ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan （DSS） on renal injury in db/db mice and its impact on endoplasmic reticulum stress （ERS） in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week， after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease （DKD） model. The model mice were randomly divided into a model group， an irbesartan group， and three DSS treatment groups with different doses （16.77， 33.54， and 67.08 g·kg^-1·d^-1）. A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention， general conditions were observed. Serum cystatin C （Cys-C）， 24-hour urinary total protein （24 h-UTP）， 24-hour urinary microalbumin （24 h-UMA）， urinary creatinine （Ucr）， and urea nitrogen （UUN） were measured. Transmission electron microscopy （TEM） was used to observe glomerular basement membrane （GBM） and ultrastructural changes of the endoplasmic reticulum （ER） in glomerular endothelial cells. Western blot， real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78， CHOP， and related markers. ResultsCompared with the normal group， the mice in the model group showed curled posture， sluggish response， poor fur condition， increased levels of Cys-C， 24 h-UTP， 24 h-UMA， and UUN （P<0.05）， while Ucr decreased （P<0.05）. The GBM was significantly thickened， with podocyte and foot process fusion. The protein expressions of GRP78， CHOP， and ATF6 were significantly upregulated （P<0.05）， the mRNA levels of GRP78 and CHOP increased （P<0.05）， and immunohistochemistry showed an enhanced GRP78 signal （P<0.05）. After treatment， the mice exhibited improved behavior， normalized GBM and podocyte structure， improved ER morphology and markedly better biochemical indicators. Western blot， Real-time PCR， and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups （P<0.05）， suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice， possibly by regulating ERS in glomerular endothelial cells， although the underlying signaling mechanisms require further investigation.

ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.

Objective:To evaluate the mechanical stability of the bone block after LeFort Ⅰ osteotomy with maxillary advancement using absorbable plates fixed with tenon-and-mortise structures.Methods:This study developed three finite element models: one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates (Model 1); another for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates assisted by tenon-and-mortise structures (Model 2); and the last one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with titanium plates and screws (Model 3). Simulated occlusal forces were applied on the anterior and posterior teeth in each model. The displacement changes of the nasal-palatine point (NP) and posterior nasal spine point (PNS) in the finite element coordinate system were compared and analyzed. The Mises equivalent stress distributions of the metal and absorbable plates were also examined to assess the mechanical stability of the three finite element models. Clinical data from 45 patients with dentofacial deformities treated from January 2017 to January 2023 at the Stomatology Hospital of China Medical University were collected. The age of the patients was 21±3 years. Among these, 15 patients had absorbable plates for fixation, 15 had absorbable plates assisted by tenon-and-mortise structures, and 15 had titanium plates and screws fixation after maxillary advancement. All patients underwent preoperative (T0), postoperative 3 days (T1), and 6 months (T2) spiral CT scans. The CT data in DICOM format were input into digital software, which was used to calculate the distances from the NP and PNS points to the horizontal plane (HP), right sagittal plane (FZSR), and coronal plane (CP) at T1 and T2. The distances at T1 and T2 were statistically analyzed using the Wilcoxon signed-rank test with SPSS 20.0, and a P value of<0.05 was considered statistically significant.Results:The finite element analysis showed that in the absorbable plate-only fixation group, the maximum displacement of the NP point (mm) under anterior and posterior tooth force conditions were 0.6 and 0.12, respectively, and for the PNS point, the maximum displacements were 0.5 and 0.11. In the tenon-and-mortise-assisted absorbable plate fixation group, the displacement of the NP point was 0.40 and 0.02 mm, and the displacement of the PNS point was 0.5 and 0.015 mm. In the titanium plate-screw fixation group, the NP point displacement was 0.33 and 0.055 mm, and the PNS point displacement was 0.16 and 0.1 mm. The Mises equivalent stress on the absorbable plates with tenon-and-mortise structure was significantly lower than that in the absorbable plate-only fixation group, while the titanium plate experienced the highest Mises equivalent stress. The clinical data analysis showed that in the horizontal direction, the postoperative stability of the three fixation methods was similar. However, in the vertical and anterior-posterior directions, the absorbable plate-only fixation group showed significant differences in the distances of PNS-HP, PNS-CP, and NP-CP between T1 and T2 ( P=0.018, P=0.009, P=0.017), suggesting significant postoperative bone displacement. In contrast, the tenon-and-mortise-assisted absorbable plate fixation group and the titanium plate-screw fixation group showed no significant differences in displacement during surgery and postoperatively(all P>0.05), demonstrating higher stability. Conclusions:The tenon-and-mortise-assisted absorbable plate fixation provides comparable stability to titanium plate fixation in clinical results, and it is more stable than absorbable plate-only fixation. In the mechanical study, when force was applied on the anterior teeth, the stability of the tenon-and-mortise-assisted absorbable plate fixation was slightly less than that of titanium plate fixation, but when posterior teeth were used, its stability exceeded both titanium plate fixation and absorbable plate-only fixation. The tenon-and-mortise-assisted absorbable plate fixation serves as an effective alternative to titanium plate fixation after LeFort Ⅰ osteotomy.

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 investigate the association of immediate preoperative hyperglycemia (IPH) with postoperative pulmonary complications (PPCs) in patients with diabetes mellitus following video-assisted thoracoscopic partial lung surgery (VATPLS).Methods:This was a retrospective cohort study. The patients with diabetes mellitus who underwent elective VATPLS at the First Affiliated Hospital of Nanjing Medical University from January, 2018 to July, 2020 were recruited. Based on immediate preoperative blood glucose levels (fasting blood glucose within 2 h before surgery), the patients were divided into hyperglycemia group (IPH group, blood glucose concentration ≥7.8 mmol/L) and non-hyperglycemia group (non-IPH group, blood glucose concentration <7.8 mmol/L). The association of IPH with the occurrence of PPCs was analyzed using the prospensity score matching.Results:Data from 438 diabetic patients who underwent VATPLS were ultimately collected in this study. Compared with non-IPH group, the incidence of PPCs was significantly increased in IPH group ( P<0.001). After propensity score matching, 128 cases were assigned to both IPH group and non-IPH group, the risk of PPCs in IPH group was 1.33 times of that in non-IPH group (relative risk 1.33, 95% confidence interval 1.02-1.73, P=0.031). There were no interactions between age factors/preoperative glycated hemoglobin and IPH. Conclusions:IPH (fasting blood glucose within 2 h before surgery ≥7.8 mmol/L) is associated with the occurrence of PPCs to some degree in patients with diabetes mellitus undergoing VATPLS.

OBJECTIVE T o explore the value of targeted next-generation sequencing(t-NGS)in diagnosis of respir-atory tract pathogens through meta-analysis so as to provide reference for clinical application.METHODS PubMed database,Web of Science database,Wanfang database,CNKI database and Sinomed database were retrieved,and the time period of retrieval ranged from Jan.2010 to May 2024.The literatures were screened out based on the es-tablished standards.The quality was assessed by QU ADAS-2,the risk of bias graph was drawn by Revman 5.4,and the statistical analysis was performed by Stata 16.0.RESULTS A total of 9 literatures were included in the study.The result of meta-analysis showed that the heterogeneity test Q for sensitivity was 268.21,P＜0.01,I2=97.02％,with the heterogeneity test Q for specificity 210.04,P＜0.01,I2=96.19％,the combined sensitivity 0.88(95％CI:0.62 to 0.97),combined specificity 0.68(95％CI:0.41 to 0.86),combined positive likelihood ratio 2.72(95％CI:1.44 to 5.15),combined negative likelihood ratio 0.18(95％CI:0.06 to 0.53),combined diagno-sis score 2.74(95％CI:1.68 to 3.80),and combined diagnostic odds ratio 15.44(95％CI:5.34 to 44.66).The area under synthesize receiver operating characteristic(SROC)curve(AUC)was 0.85(95％CI:0.82 to 0.88).The result of Deeks funnel plot showed that P was 0.99,indicating that there was no obvious publication bias.CONCLUSIONS The sensitivity of tNGS is high in detection of the pathogens causing acute respiratory tract infection,the specificity needs to be improved,but its comprehensive ability is satisfactory.It has certain val-ue in early clinical diagnosis.

Reduced or interrupted blood flow is an important pathological and physiological process in femoral head necrosis,so understanding the blood flow of the femoral head can help better understand the progression of femoral head necrosis.With the continuous development and improvement of imaging technology,the technical methods for detecting the blood flow of the femoral head are gradually being widely applied,allowing clinical physicians to better understand the blood flow situation of patients with femoral head necrosis.However,at present,the prognosis prediction of femoral head necrosis still mainly revolves around factors such as the area and angle of femoral head necrosis.Therefore,this article explores imaging techniques covering studies such as femoral head vascular imaging or blood flow perfusion parameters,summarizes their application research progress in femoral head necrosis blood flow assessment,and aims to provide more objective basis for exploring the prevention and prognosis of femoral head necrosis from the perspective of femoral head blood flow.

As a chronic progressive lung disease with poor prognosis,the pathogenesis of idiopathic pulmonary fibrosis(IPF)has not yet been clarified,and its treatment is still being explored.Animal models are important tools for studying the pathogenesis and therapeutic effects of diseases.Based on the similarity between animal models and human of IPF in terms of disease phenotype,this paper will review the research progress of IPF animal models in terms of the fibrosis mechanism induced by drugs and environmental factors,histopathological alterations,fibrosis stage,modelling time,etc.,and describe the advantages and disadvantages of different animal models,their characteristics and application profiles.

Objective To investigate the effect of Lianpu Yin on duodenal microinflammation in rats with functional dyspepsia(FD)by regulating NLRP3 activation.Methods Wistar rats were randomly divided into blank group and model group.FD rats were reconstructed by iodoacetamide method(2%sucrose solution containing 0.1%iodoacetamide),and the model was verified.FD model rats were randomly divided into model group,Lianpu Yin group and Moxapride group by random number expression method.After a period of two weeks of administration,measurements were taken to determine the body mass,three-hour food consumption,as well as the rates of gastric emptying and intestinal propulsion.The pathological structure of duodenal tissue was observed by HE staining.The serum levels of IL-1β and IL-18 were quantified using the enzyme-linked immunosorbent assay(ELISA)method.The expression levels of NLRP3 and Caspase-1 in each group were detected by Western blot.Expression levels of NLRP3 and Caspase-1 proteins were detected by immunofluorescence.Results Compared with the blank group,body weight,food intake at 3 h,gastric emptyand intestinal propulsion rate in model group were significantly decreased(P<0.01),and inflammatory infiltration of duodenum tissue appeared in the model group.Meanwhile,the expressions of NLRP3 and Caspase-1 proteins,as well as the levels of IL-1β and IL-18 in the duodenal tissue of the model group,showed significant increasing(P<0.05).Compared with the model group,rats in the Lianpu Yin and Moxapride groups displayed significant increasing in body weight,gastric emptying rate,and intestinal propulsion rate(P<0.01).Additionally,inflammatory infiltration of duodenum tissue reduced in these groups.Furthermore,NLRP3 and Caspase-1 protein expressions,as well as IL-1β and IL-18 levels,significantly decreased in the Lianpu Yin and Moxapride groups compared to the model group(P<0.05).Conclusion Lianpu Yin can treat FD rats by inhibiting duodenal microinflammation and then restoring gastrointestinal motility,which may be related to the abnormal activation of NLRP3 inflammasome.

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.