Diabetic kidney disease （DKD） stands as one of the most prevalent microvascular complications of diabetes，noted for its concealed onset and tendency to evolve into end-stage renal disease，profoundly impacting patients' life expectancy and quality of life. Epithelial-to-mesenchymal transition （EMT） is a central pathological process in the initiation and progression of DKD，facilitating disease advancement and renal fibrosis，thus representing a crucial focus of research into the pathological mechanisms of DKD. EMT is driven by the abnormal activation of signaling pathways，including transforming growth factor-β （TGF-β）/Smad，secreted glycoprotein/β-catenin，Notch，tumor necrosis factor-α （TNF-α）/nuclear factor-κB （NF-κB），and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR），leading to renal cellular injury and subsequently accelerating renal fibrosis and the progression of DKD. Traditional Chinese medicine （TCM），characterized by its multi-target and multi-pathway therapeutic approach，demonstrates unique advantages in addressing DKD and EMT. Recent research has shown that active ingredients in TCM，including glycosides，flavonoids，and polyphenols，as well as TCM formulas，can precisely target these relevant signaling pathways，effectively inhibiting cellular injury in DKD and intervening in the EMT process. These findings not only underscore the potential of TCM monomers and formulas in treating DKD and EMT but also pave new directions for research in this field within TCM. This paper systematically reviewed the signaling pathways associated with EMT and provided an in-depth analysis of the research achievements and underlying mechanisms of TCM monomers and formulas in treating DKD and intervening in EMT，aiming to offer new insights and directions for TCM in the treatment of DKD and research on EMT，thereby further promoting the modernization and development of TCM.

Objective To analyze the implementation effect of quality control on the homepage of inpatient medical re-cords based on the background of Disease Diagnosis Related Groups(DRG).Methods A retrospective study was conducted,including a total of 20,000 medical records from Dongguan People's Hospital from 2018 to 2022.Among them,10,000 medical records from January to December 2018,before the implementation of DRG-based quality control,were included as the control group;10,000 medical records from January to December 2022,after the implementation of DRG-based quality control,were in-cluded as the observation group.The implementation effect of quality control of hospital admission medical records among different groups based on DRG was explored.Results In the control group,there were 1,943 medical records with defects,accounting for 19.43％,which affected DRG grouping in 1,000 cases(51.47％)and did not affect DRG grouping in 943 cases(48.53％).In the observation group,there were 1,316 medical records with defects,accounting for 13.16％,among which 643 cases(48.86％)affected DRG grouping and 673 cases(51.14％)did not affect DRG grouping.The difference in the number of defective medical records between the groups was statistically significant(χ2=144.11,P<0.05).The missing rates of diagnos-tic and treatment information and cost information in the observation group were lower than those in the control group(P<0.05).The completeness and accuracy rates of diagnosis and surgical information in the observation group were higher than those in the control group(P<0.05).Conclusion The implementation of quality control of hospital admission medical records based on DRG can significantly improve the quality of medical records,increase the accuracy of diagnosis and surgical information in medi-cal records,and have higher comprehensive quality control value.It is recommended for clinical promotion and use.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

ObjectiveTo observe the clinical efficacy and safety of treating mediate-risk pure ground glass pulmonary nodules （pGGNs） based on the state theory. MethodsA prospective clinical randomized controlled trial was used. Totally 141 cases of mediate-risk pGGNs were divided into treatment group （92 cases） and control group （49 cases） according to the random table method. The treatment group was given the basic Sanjie Formula （基础散结方） orally with modification according to the identification of traditional Chinese medicine （TCM） state， 1 dose per day， 3 months as a course of treatment.Three months after the treatment patients were checked by CT. Patients who were clinically judged as cure， moderate to low risk， and turned to surgical resection do not carry out a second course of treatment，and the rest of the patients continued to complete the second courses. Patients in the control group did not receive any treatment and were only followed up periodically. Patients in both groups received a CT review 3 months and 6 months after enrolled. Comprehensive curative effect was evaluated according to the reduction rate of the area of pulmonary nodules shown in chest CT， to further explore the clinical effective difference for patients at different TCM state； the risk of malignancy index （Mayo score） was calculated by Mayo model at enrollment and 3 months and 6 months after enrolled. Adverse events were monitored continuously during the study. ResultsDuring the follow-up， 8 cases in the treatment group and 7 cases in the control group were lost. A total of 126 cases completed the whole process， including 84 cases in the treatment group and 42 cases in the control group. The total effective rates at 3 months and 6 months of the treatment group were 46.15% （30/65） and 45.71% （32/70） in the treatment group， while the total effective rates at 3 months and 6 months in the control group were 12.5% （4/32） and 10.00% （4/40）. Compared with the control group， the comprehensive curative effect of 3 months and 6 months of enrollment in treatment group was significantly better than that in corresponding control group （P＜0.01）. The pulmonary nodule area and Mayo score in the treatment group decreased after 3 and 6 months of enrollment （P＜0.01）. In contrast， there was no statistically significant difference in nodule area between pre- and post-enrollment time points in the control group （P＞0.05）， and probability of Mayo risk increased in the control group after 6 months of enrollment compared to pre-enrollment （P＜0.05）. Among the 84 patients in the treatment group， there were 15 cases of qi deficiency state， 7 cases of yin deficiency state， 5 cases of yang deficiency state， 20 cases of qi depression state， 32 cases of damp-heat state， and 5 cases of harmonious state； the difference in the distribution of the total clinical effective rate of the patients with different TCM states after treatment was statistically significant （P＜0.05）， and the total effective rate of two-by-two comparison of qi depression state was higher （13/20，65.00%） than that of the total effective rate of damp-heat state （8/32，25.00%， P＜0.00833）. There were no significant changes in blood routine， urine routine， liver function and kidney function in both groups， and no adverse events occurred. ConclusionTreating mediate-risk pGGNs based on the state theory can effectively reduce the area of pulmonary nodules and inhibit the growth of malignant risk of pulmonary nodules.

Abstract: Objective To establish a rapid detection assay based on fluorescence recombinase polymerase amplification (RPA) targeting Necator americanus eggs, and to evaluate its efficacy, providing technical support for rapid detection of Necator americanus in fecal samples. Methods The fluorescence RPA primers and probe were designed based on the cox1 gene of Necator americanus and then screened the optimal combination to develop the assay. The genomic DNA of Necator americanus eggs was diluted to 7 concentration gradients including 100 pg/µL, 10 pg/µL, 1 pg/µL, 100 fg/µL, 10 fg/µL, 1 fg/µL, 0.1 fg/µL, to determine the detection limit of the assay. The specificity of the assay was demonstrated by detected genomic DNA from Schistosoma japonicum, Ascaris lumbricoides, Clonorchis sinensis and Fasciola hepatica. A total of 44 fecal samples were collected and DNA extraction was performed, and the modified Kato-Katz method, semi-nest PCR method, and fluorescent RPA method were simultaneously used for detection to evaluate the sensitivity and specificity. Results The established fluorescence RPA assay can specifically amplify a fragment of 194 bp of the Necator americanus cox1 gene within 20 min, with a detection limit of 10 fg/µL. There was no cross-reactivity with Schistosoma japonicum, Ascaris lumbricoides, Clonorchis sinensis, Fasciola hepatica after specificity validation. In 44 fecal samples, 27 positive samples were detected by the fluorescence RPA assay, and 26 positive samples were detected by both the Kato-Katz and the semi-nested PCR. The fluorescence curve of sample number 1 was slightly higher than the negative control in the later stage of the reaction, but did not show a similar trend to the positive control, and was therefore judged to be a suspected negative sample. Compared with the Kato-Katz method and the semi-nest PCR method, The sensitivity of the fluorescent RPA method were 100.00% and the specificity were 94.44%, and the consistency of the detection results was good (Kappa=0.953>0.75). Conclusions The assay based on the fluorescence RPA is an efficient, sensitive and specific technique for detecting Necator americanus and it can be applied for surveillance and early warning of hookworm infection.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

CaMKII is essential for long-term potentiation (LTP), a process in which synaptic strength is increased following the acquisition of information. Among the four CaMKII isoforms, γCaMKII is the one that mediates the LTP of excitatory synapses onto inhibitory interneurons (LTP_E→I). However, the molecular mechanism underlying how γCaMKII mediates LTP_E→I remains unclear. Here, we show that γCaMKII is highly enriched in cultured hippocampal inhibitory interneurons and opts to be activated by higher stimulating frequencies in the 10-30 Hz range. Following stimulation, γCaMKII is translocated to the synapse and becomes co-localized with the postsynaptic protein PSD-95. Knocking down γCaMKII prevents the chemical LTP-induced phosphorylation and trafficking of AMPA receptors (AMPARs) in putative inhibitory interneurons, which are restored by overexpression of γCaMKII but not its kinase-dead form. Taken together, these data suggest that γCaMKII decodes NMDAR-mediated signaling and in turn regulates AMPARs for expressing LTP in inhibitory interneurons.
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Hippocampus/metabolism* ; Interneurons/physiology* ; Long-Term Potentiation/physiology* ; N-Methylaspartate/metabolism* ; Receptors, AMPA/physiology* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Synapses/physiology*

Objective:To evaluate the effect of positive end-expiratory pressure (PEEP) ventilation on cardiac function in patients with early left ventricular (LV) diastolic dysfunction undergoing laparoscopic radical gastrectomy.Methods:Patients who underwent laparoscopic radical gastrectomy under elective general anesthesia from July 2021 to February 2022 at the Subei People's Hospital were enrolled [age 60-75 years old, American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ, and left ventricular ejection fraction (LVEF) > 0.50]. Transthoracic echocardiography (TTE) was performed before operation, and the peak early diastolic velocity (E peak) and peak late diastolic velocity (A peak) at the mitral ostium were recorded and the E/A and E peak deceleration time (DT) were calculated. Then isovolumic relaxation time (IVRT) and early peak mitral annular diastolic velocity (e') were recorded and left ventricular E/e' (LVE/e') was calculated. According to the E/A, mitral e', LVE/e', DT, and IVRT, the patients were divided into early LV diastolic dysfunction group (E/A < 1, mitral e' < 7 cm/s, LVE/e' > 14, DT > 200 ms, and IVRT > 100 ms) and normal cardiac function group (1 < E/A < 2, 160 ms < DT < 240 ms, and 70 ms < IVRT < 90 ms), with 35 patients in each group. Both groups were received fixed 5 cmH 2O (1 cmH 2O≈0.098 kPa) PEEP 5 minutes after the beginning of the pneumoperitoneum until the end of the procedure. A volume controlled ventilation was used with a tidal volume (VT) of 7 ml/kg, an inspired oxygen concentration of 0.60, and an inspiratory to expiratory ratio of 1∶2. Left and right myocardial systolic and diastolic function related parameters, including LVEF, LV global longitudinal strain (LVGLS), tricuspid annulus plane systolic migration (TAPSE), the peak early diastolic velocity (E peak) at the mitral and tricuspid valve ostia and the peak early diastolic velocity (e') at the corresponding annulus were measured by transesophageal echocardiography (TEE) before tracheal intubation (T 0), 5 minutes after the pneumoperitoneum (T 1), 5 minutes after PEEP ventilation (T 2), 30 minutes after PEEP ventilation (T 3), and 5 minutes after the end of pneumoperitoneum (T 4), respectively. The left and right ventricular myocardial performance index (LVMPI/RVMPI) was calculated. Results:Finally, 60 patients were included in the analysis, including 28 patients in the early LV diastolic dysfunction group and 32 patients in the normal cardiac function group. Compared with those at T 0, mean arterial pressure (MAP), LVEF, mitral e', LVGLS, tricuspid e' and TAPSE were significantly lower in the normal cardiac function group at T 1, and the early LV diastolic dysfunction group at T 1, T 2, and T 3, and LVMPI, LVE/e', RVE/e', and RVMPI were significantly higher. At T 4, the LVE/e' and the RVE/e' were significantly higher in the early LV diastolic dysfunction group than those at T 0 (LVE/e': 16.52±1.26 vs. 14.32±1.09, and RVE/e': 18.71±1.74 vs. 16.51±1.93, respectively, both P < 0.05), Mitral e' and tricuspid e' were significantly lower than those at T 0 [mitral e' (m/s): 0.07±0.01 vs. 0.09±0.01, tricuspid e' (m/s): 0.06±0.01 vs. 0.08±0.01, both P < 0.05]. Compared with the normal cardiac function group, MAP, LVEF, mitral e', LVGLS, tricuspid e', and TAPSE at T 1, T 2, and T 3 were significantly lower in the early LV diastolic dysfunction group, while LVMPI, LVE/e', RVE/e', and RVMPI were significantly higher. At T 4, the LVE/e' and the RVE/e' were significantly higher in the early LV diastolic dysfunction group than those in the normal cardiac function group (LVE/e': 16.52±1.26 vs. 9.87±1.25, RVE/e': 18.71±1.74 vs. 10.97±1.70, both P < 0.05). Mitral e' and tricuspid e' were significantly lower in the normal cardiac function group [mitral e' (m/s): 0.07±0.01 vs. 0.11±0.02, tricuspid e' (m/s): 0.06±0.01 vs. 0.10±0.02, both P < 0.05]. Conclusions:In early LV diastolic dysfunction patients, compared with patients with normal cardiac function, 5 cmH 2O PEEP can further exacerbate left and right myocardial systolic and diastolic function in patients during pneumoperitoneum; when the pneumoperitoneum was ended, 5 cmH 2O PEEP only worsen left and right myocardial diastolic function in patients, and did not affect left and right myocardial systolic function.

Objective:To evaluate the effect of driving pressure-guided individualized PEEP ventilation on intraoperative cardiac function in elderly patients undergoing laparoscopic surgery.Methods:Seventy American Society of Anesthesiologists physical statusⅠor Ⅱ patients, aged 60-75 yr, with body mass index of 18-25 kg/m 2, with left ventricular ejection fraction (LVEF)>50%, undergoing elective laparoscopic radical gastrectomy under general anesthesia, were divided into 2 groups ( n=35 each) by the random number table method: conventional PEEP ventilation group (group P) and driving pressure-guided individualized PEEP ventilation group (group D). The patients were mechanically ventilated in the volume-controlled ventilation mode, with a V T of 7 ml/kg, an inspired oxygen concentration of 60%, an inspiratory/expiratory ratio of 1∶2, and an end-inspiratory pause time of 10%.In group P, 5 cmH 2O PEEP was given for ventilation from 5 min after the establishment of pneumoperitoneum until the end of operation.In group D, driving pressure-guided individualized PEEP titration was performed at 5 min after the establishment of pneumoperitoneum, and ventilation was maintained with the titrated individualized PEEP until the pneumoperitoneum was closed.After the pneumoperitoneum was closed, group D underwent driving pressure-directed individualized PEEP again, and ventilation was maintained with re-titrated PEEP until the end of surgery.Before pneumoperitoneum (T 0), at 5 min after establishment of pneumoperitoneum (T 1), 5 min of PEEP ventilation (T 2), 30 min of PEEP ventilation (T 3) and 5 min after the end of pneumoperitoneum (T 4), MAP was recorded, LVEF, global longitudinal strain of left ventricle, tricuspid annular systolic displacement, early diastolic peak velocity (E peak) of mitral valve and tricuspid valve orifice, early diastolic peak velocity (e′) and systole peak velocity (S′) of mitral valve and tricuspid valve annulus were measured using transesophageal ultrasonography, and myocardial performance index (MPI) and E/e′ were calculated. Results:Compared with group P, MAP, LVEF, mitral valve annulus S′, global longitudinal strain of left ventricle, tricuspid valve annulus S′, and tricuspid annular systolic displacement were significantly decreased at T 2 and T 3, and left ventricular MPI, mitral valve E/e′, right ventricular MPI and tricuspid E/e′ were increased in group D ( P<0.05). Conclusions:Driving pressure-guided individualized PEEP ventilation can decrease the cardiac function during pneumoperitoneum in elderly patients undergoing laparoscopic surgery.