ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

ObjectiveA mouse model of vaccinia virus Tiantan strain (VTT)-induced encephalopathy was developed using AG6 mice. MethodsVTT was amplified by infecting Vero cells at a multiplicity of infection (MOI) of 0.01, followed by concentration and titration. After 72 h of incubation, virus-containing cells were collected and subjected to concentration. The concentrated viral suspension was serially diluted (10-fold dilutions) and added to 6-well plates containing confluent Vero cell monolayers for plaque assay. The number of plaques formed in each well was counted, and the virus titer was calculated based on the dilution factor. Fourteen 5-6-week-old AG6 mice (half male and half female, housed separately by sex) were randomly divided into a control group (n=3, PBS), a low-dose group (n=6, 1×10⁵ PFU), and a high-dose group (n=5, 5×10⁵ PFU). The mice were anesthetized by isoflurane inhalation and then infected via intranasal instillation. The mental state of the mice in each group was observed daily, and the body weight and mortality were recorded. On day 13 post-infection, 2% Evans Blue (4 mL/kg body weight) was administered via tail vein injection to assess blood-brain barrier (BBB) disruption. Subsequently, brain tissue samples were collected for immunofluorescence analysis to evaluate the activation of astrocytes and microglia. ResultsThe titer of purified VTT was 1×10⁷ PFU/mL. Compared with the control group, mice in the low-dose group showed no significant change in body weight, and no lethality was observed. In contrast, mice in the high-dose group exhibited significant weight loss starting on day 5 post-infection (P<0.05), accompanied by lethality. On day 13 post-infection, no Evans Blue extravasation was detected in the brain tissues of the low-dose group, while the olfactory bulb region of the high-dose group displayed distinct blue staining, indicating disruption of the BBB. Immunofluorescence analysis revealed no significant proliferation of astrocytes and microglia in the olfactory bulb region of the low-dose group on day 13 post-infection. In contrast, marked activation of glial cells was observable in the high-dose group. ConclusionAn animal model of VTT-induced encephalopathy in AG6 mice is successfully established, characterized by BBB disruption and reactive gliosis specifically localized to the olfactory bulb region, manifested as astrocytic and microglial proliferation.

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.

Background Depressive symptoms have become a significant factor affecting the physical and mental health of the occupational population, and workers in petroleum refining enterprises face multiple stressors in their work environment. Objective To explore the impact of occupational noise exposure on depressive symptoms among workers in a petroleum refining enterprise. Methods This cross-sectional study was conducted in July 2024 using a questionnaire survey among workers of a petroleum refining enterprise in Hainan Province. Basic information of the subjects was collected. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure depressive symptoms, the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) scale was used to assess sleep quality, and the Chinese version of the Effort-Reward Imbalance (ERI) scale was used to evaluate occupational stress. Chi-square test was employed to compare the differences in reporting depressive symptoms among populations with different characteristics. Binary logistic regression models were used to analyze the impact of occupational noise exposure and other factors on depressive symptoms. Results The overall positive rate of depressive symptoms in the study population was 42.7%. The results of the multifactor analysis indicated that compared with the control group, employees in both the low-exposure and high-exposure groups had elevated odds of depressive symptoms, with OR (95%CI) of 2.244 (1.131, 4.454) and 1.970 (1.009, 3.850), respectively. This association remained robust after adjusting for potential confounders, including gender, age, work tenure, and other occupational exposures. Additionally, female [OR (95%CI)=1.483 (1.039, 2.118)], exposure to benzene, toluene, or xylene [OR (95%CI)=1.621 (1.208, 2.174)], sleep disturbance [OR (95%CI)=3.772 (2.942, 4.838)], and occupational stress [OR (95%CI)=2.018 (1.575, 2.585)] were also significantly associated with higher odds of depressive symptoms. Conclusion The positive rate of depressive symptoms is relatively high among employees in this petrochemical enterprise, and occupational noise exposure may be a risk factor for depressive symptoms.

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.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Lipocalin-2 (LCN2), a member of the human lipocalin family, has been demonstrated to be closely associated with diabetes, cardiovascular diseases, and renal disorders. Recent studies have indicated that LCN2 plays a significant regulatory role in the pathogenesis and progression of various neurological diseases by mediating pathways such as inflammation, oxidative stress, and ferroptosis. This article reviews the research advancements on the mechanism of LCN2 in neurological disorders, including cerebrovascular diseases, cognitive impairment disorders, Parkinson's disease, depression, and anxiety disorders, aiming to enhance clinical understanding.

[摘 要] 目的：评估放疗作为原位疫苗的联合治疗模式在晚期软组织肉瘤（STS）患者中的有效性和安全性。方法：回顾性分析2020年12月至2024年9月期间在南京大学医学院附属鼓楼医院肿瘤中心接受联合治疗模式的12例晚期STS患者的临床资料。12例患者均接受了联合治疗。放疗主要以大分割为主。靶向治疗：安罗替尼10例、阿帕替尼2例。免疫治疗以PD-1抗体为主。主要研究终点为疾病控制率（DCR），次要研究终点为客观有效率（ORR）及安全性。结果：接受联合治疗的12例STS患者中有0例CR，4例PR，7例SD，1例PD。ORR为33%，DCR为91.7%，其中靶病灶的DCR为100%。12例患者中，9例出现Ⅰ~Ⅱ级不良反应。最常发生的血液学不良反应是贫血（6例）、肝功能检查结果异常（3例）。最常发生的非血液学不良反应是尿蛋白（5例）、高血压（4例）、甲状腺功能异常（3例）、厌食（3例）、恶心呕吐（2例）；仅2例发生Ⅲ级血液毒性，有1例发生Ⅲ级气胸。结论：放疗作为原位疫苗的联合治疗模式在晚期STS患者中展现出较高的DCR，且未出现严重不良反应。该联合治疗模式具有良好的有效性与安全性。

OBJECTIVE To investigate the analgesic effect and potential mechanism of punicalagin on neuropathic pain （NP） rats based on the hypoxia-inducible factor-1α （HIF-1α）/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Male SD rats were randomly divided into sham operation group （18 rats） and modeling group （72 rats）. NP rat model was established by chronic constriction injury （CCI） of sciatic nerve. The successfully modeled rats were divided into NP group， 2-methoxyestradiol group （HIF-1α antagonist 10 mg/kg）， punicalagin group （300 mg/kg）， and punicalagin+dimethyloxaloglycine group （punicalagin 300 mg/kg+HIF-1α agonist 175 mg/kg）， with 18 rats in each group. Rats in each group were injected intraperitoneally and/or intragastrically with the corresponding solution or 1% dimethyl sulfoxide/normal saline， once a day， for 14 consecutive days. After the last administration， the mechanical withdrawal threshold （MWT）， thermal withdrawal latency （TWL）， the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-6 in spinal cord tissue were detected； the morphological changes in the spinal dorsal horn were observed. Apoptosis rate of spinal dorsal horn neurons， the co-localization of NLRP3/ionized calcium binding adapter molecule 1 （Iba-1） （calculated by the number of NLRP3+/Iba-1+ cells） and the protein expressions of HIF-1α， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC） and caspase-1 in spinal cord tissue were detected. RESULTS Compared with the sham operation group， neurofibril in spinal dorsal horn of rats in NP group was thickened and wound into knots， and vacuolar degeneration containing silver granules was observed； the MWT and TWL were reduced or shortened； the levels of TNF-α， IL-1β and IL-6 in spinal cord tissue， the apoptosis rate of spinal dorsal horn neurons， the number of NLRP3+/Iba-1+ cells， and protein expressions of HIF-1α， NLRP3， ASC and caspase-1 were significantly increased or up-regulated （P＜0.05）. Compared with the NP group， the above indexes were significantly improved in the 2-methoxyestradiol group and punicalagin group （P＜0.05）， while dimethyloxaloglycine could significantly reverse the improvement effect of punicalagin on the above indexes （P＜0.05）. CONCLUSIONS Punicalagin can relieve pain in NP rats， and its analgesic effect may be achieved by inhibiting HIF-1α/NLRP3 signaling pathway and blocking the activation of ma0o4e@163.com NLRP3 inflammasome in spinal dorsal horn microglia.