detected antibodies (β=-0.022, P<0.05) showed a quarterly decreasing trend, both demonstrating a negative correlation with the enhanced compatibility rate (r values of -0.981 and -0.911, respectively; P<0.05). [Conclusion] The implementation of targeted measures through the PDCA cycle can effectively increase the compatibility rate of five Rh blood group antigen phenotypes between donors and recipients, reduce the occurrence of unexpected Rh blood group antibodies, thereby lowering the risk of transfusion and enhancing the quality and safety of medical care.