ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

ObjectiveTo investigate the correlation of the serum levels of aminotransferases and their ratios with liver inflammation activity in pediatric chronic hepatitis B （pCHB） patients， and to provide a basis for selecting the dominant population for treatment. MethodsThis study was conducted among 1 267 pCHB patients who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2010 to August 2022 and these patients did not receive antiviral therapy. The patients were analyzed in terms of demographic features， blood routine， blood biochemistry， HBV serological markers， and liver biopsy data. According to liver inflammation activity based on liver biopsy， the patients were divided into no or mild inflammation activity （G0‍ ‍—‍ ‍G1） group and significant inflammation activity （G2‍ ‍—‍ ‍G4） group. The serum levels of aminotransferases and their ratios were compared between groups， and their correlation with liver inflammation activity in pCHB patients was analyzed. Additionally， the patients were stratified by the age， and the relationship between serum aminotransferase levels and liver inflammation activity was analyzed in each age group. For comparison of continuous data between two groups， the independent samples t-test was used when the data were normally distributed， while the Mann-Whitney U test was used when the data were not normally distributed； the chi-square test was employed for comparison of categorical data between two groups. A Spearman’s correlation analysis was performed for correlation assessment. ResultsAmong the 1 267 pCHB patients， there were 468 （36.9%） in the G0‍ ‍—‍ ‍G1 group and 799 （63.1%） in the G2‍ ‍—‍ ‍G4 group， and there were significant differences between the two groups in the levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， AST/ALT ratio， gamma-glutamyl transpeptidase （GGT）， total bilirubin， direct bilirubin， HBeAg quantification， low-density lipoprotein， and platelet count （PLT） （all P<0.05）. The correlation analysis showed that liver inflammation activity was negatively correlated with PLT and low-density lipoprotein （both P<0.05） and was positively correlated with GGT， total bilirubin， direct bilirubin， and HBeAg titer （all P<0.05）， while it was not significantly correlated with ALT， AST， and AST/ALT ratio （all P>0.05）. In the 0‍ ‍—‍ ‍12 years group， the 13‍ ‍—‍ ‍18 years male group， and the 13‍ ‍—‍ ‍18 years female group， liver inflammation activity aggravated with the increases in the serum levels of ALT and AST， and there were significant differences between groups （all P<0.05）. In the 0‍ ‍—‍ ‍12 years group， there was a significant difference in significant liver inflammation activity between the AST/ALT ratio >1 group and the AST/ALT ratio ≤1 group （P<0.001）. Among the 1 267 patients， 447 （35.28%） had an ALT level of <2×upper limit of normal （ULN）， among whom 196 （43.85%） had G≥2 liver inflammation， accounting for 15.47% of all children enrolled. ConclusionLiver inflammation activity is not significantly correlated with ALT， AST， and AST/ALT ratio in pCHB patients， suggesting that the serum levels of aminotransferases cannot truly reflect liver inflammation activity in pCHB patients with an aminotransferase level of <2×ULN. In clinical practice， liver biopsy should be performed for children with an aminotransferase level of <2×ULN to clarify whether antiviral therapy should be performed.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Objective:To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases.Methods:Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated.Results:Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg -1·d -1 and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status ( OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication ( OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion:L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.

Objective To investigate the effect of palmitoleic acid(POA)on pyroptosis of cardiomyocytes after hy-poxia/reoxygenation-induced injury in the human myocardium.Methods The experiment comprised a control group(Control,normal culture),a hypoxia/reoxygenation group(HR),a palmitoleic acid-treated group(HR+POA),and an anhydrous ethanol control group(HR+ET).Cardiomyocytes viability was assessed using CCK-8 assay,and the level of pyroptosis of cardiomyocytes was measured through the double staining with Hoechst33342/PI and LDH assay.ELISA was employed to detect the release of inflammatory factors IL-1 β and IL-18 in the cell culture supernatant.qRT-PCR and Western blot were utilized to determine the relative expression levels of mRNA and protein of pyroptosis-related genes,namely NLRP3,ASC,Caspase-1,GSDMD,IL-1 β and IL-18,respective-ly.Results CCK-8 assay showed that the survival of hypoxic/reoxygenated cardiomyocytes increased with the ad-dition of POA at concentrations ranging from 25 to 100 μmol/L,as compared to the HR group;a hypoxia/reoxy-genation model of cardiomyocyte was established.The expression of protein and mRNA increased in NLRP3,ASC,Cleaved caspase-1,GSDMD-N,IL-Iβ and IL-18 vs the control group(P＜0.05),the positive percentage of Ho-echst33342/PI staining in cardiomyocytes increased significantly(P＜0.05),the release of LDH,IL-Iβ,and IL-18 increased(P＜0.05).After intervention with 100 μmol/L POA,the protein and mRNA expression levels of NLRP3,ASC,Cleaved caspase-1,GSDMD-N,IL-Iβ,and IL-18 were significantly reduced in the HR+POA group vs HR+ET group(P＜0.05).The positive percentage of Hoechst33342/PI staining in cardiomyocytes de-creased significantly,and the levels of LDH,IL-Iβ and IL-18 significantly decreased(P＜0.05).Conclusion Palmitoleic acid may alleviate hypoxia/reoxygenation-induced injury of cardiomyocytes by inhibiting pyroptosis and inflammatory response after hypoxia/reoxygenation in human myocardium.

The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
Humans ; Consensus ; Prone Position ; Wakefulness ; China ; Dyspnea

Objective:To explore the application effect of case-based learning (CBL), teaching mode combined with 3D printing in clinical teaching of sacral tumors.Methods:A total of 108 undergraduate interns and standardized residency training students who studied in our hospital from 2017 to 2018 were divided into the CBL teaching group ( n = 53) and the CBL combined with 3D printing teaching group ( n = 55) according to their study time. The combined teaching group used computer tomography (CT) data to reconstruct and print out a 3D model of sacral tumors based on CBL, and performed preoperative teaching on the invasion of the surrounding tissues of the tumor. The scores of the students in the two groups were evaluated respectively, and the students were surveyed by self-identification questionnaire (learning interest, self-learning ability, teamwork ability, comprehensive analysis ability and clinical thinking ability). The t-test (one-sided) was used for comparison between groups using stata 14.0. Results:The score of CBL teaching group (75.90±6.70) was lower than that of CBL combined with 3D printing teaching group (83.60±7.40). In terms of critical thinking ability evaluation, self-learning ability, learning interest, comprehensive analysis ability and clinical thinking ability, the CBL combined 3D printing teaching group was superior to the CBL teaching group, and the difference was statistically significant ( P<0.001). In terms of teamwork ability, there was no statistical difference between the two groups. Conclusion:The CBL teaching mode combined with 3D printing can improve academic performance, students' learning interest and clinical thinking ability of sacral tumors in the teaching of undergraduate interns and standardized residency training students.

Objective:To establish the Chinese version of (strength, assistance with walking, rise from a chair, climb stairs and falls, SARC-F) scale using the standardized methods and to validate the reliability and validity for sarcopenia screening among elderly population.Methods:Following the recommended procedure by World Health Organization and European Union Geriatric Medicine Society Sarcopenia Special Interest Group, the translation process included forward translation, expert panel, back-translation, pre-testing and cognitive interviewing to generate the final version. In the pilot study, the test-retest reliability, inter-rater reliability, and internal consistency of the Chinese version of SARC-F scale were assessed. In the diagnostic test for clinical validation, the participants were consecutively recruited from communities and hospitals in Beijing and Tianjin between December 2021 and October 2022. The scale administration, anthropometry, and body composition measurement were conducted by trained investigators. Participants with the SARC-F score ≥ 4 were considered at risk of sarcopenia. Diagnostic tests and receiver operating characteristic curve analysis were performed against the definitions of sarcopenia according to European Working Group on Sarcopenia in Older People (EWGSOP2) and Asian Working Group for Sarcopenia (AWGS2019), and the sensitivity, specificity, positive predictive value, negative predictive value and the area under curve were displayed.Results:The Chinese version of SARC-F scale was approved by the author that the translation has expressed the original meaning correctly. The Chinese version of SARC-F had good test-retest reliability (ICC = 0.914), inter-rater reliability ( r = 0.726), and internal consistency ( α = 0.729). There were altogether 1 882 participants included in the clinical validation. According to the diagnostic criteria of EWGSOP2 and AWGS2019, the Chinese version of SARC-F scale had low sensitivity (13.6% and 16.0%) and positive predictive value (44.6% and 35.4%), high specificity (95.1% and 94.7%) and negative predictive value (79.0% and 86.2%), and moderate AUC of 0.619 and 0.616 (all P < 0.001) for sarcopenia screening. Conclusions:The Chinese version of SARC-F scale was of good reliability and validity. The application of SARC-F in the primary healthcare settings would contribute to the early diagnosis of sarcopenia.