ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

Epidermal growth factor receptor-tyrosine kinase inhibitor （EGFR-TKI） represent a class of small-molecule targeted therapeutics for oncology treatment， and serve as first-line therapy for advanced non-small cell lung cancer （NSCLC） with EGFR- sensitive mutations， with representative agents including gefitinib， dacomitinib， and osimertinib. In clinical practice， dose adjustment of EGFR-TKI may be required for cancer patients under special circumstances such as drug combinations or hepatic/ renal impairment. Physiologically-based pharmacokinetic （PBPK） model， capable of predicting pharmacokinetic （PK） processes in humans， has emerged as a vital tool for clinical dose optimization. This article sorts the modeling methodologies， workflows， and commonly used software tools for PBPK model， and summarizes the current applications of PBPK model in EGFR-TKI precision therapy as of June 30， 2024. Findings demonstrate that PBPK modeling methods commonly employ the “bottom-up” approach and the middle-out approach. The process typically involves four steps： parameter collection， compartment selection， model validation， and model application. Commonly used software for modeling includes Simcyp， GastroPlus， and open-source software such as PK- Sim. PBPK model can be utilized for predicting drug-drug interactions of EGFR-TKI co-administered with metabolic enzyme inducers or inhibitors， acid-suppressive drugs， or traditional Chinese and Western medicines. It can also adjust dosages in conjunction with genomics， predict PK processes in special populations （such as patients with liver or kidney dysfunction， pediatric patients）， evaluate the efficacy and safety of drugs， and extrapolate PK predictions from animal models to humans.

ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but there are still many patients who suffer tumor recurrence. However, valuable predictors of treatment outcomes remain limited. This study aimed to assess the value of the serum immune biomarkers to predict the prognosis. METHODS: We reviewed cervical cancer patients treated with CCRT between January 2014 and May 2018 at Peking Union Medical College Hospital. The systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and lactate dehydrogenase (LDH) were calculated using blood samples. The relationship between immune markers and the treatment outcome was analyzed. The area under the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency. The Cox proportional hazards model and log-rank were used to predict overall survival (OS) and disease-free survival (DFS). RESULTS: This study included 667 patients. Among them, 195 (29.2%) patients were defined as treatment failure, including 127 (19.0%) patients with pelvic failure, 94 (14.1%) distant failure, and 25 (3.7%) concurrent pelvic and distant failure. It revealed that the tumor stage, size, metastatic lymph nodes (MLNs), and serum immune biomarkers, such as SII, SIRI, and LDH, were significantly related to treatment outcomes. We demonstrated that the optimal cut-off of the SII, SIRI, and LDH were 970.4 × 10 9 /L, 1.3 × 10 9 /L, and 207.52 U/L, respectively. Importantly, this study presented that LDH level had the highest OR (OR = 4.2; 95% CI [2.3-10.8]). Furthermore, the OS and DFS for patients with pre-SII ≥970.5 × 10 9 /L were significantly worse than those with pre-SII <970.5 × 10 9 /L. Similarly, pre-SIRI ≥1.25 × 10 9 /L and pre-LDH ≥207.5 U/L were related to poor survival outcomes. CONCLUSIONS This study demonstrated that the baseline SII, SIRI, and LDH levels can be used to accurately and effectively predict the treatment outcomes after CCRT and long-term prognosis. Our results may offer additional prognostic information in clinical, which helps to detect the potential recurrent metastasis in time.
Humans ; Female ; Uterine Cervical Neoplasms/drug therapy* ; Middle Aged ; Adult ; Aged ; Chemoradiotherapy/methods* ; L-Lactate Dehydrogenase/blood* ; Treatment Outcome ; Disease-Free Survival ; Prognosis ; ROC Curve ; Biomarkers, Tumor/blood* ; Proportional Hazards Models

Bacteriophages possess the ability to infect and kill bacteria and have now been applied in various oral diseases,providing new insights for the prevention and treatment of oral diseases.They are expected to become a novel biological antibacterial agent for treating oral diseases.This paper comprehensively discusses the application of bacteriophages in oral medicine from six aspects:the concept and application prospects of bacteriophages,four common infectious diseases of the oral cavity and their pathogenic bacteria,existing treatment methods,and the application and outlook of bacteriophages in these diseases.Lay a theoretical basis for the clinical implementation of phage therapy.

The preparation edge of the tooth in oral restoration has always been the hot concern for dentists,and the improper preparation edge may lead to such diseases as caries and periodontitis,and ultimately lead to the restoration failure.The application of biologically oriented preparation technique has been proven to restore good periodontal soft and hard tissue morphology,which is expected to replace the traditional dental preparation methods.This article aims to comprehensively discuss the application of biologically oriented preparation technique in veneers,full crown and implantation.

Objective To study the application value of CAD/CAM technology in the teaching of inlay manufacturing.Methods A total of 60 undergraduates interned in the Department of Stomatology,Yan'an Hospital,Kunming Medical University were randomly divided into an experimental group(n=30)and a control group(n=30).We selected appropriate clinical cases for students to prepare for mandibular molar's proximal occlusal inlays.The instructor guided the results of the first preparation in different ways,and the students made the second modification and preparation,and the assessment team scored and evaluated the five aspects of the final preparation,the shape of the preparation,the shape of the occlusal surface,the dovetail retention,and the adjacent surface.Results The scores of all detection indexes in the experimental group were higher than those in the control group(P<0.05).Conclusion The application of CAD/CAM technology in inlay manufacturing teaching can effectively improve students'clinical hands-on ability and achieve better teaching effects than traditional teaching methods.

Objective To analyze the colorectal cancer screening of community residents in Pudong New Area in Shanghai and provide reference for the promotion and strategy optimization of colorectal cancer screening programs. Methods Residents aged 50-74 years in the colorectal cancer screening project of Pudong New Area in Shanghai from 2013 to 2023 were recruited in this analysis. The situation of primary screening and colonoscopy in the community was described, and results of different age groups in primary screening and colonoscopy surveys were evaluated. Chi-square test was used to determine differences between groups. Results From 2013 to 2023, 907 030 residents were screened in Pudong New Area, of which 183 724 residents were positive, and the positive rate was 20.3%. The positive rate was the lowest in the 50-54 age group and the highest in the 70-74 age group. The positive rate was higher in men than in women. The overall colonoscopy rate was 27.1%, with the highest rates in the 50-54 age group in men and the 55-59 age group in women, respectively. The participation rate of colonoscopy increased with the increase of the year. A total of 19 094 cases of intestinal lesions were found by colonoscopy. Among these lesions, 1 147 cases were colorectal cancer, accounting for 6.0%, and the population detection rate was 126.5/100 000. In addition, 4 751 cases of precancerous lesions were found, accounting for 24.9%, and the detection rate was 523.8/100 000. Conclusion Colorectal cancer screening improves the detection rate of precancerous lesions and early cancer and is of great significance for reducing the incidence and mortality of colon cancer. Measures should be taken to optimize the screening strategy based on age differences and increase the participation rate of primary screening and colonoscopy to achieve the best effect of local colorectal cancer prevention and treatment.

BackgroundPrevious investigations have illuminated the correlation between smoking and C-reactive protein （CRP）， but previous research findings may be influenced by other confounding factors. The causal relationship of CRP in smoking-related pathological process requires further exploration. ObjectiveTo investigate the causal relationship between smoking behavior and CRP by utilizing the cumulative statistical data from existing genome-wide association studies （GWAS）， so as to provide references for formulating relevant public health policies and smoking intervention measures. MethodsThis research utilized the GWAS summary statistics for CRP and four smoking phenotypes： age of initiation of regular smoking， smoking initiation， smoking cessation and cigarettes per day-selecting independent genetic loci correlated with smoking and CRP as instrumental variables. The study employed the inverse variance weighted method （IVW） and the weighted median approach for two-sample Mendelian randomization （MR） analysis to explore the bidirectional causal relationship between smoking and CRP. The Cochran's Q test was applied to assess heterogeneity among single nucleotide polymorphisms （SNPs）. MR pleiotropy residual sum and outlier was used to detect SNP outliers. MR-Egger intercept test examined the horizontal pleiotropy of SNPs. Leave-one-out sensitivity analysis assessed the impact of individual SNP on the Mendelian randomization results. ResultsThe MR analysis revealed a bidirectional causal relationship between CRP and smoking initiation （β=0.170， P=0.01） （with smoking initiationas the exposure）， （β=0.040， P=0.001） （with CRP as the exposure）. ConclusionSmoking may lead to alterations in CRP levels， while changes in CRP levels could also influence individual's propensity to initiate smoking.