BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

This study intends to establish a colorectal cancer(CRC)organoid model,expand and isolate CRC-reactive tumor-infiltrating lymphocytes(TILs),screen tumor-specific T cell receptors(TCRs)and perform functional verification,in order to provide a technological platform and research foundation for the clinical transformation of individualized adoptive T-cell immunotherapy for colorectal cancer.An organoid model derived from colon cancer patient tissues was constructed using in vitro 3D culture techniques,which then subjected to HE staining and immunohistochemistry for detecting morphological characteristics and representative molecular expression.Subsequently,CRC organoids were co-cultured with TILs for sorting reactive TILs using flow cytometry,and the characteristics of reactive TCR clones was analyzed through single T cell receptor gene cloning technology.Furthermore,the function of TCRs was verified through cytotoxicity experiments.Morphological analysis and representative molecules(CK20 and CDX2)expression indicated that there is high similarity between colorectal cancer organoids and patient tumors.In the in vitro expanded and cultured TILs,colorectal cancer-reactive T cells with upregulated CD137 expression and increased IFN-γ secretion were screened out successfully,among which TCR2-T cells demonstrated superior tumor reactivity and in vitro tumor killing function.In conclusion,a platform for screening and function validation of reactive TCRs based on CRC-Org has been established,providing a technological platform for the translational application of individualized T-cell therapy for colorectal cancer.

Objective To investigate the predictive value of serum Nesfatin-1 and 25-hydroxyvitamin D3[25(OH)D3]levels for the short-term prognosis of status epilepticus(SE)in children.Methods A total of 104 children with SE admitted to the hospital from March 2020 to March 2023 were enrolled in the study,and the clinical data of the children were collected.According to the Glasgow outcome Scale(GOS)score at dis-charge,the children were divided into a good prognosis group(equal to 5 points)and a poor prognosis group(＜5 points).Univariate analysis and multivariate Logistic regression were used to analyze whether serum Nesfatin-1 and 25(OH)D3 levels were risk factors for poor short-term prognosis in children with SE.The re-ceiver operating characteristic(ROC)curve was drawn to analyze the predictive value of serum Nesfatin-1 and 25(OH)D3 levels for the short-term poor prognosis in children with SE.Results At discharge,85 children[81.73％(85/104)]with a GOS score of 5 were included in the good prognosis group,and 19 children[8.27％(19/104)]with a GOS score of＜5 were included in the poor prognosis group.There was no significant differ-ence in gender,age,previous history of epilepsy,and seizure types between the two groups(P＞0.05).There were significant differences in the duration of SE,the time from medication to seizure cessation,electroenceph-alogram(EEG)results,head CT results,and serum Nesfatin-1 and 25(OH)D3 levels between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that SE duration＞60 min,abnormal head CT results,serum Nesfatin-1 and 25(OH)D3 levels were independent risk factors for the short-term poor progno-sis of children with SE(OR=1.945,2.343,1.731,1.505;P＜0.05).The area under the ROC curve of serum Nesfatin-1 and 25(OH)D3 levels combined to predict poor short-term prognosis of children with SE was 0.840(95％CI:0.732-0.949),which was better than that of serum Nesfatin-1 and 25(OH)D3 levels alone[0.607(95％CI:0.453-0.761),0.742(95％CI:0.604-0.880)],respectively.Conclusion Serum Nesfatin-1 and 25(OH)D3 levels are risk factors for poor prognosis in children with SE,and the combination of them has high predictive value for poor prognosis in children with SE.

Objective:To compare the short-term effect of the arthroscopic reconstruction of anterior cruciate ligament (ACL) by femoral tunnel positioning through the tendon incision (TI) technique and anteromedial (AM) technique.Methods:Between December 2015 and March 2017, 176 patients with ACL injuries underwent arthroscopic ACL reconstruction at the First Affiliated Hospital of USTC were analyzed. According to the method of localization of femoral tunnel, they were divided into two groups: TI group (localization of femoral tunnel by TI for reconstruction of ACL) and AM group (localization of femoral tunnel by AM for reconstruction of ACL). There were 87 patients in the TI group (63 males and 24 females) with an age of 32.8±9.4 years (range, 19-51 years) and a body mass index (BMI) of 24.8±6.3 kg/m 2 (range, 18.1-31.7 kg/m 2), including 9 obese patients (BMI>28 kg/m 2). There were 89 patients in the AM group (59 males and 30 females) with an age of 36.7±13.0 years (range, 17-56 years) and a BMI of 25.7±5.8 kg/m 2 (range, 18.9-31.6 kg/m 2), including 11 obese patients. To evaluate whether the drill was in contact with the articular surface of the medial condyle of the femur, whether the anterior angle of the medial meniscus was damaged, the sagittal and coronal angles of the femoral tunnel and the total length of the femoral tunnel. The anterior drawer test, Lachmann test, pivot shift test, knee flexion angle (KFA), Lysholm score, International Knee Documentation Committee (IKDC) score and the incidence of postoperative complications were compared between the two groups. At the same time, the time of taking out tendon, operation time, hospital stay and recovery time were compared between two groups of obese people. Results:In the TI group, the guide pin could reach all areas of the medial wall of the lateral femoral condyle from the inferior cartilage edge to the top of the intercondylar fossa, the drill bit had no contact with the medial femoral condyle (MFC), and the anterior angle of the medial meniscus was not damaged. In AM Group, 3 cases of MFC and 1 case of anterior horn of medial meniscus were injured in order to get the best position of femoral tunnel. The angle of femoral tunnel in sagittal plane (50.2°±3.2°) and coronal plane (46.1°±5.8°) in experimental group was notably larger than that in control group (45.6°±5.4°, 38.3°±4.7°), the difference was statistically significant ( P<0.05). However, there was no significant difference in the length of femoral tunnel between the two groups (38.2±3.2 mm and 37.7±2.5 mm, P>0.05). All patients were followed up for an average of 8.3±2.1 (range, 3-12) months. The positive rates of anterior drawer test, Lachmann test and pivot shift test were not significantly different between the two groups at 3, 6, 9 and 12 months after operation ( P>0.05). The KFA, Lysholm and IKDC scores in both groups were significantly increased after operation ( P<0.05), but there was no significant difference of above indexes between the two groups ( P>0.05). The overall complication rate in AM group (14.6%, 13/89) was significantly higher than that in TI group (6.9%, 6/87), the difference was statistically significant ( P<0.05). Additionally, the tendon harvesting (15.0±0.2 min vs. 26.0±0.2 min, P<0.05) and operation time (2.0±0.3 h vs. 3.0±0.4 h, P<0.05) were significantly shortened among obese patients in experimental group compared with those in control group. Conclusion:The TI technique demonstrates comparable effectiveness to the AM technique in ACL reconstruction through femoral tunnel positioning, with the added advantage of safer femoral tunnel localization. This approach minimizes the risk of iatrogenic injuries to the articular cartilage of the medial condyle of the femur and the anterior horn of the medial meniscus. Furthermore, the TI technique reduces tendon removal time, particularly beneficial for obese patients.

Renal interstitial fibrosis （RIF） is the main pathological feature of chronic kidney disease caused by a variety of factors. "Kidney deficiency and blood stasis in collateral， miniature mass of renal collateral" is the main pathogenesis of RIF. The deficiency of healthy Qi will influence the kidney Qi， resulting in kidney deficiency and unsmooth qi transformation. As a result， phlegm， heat， stasis， toxin and other excess pathogens block the kidney collaterals， forming miniature masses. The masses accumulate in the renal collaterals， finally leading to RIF. Autophagy is a key process that keeps your body's cells in proper balance by taking aged or damaged components in a cell and recycling them. It is involved in the occurrence and development of RIF. The metabolism of excess pathogens such as phlegm， heat， stasis， and toxin in vivo is related to the degradation and reabsorption of autophagy. Autophagy is a way to eliminate phlegm， heat， stasis， toxin and other excess pathogens. Autophagy dysfunction will cause the accumulation of phlegm， heat， blood stasis， toxin and other excess pathogens， further the stasis of the kidney collaterals， miniature mass in kidney， and finally RIF. Kidney deficiency and blood stasis in collateral are the root cause of autophagy dysfunction， and the miniature mass of renal collateral is the manifestation of autophagy dysfunction. Autophagy dysfunction and miniature mass of renal collateral have the same pathological evolution. In this paper， based on the pathogenesis of "kidney deficiency and blood stasis in collateral， miniature mass of renal collateral" of RIF and RIF-autophagy relationship， this paper discusses the "kidney deficiency and blood stasis in collateral-autophagy dysfunction-miniature mass of renal collateral" relationship in RIF and comprehensively interprets the scientific connotation of the pathogenesis of "kidney deficiency and blood stasis in collateral， miniature mass of renal collateral"， which is expected to lay a basis for explaining the role of autophagy in TCM theory and for the treatment of RIF and research on the mechanism.

Objective:To investigate the application effect of Press-Z-track-Turn (PZT) intramuscular injection on the extravasation, local reaction, local pain after injection and patient satisfaction after Fulvestrant injection.Methods:Used a self-controlled study, 63 patients who underwent bilateral intramuscular injection of Fluvastatin in the outpatient injection room of Tianjin Medical University Cancer Hospital from August to October 2022 were conveniently selected. The observation time was two treatment cycles after inclusion in this study. Before the injection of the first treatment cycle, a coin toss was used to randomly decide to use traditional intramuscular injection and PZT intramuscular injection method for injection and record. After 28 days, another injection method was used, with a total of 126 injections per injection method. Observed the extravasation of drug solution and local reactions at the injection site within 7 days after injection using two injection methods, as well as the pain and satisfaction of patients within 7 days after injection.Results:The extravasation rate of drug solution for the PZT intramuscular injection was 1.59% (2/126), which was lower than 7.14% (9/126) for the traditional intramuscular injection, and the difference was statistically significant ( χ2=4.66, P<0.05); the incidence of mild and moderate local reactions for the PZT intramuscular injection was 3.97% (5/126) and 1.59% (2/126), respectively, lower than that for the traditional intramuscular injection 11.11% (14/126) and 5.56% (7/126), and the difference was statistically significant ( χ2=8.26, P<0.05); the pain score of the PZT intramuscular injection was (2.08 ± 0.85) points, lower than that of the traditional intramuscular injection (5.03 ± 1.06) points, and the satisfaction score of the PZT intramuscular injection was (23.68 ± 1.64) points, higher than that of the traditional intramuscular injection (20.10 ± 2.58) points. The difference was statistically significant ( t=-17.24, 9.16, both P<0.01). Conclusions:PZT intramuscular injection can effectively reduce the overflow rate, the incidence of grade 1 and 2 local reactions and the degree of pain of patients, and improve patient satisfaction, which is worthy of clinical application.

Renal interstitial fibrosis（RIF）is a common pathway for the progression of chronic kidney disease to renal failure，and its pathogenesis is mainly related to renal inflammatory damage，oxidative stress，apoptosis，and excessive extracellular matrix（ECM） deposition. Transforming growth factor-β₁（TGF-β₁） signaling pathway，mammalian target of rapamycin（mTOR） signaling pathway and other signaling pathways mediate the occurrence and development of RIF. Because of the complicated mechanism of RIF，there have been no specific prevention and treatment measures in clinical practice. Autophagy is a non-damaging response produced by eukaryotic cells. It maintains the balance of tissue homeostasis through degradation and reabsorption. At present， Chinese medicine has achieved desirable clinical effects with its unique advantages of multiple components，multiple effects，and multiple targets in the treatment of chronic kidney disease to delay the process of RIF. Scholars have found that autophagy is consistent with the Yin-Yang theory and the theory of abdominal mass in traditional Chinese medicine （TCM） to a certain extent，and it is involved in many aspects of RIF. The progression of RIF is closely related to autophagy. The targeted therapy of RIF by intervention in autophagy has become the frontier of research. However，little is known about the role of autophagy in RIF and the regulation of autophagy by Chinese medicine in the treatment of RIF. Therefore，it is necessary to further elucidate the relationship between autophagy and RIF in order to clarify the mechanism of autophagy in RIF and the mechanism of Chinese medicine regulating autophagy in targeted therapy of RIF. This article focused on the correlation between autophagy and RIF based on TCM theory，and systematically summarized the role of autophagy in RIF and the intervention of Chinese medicine by combining the effects of autophagy on inflammation damage，oxidative stress，apoptosis，and excessive ECM deposition in RIF， and the regulation mechanism of autophagy in TGF-β₁ and mTOR signaling pathways in RIF. This study was expected to provide a certain reference for the clinical treatment of RIF and the development of new drugs.

Chronic renal failure （CRF）， a common outcome of various chronic kidney diseases， is characterized by retention of metabolites and toxins， water-electrolyte imbalance， acid-base disturbance， and various symptoms in diverse systems. The incidence and progression of this disease are influenced by many factors， particularly the change of intestinal flora. Previous research shows that the intestinal flora interacts with CRF. For CRF patients， the metabolic waste fails to be cleared in time due to the gradual decline of renal function and thus accumulates in vivo. Moreover， CRF changes the composition of intestinal flora， damages intestinal barrier， and accelerates the synthesis of intestinal uremic toxins and the accumulation in blood. As a result， the renal injury is aggravated. The imbalance of intestinal flora can induce acute kidney injury， increase cardiovascular complications， stimulate immune inflammatory responses， and thus aggravate the progression of CRF. Microbiota-targeted therapy for CRF has become the research focus. According to traditional Chinese medicine， kidney disease is related to the intestine and kidney disease should be treated from the intestine. Spleen and kidney are in the closest relationship with the pathogenesis of CRF and the intestinal flora. Chinese medicine， which features multiple targets， multiple effects， and multiple components， acts on the "gut-kidney axis". It is thus superior in the clinical treatment of CRF and the regulation of intestinal flora. To be specific， it intervenes in intestinal flora to delay the process of CRF. In this paper， based on the correlation of traditional Chinese medicine theory with intestinal flora and CRF， this paper reviewed the interaction between intestinal flora and CRF and traditional Chinese medicine intervention in the intestinal flora for the treatment of CRF， which is expected to serve as a reference for the clinical treatment of this disease and the drug development.

Objective:To explore the effect of multiple intelligences theory combined with the analysis, design, development, implementation, and evaluation (ADDIE) model in surgical clinical practice teaching.Methods:A total of 100 residents trained in Department of Gastrointestinal Surgery of Heping Hospital Affiliated to Changzhi Medical College from July 2019 to April 2020 were randomly divided into the control group ( n=50) and the observation group ( n=50). The control group used the ADDIE model, and the observation group adopted the multiple intelligences theory combined with the ADDIE model. The teaching assessment of the two groups was compared, and the core competence, critical thinking ability, self-evaluation, and teaching satisfaction of the two groups were evaluated. SPSS 22.0 was used for Chi-square test and t-test. Results:The scores of basic knowledges of gastrointestinal surgery, surgical clinical thinking and case analysis, routine skills and operations, and the total scores in the observation group were higher than those in the control group ( P<0.05). The scores of professional knowledge and skills, patient safety and rights, scientific research and academic ability, professional ethics, teamwork, personal and professional development ability in the observation group were higher than those in the control group ( P<0.05). While, there was no significant difference in the mastering of knowledge between the two groups ( P>0.05). The four dimensions of learning interest, self-learning ability, innovation ability, and clinical thinking establishment in the observation group were higher than those in the control group ( P<0.05). Conclusion:Multiple intelligences theory combined with ADDIE model in surgical clinical practice teaching can improve the teaching assessment results, significantly enhance the core competence, stimulate the learning interest, cultivate the self-learning ability and innovation ability of residents, and help them to establish clinical thinking ability.