Diabetic kidney disease （DKD）， a prevalent microvascular complication of diabetes mellitus， is characterized by intricate pathophysiological mechanisms and persistent clinical management challenges. Historically， glomerular injury has been regarded as the central pathological hallmark of DKD， with research predominantly focusing on hyperfiltration， glomerular basement membrane thickening， and podocyte dysfunction. Emerging evidence， however， underscores the renal tubule-not merely as a passive bystander but as an early initiator and pivotal driver-in DKD pathogenesis. Hyperglycemia， metabolic dysregulation， and chronic low-grade inflammation induce tubular epithelial cell injury at early disease stages. Such injury disrupts tubuloglomerular feedback， thereby elevating intraglomerular pressure and sustaining hyperfiltration. Concurrently， injured tubular cells secrete pro-inflammatory cytokines and profibrotic factors， promoting epithelia-mesenchymal transition， interstitial hypoxia， and progressive tubulointerstitial fibrosis that ultimately culminate in irreversible decline of renal function. This "tubule-first" paradigm represents a fundamental shift from the classical glomerulocentric model and redefines the conceptual framework of DKD progression. Traditional Chinese medicine（TCM）， with its inherent advantages of multi-component synergy， multi-target engagement， and systemic homeostatic regulation， has demonstrated compelling renoprotective effect， particularly in preserving tubular integrity and function， mitigating tubular cellular stress， and indirectly alleviating glomerular hemodynamic burden. Accumulating preclinical and clinical evidence supports the efficacy of numerous single herbs and standardized formulae of TCM in attenuating tubulointerstitial injury and slowing down DKD progression. This review systematically delineates the sequential pathogenic cascade-from initial tubular insult to secondary glomerular deterioration-and critically evaluates the mechanism basis and translational potential of TCM-based interventions targeting tubular resilience. We aim to provide a refined pathophysiological rationale and actionable insights for optimizing clinical strategies and accelerating the development of novel therapeutics for DKD.

Diabetic kidney disease （DKD）， a prevalent microvascular complication of diabetes mellitus， is characterized by intricate pathophysiological mechanisms and persistent clinical management challenges. Historically， glomerular injury has been regarded as the central pathological hallmark of DKD， with research predominantly focusing on hyperfiltration， glomerular basement membrane thickening， and podocyte dysfunction. Emerging evidence， however， underscores the renal tubule-not merely as a passive bystander but as an early initiator and pivotal driver-in DKD pathogenesis. Hyperglycemia， metabolic dysregulation， and chronic low-grade inflammation induce tubular epithelial cell injury at early disease stages. Such injury disrupts tubuloglomerular feedback， thereby elevating intraglomerular pressure and sustaining hyperfiltration. Concurrently， injured tubular cells secrete pro-inflammatory cytokines and profibrotic factors， promoting epithelia-mesenchymal transition， interstitial hypoxia， and progressive tubulointerstitial fibrosis that ultimately culminate in irreversible decline of renal function. This "tubule-first" paradigm represents a fundamental shift from the classical glomerulocentric model and redefines the conceptual framework of DKD progression. Traditional Chinese medicine（TCM）， with its inherent advantages of multi-component synergy， multi-target engagement， and systemic homeostatic regulation， has demonstrated compelling renoprotective effect， particularly in preserving tubular integrity and function， mitigating tubular cellular stress， and indirectly alleviating glomerular hemodynamic burden. Accumulating preclinical and clinical evidence supports the efficacy of numerous single herbs and standardized formulae of TCM in attenuating tubulointerstitial injury and slowing down DKD progression. This review systematically delineates the sequential pathogenic cascade-from initial tubular insult to secondary glomerular deterioration-and critically evaluates the mechanism basis and translational potential of TCM-based interventions targeting tubular resilience. We aim to provide a refined pathophysiological rationale and actionable insights for optimizing clinical strategies and accelerating the development of novel therapeutics for DKD.

The automation technology of surgical robots(SR)integrates key techniques such as force feedback,visual feedback,medical image alignment,and surgical navigation.This integration not only effectively reduces the workload of surgeons,enabling them to focus more on the overall execution of the surgical procedure,but also decreases reliance on surgical experience,contributing to the standardization and homogenization of surgical outcomes.Although most current SR systems are primarily used for assisting operations,some robots have demonstrated conditional automation capabilities,showcasing significant potential in automated surgery research.However,the development of automated surgery still faces numerous challenges,including limited perception capabilities,constraints of artificial intelligence algorithms,and technical bottlenecks in surgical navigation.This paper summarizes the key technologies of commonly used SR systems globally,analyzes the progress in automation research,and discusses the challenges and trends in future development.

The automation technology of surgical robots(SR)integrates key techniques such as force feedback,visual feedback,medical image alignment,and surgical navigation.This integration not only effectively reduces the workload of surgeons,enabling them to focus more on the overall execution of the surgical procedure,but also decreases reliance on surgical experience,contributing to the standardization and homogenization of surgical outcomes.Although most current SR systems are primarily used for assisting operations,some robots have demonstrated conditional automation capabilities,showcasing significant potential in automated surgery research.However,the development of automated surgery still faces numerous challenges,including limited perception capabilities,constraints of artificial intelligence algorithms,and technical bottlenecks in surgical navigation.This paper summarizes the key technologies of commonly used SR systems globally,analyzes the progress in automation research,and discusses the challenges and trends in future development.

Objective:To investigate the mechanism of Yunshi Ganmao Heji against respiratory syncytial virus (RSV) infection based on network pharmacology and in vivo experiments. Methods:Network pharmacological prediction: Several databases including TCMSP and GeneCards were used to predict the active ingredients and targets of Yunshi Ganmao Heji in the intervention of RSV infection. Cytoscape 3.2.1 software was used to construct the traditional Chinese medicine component-disease target network diagram. The interactions between proteins were analyzed by STRING database. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using Metascape database. Molecular docking technology was used to verify the results of network pharmacology. Experimental verification of Yunshi Ganmao Heji for the intervention of RSV infection: A mouse model of RSV infection was established through intranasal infection. After the administration of Yunshi Ganmao Heji, blood routine test results, lung indexes and pathological changes in lung tissue were analyzed. Peripheral blood T cell subsets were detected by flow cytometry. The levels of TNF-α, IL-6 and IL-1β in serum were detected by ELISA. RT-PCR was used to detect the relative expression of TLR4, NF-κB and RSV-N gene at mRNA level in lung tissues.Results:A total of 41 active ingredients of Yunshi Ganmao Heji and 111 drug targets for RSV infection were obtained. Besides, 167 signaling pathways mainly including PI3K/AKT, MAPK and Toll-like receptor signaling pathways were obtained. Molecular docking results showed that the binding energies of luteotin, kaempferol and quercetin, three active ingredients of Yunshi Ganmao Heji, with RSV-G, RSV-F, PI3K, AKT1 and Bcl-2 were less than 0 kcal/mol. In vivo experiment results showed that compared with RSV group, the counts of white blood cells and lymphocytes increased and the lung index decreased in high-dose Yunshi Ganmao Heji group, with statistically significant difference ( P<0.05). HE staining showed pulmonary hyperplasia, thickened alveolar wall and inflammatory cell infiltration in interstitium in RSV group. Alveoli in ribavirin group as well as low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups tended to be of uniform size, and the alveolar walls was roughly uniform in thickness. Compared with RSV group, the low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups showed significantly increased numbers of CD3 +, CD4 + and CD8 + T lymphocytes, decreased CD4 + /CD8 + T cell ratio, lower levels of TNF-α, IL-6, IL-1β in serum, and reduced viral load and inhibited expression of TLR4 and NF-κB at mRNA level in lung tissues ( P<0.05). Conclusions:Yunshi Ganmao Heji can regulate RSV infection by targeting multiple targets and pathways with several active ingredients. Its main functions are to alleviate pathological injury in lung tissues and reduce inflammatory response, and the possible mechanism underlying the antiviral functions may be related to its inhibitory effect on the activation of TLR4/NF-κB pathway.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To investigate the role and mechanism of mitochondrial DNA N6-methyladenine (6mA) in the hippocampal neurons in vascular cognitive impairment.Methods:(1) In vivo experiments: SPF male rats were randomly divided into sham-operated group and chronic cerebral hypoperfusion (CCH) group ( n=12). CCH models in the CCH group were established by ligating bilateral carotid arteries, while rats in the sham-operated group were only bilaterally dissected without ligation. Exploratory ability was detected by open field test 50 d after modeling, cognitive function was evaluated by novel object recognition test 51-53 d after modeling, and learning and memory abilities were tested by Morris water maze 54-59 d after modeling. And then, rats were sacrificed; ATP concentration and reactive oxygen species (ROS) level in the hippocampal tissues were detected, and neuron apoptosis in the hippocampal CA1 area was detected by TUNEL. (2) In vitro experiments: HT-22 cells were divided into normal control (NC) group, oxygen-glucose deprivation (OGD) group, OGD+siControl group, and OGD+siMETTL4 group. Cells in the NC group were cultured routinely, cells in the OGD group were subjected to low sugar and low oxygen for 12 h, and cells in the OGD+siControl group and OGD+siMETTL4 group were, respectively, transfected with NC-siRNA or METTL4-siRNA after being subjected to low sugar and low oxygen for 12 h. Mitochondria morphology was observed by transmission electron microscopy, ROS was detected by flow cytometry, mitochondria membrane potential was detected by JC-1 fluorescent staining, and mitochondrial complex I and III activity was detected by kit. (3) In vivo and in vitro experiments: METTL4 and DNA 6mA expressions in neuronal mitochondria of rat hippocampal tissues and mitochondria of HT-22 cells were detected by immunofluorescent staining and Western blotting. Results:(1) CCH rats had cognitive impairment: compared with the sham-operated group, CCH group had significantly increased frequency of entering the central area and reduced time in exploring new objects in open field experiment,and significantly decreased frequency of crossing the platform and prolonged escape latency in water maze experiment ( P<0.05). Compared with rats in the sham-operated group, rats in the CCH group had significantly decreased hippocampal ATP content ([18.820±1.177] nmol/L vs. [10.190±0.519] nmol/L) and increased ROS content ([4 488.00±255.70] AU vs. [11 644.00±530.20] AU, P<0.05). TUNEL results showed that the number of apoptotic neurons in the hippocampal CA1 area of CCH group was obviously increased than that in sham-operated group. Immunofluorescent staining results showed that 6mA and METTL4 mainly distributed in the mitochondria of hippocampal neurons in CCH group, and the 6mA and METTL4 expressions were obviously increased compared with those in the sham-operated group. Western blotting results showed that METTL4 expression in the hippocampal mitochondria of CCH group was significantly higher than that in the sham-operated group (1.729±0.168 vs. 1.000±0.000). (2) In vitro experiment: under transmission electron microscope, compared with the NC group, HT-22 cells in the OGD group showed obvious mitochondrial ridge disappearance, membrane rupture and vacuolation. Compared with the OGD group, the OGD+siMETTL4 group had significantly increased ATP production, decreased mtROS production, increased mitochondrial membrane potential, and increased mitochondrial complex I and III activities ( P<0.05). Immunofluorescent staining results showed that the mtDNA 6mA and METTL4 expressions in the OGD group were obviously higher than those in the NC group, and both mainly expressed in the mitochondria; mtDNA 6mA expression in the OGD+siMETTL4 group was obviously lower than that in OGD group. Western blotting results showed that METTL4 expression in the OGD+siMETTL4 group was significantly higher than that in the OGD group (1.578±0.261 vs. 2.970±0.280). Conclusion:Specific high expression of methylase METTL4 in hippocampal neurons of rats with cognitive impairment after CCH promotes the increased mtDNA 6mA expression and leads to mitochondrial energy metabolism disorders and increased ROS, which is speculated to be one of the mechanisms causing vascular cognitive impairment.

ObjectiveTo explore the mechanism of Huanglian Ejiaotang in intervening in insomnia based on 5-hydroxytryptamine （5-HT） system and gut microbiota. MethodFifty-five SPF-grade SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose Huanglian Ejiaotang groups （1.925， 3.85， and 7.7 g·kg^-1）， and Estazolam group （0.1 mg·kg^-1）. Except for those in the normal group， the rats in the other five groups were subjected to sleep deprivation on a narrow platform for 12 hours daily for 21 consecutive days. After 14 days of drug intervention， the sleep， exploratory behavior， and depressive-like behavior of the rats were assessed using the pentobarbital sodium sleep synergistic test， the open field test， and the sugar preference test， respectively. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of 5-HT， 5-hydroxyindoleacetic acid （5-HIAA）， tryptophan hydroxylase （TPH）， and monoamine oxidase-A （MAO-A）. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of the 5-HT1A receptor （5-HT1AR） and 5-HT2A receptor （5-HT2AR）. Differences in gut microbiota among the groups were assessed using 16S rRNA sequencing， and the correlation between the 5-HT system and microbiota was revealed using redundancy analysis. ResultCompared with the normal group， the model group showed a prolonged sleep latency （P<0.05）， reduced sleep maintenance （P<0.01）， decreased central area activity time in the open field （P<0.01）， and reduced sugar preference rate （P<0.05）. Moreover， the model group also showed decreased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， decreased 5-HIAA/5-HT ratio （P<0.01）， downregulated mRNA expression of 5-HT1AR （P<0.01）， and upregulated mRNA expression of 5-HT2AR （P<0.05）. The proportion of Firmicutes decreased， while that of Bacteroidetes increased， leading to a decreased Firmicutes/Bacteroidetes （F/B） ratio （P<0.05）. Compared with the model group， the high-dose Huanglian Ejiaotang group exhibited a shortened sleep latency （P<0.01）， and increased sleep maintenance （P<0.01）. The low-dose Huanglian Ejiaotang group showed increased central area activity time （P<0.01） and an increased sugar preference rate （P<0.05）. The high-dose Huanglian Ejiaotang group exhibited increased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， increased 5-HIAA/5-HT ratio （P<0.05）， upregulated mRNA expression of 5-HT1AR （P<0.01）， and downregulated mRNA expression of 5-HT2AR （P<0.05）. The low-dose Huanglian Ejiaotang group displayed an increased proportion of Firmicutes and a decreased proportion of Bacteroidetes， resulting in an increased F/B ratio. At the phylum level， 5-HT， 5-HIAA， and MAO-A were positively correlated with Firmicutes and negatively correlated with Bacteroidetes. At the genus level， 5-HT， 5-HIAA， TPH， and MAO-A were negatively correlated with Prevotella and Lactobacillus and positively correlated with Blautia and Bacteroides. ConclusionHuanglian Ejiaotang can improve sleep deprivation-induced insomnia and depressive-like behavior by regulating the activity of the 5-HT system and the composition of gut microbiota.

Objective To investigate the association between baseline IgM level and treatment response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). Methods A retrospective analysis was performed for the clinical data of 637 PBC patients who were diagnosed and treated with UDCA for the first time in The Fifth Medical Center of Chinese PLA General Hospital from January 2010 to January 2020. The PBC patients were divided into UDCA complete response group with 436 patients and UDCA poor response group with 201 patients, and baseline clinical data were compared between the two groups. According to the optimal cut-off value of IgM determined by the area under the ROC curve (AUC) of baseline indices in predicting the risk of poor treatment response, the patients were divided into IgM ≥1.5×ULN group and IgM < 1.5×ULN group, and baseline parameters, treatment response, and prognostic model score were compared between groups. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Cochran-Mantel-Haenszel test was used for subgroup analysis, and forest plots were plotted for related risk values. Results Compared with the UDCA complete response group, the UDCA poor response group had significantly higher proportion of patients with liver cirrhosis, levels of total bilirubin, aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid, total cholesterol (TC), IgA, and IgM, and positive rate of anti-Gp210 antibody at baseline ( χ 2 =4.596, Z =-9.932, -8.931, -8.361, -7.836, -4.694, -3.242, and -2.115, χ 2 =15.931, all P < 0.05). The UDCA poor response group had significantly higher Mayo Risk Score, Globe score, and UK-PBC risk score than the UDCA complete response group ( t =4.092, Z =-10.910 and -11.646, all P < 0.001). Compared with the normal IgM group, the elevated IgM group had significantly higher levels of AST, ALP, TC, IgA, and IgG and a significantly higher positive rate of anti-Gp210 antibody ( Z =-3.774, -5.063, -4.344, -2.051, and -6.144, χ 2 =25.180, all P < 0.05). IgM had an AUC of 0.552 in predicting poor treatment response. Compared with the IgM < 1.5×ULN group, the IgM ≥1.5×ULN group had significantly higher levels of AST, ALP, TC, and IgG, a significantly higher positive rate of anti-Gp210 antibody, and a significantly higher poor UDCA response rate ( Z =-4.193, -5.044, -3.250, and -5.465, χ 2 =25.204 and 8.948, all P < 0.05). IgM ≥1.5×ULN had an odds ratio of 1.416 (95% confidence interval [ CI ]: 1.129-1.776, P =0.003) in predicting poor response. The subgroup analysis showed that for patients without liver cirrhosis, IgM ≥1.5×ULN had an odds ratio of 1.821 (95% CI : 1.224-2.711, P =0.003) in predicting poor response. Conclusion Baseline IgM level has an important value in predicting UDCA response. IgM level should be closely monitored during treatment in PBC patients with a high baseline IgM level, and second-line drugs should be given in time if the abnormality persists.

Objective:To investigate the protective effect of carbon monoxide releasing molecule 2 (CORM-2) on intestinal barrier by regulating the differentiation of T lymphocytes in rats with hemorrhagic shock.Methods:Healthy male Sprague-Dawley rats ( n=56) were randomly (random number) divided into the sham operation group, shock group, dimethyl sulfoxide (DMSO) control group, inactivated carbon monoxide release molecule-2 (iCORM-2) pretreatment group and three pretreatment CORM-2 with the doses of 2, 4 and 6 mg/kg separately. The hemorrhagic shock was induced with the use of a modified Wiggers model. Rats in the CORM-2 group and iCORM-2 group were intraperitoneally injected with CORM-2 with the doses of 2, 4 and 6 mg/kg and 6 mg/kg iCORM-2 instantly before shock induction. Rats in the DMSO group received intraperitoneal administration of 2% DMSO with the same volume of iCORM-2. Rats in the shock group and sham operation group were not pretreated before inducing shock. Mean arterial pressure of each rat was recorded at different phases after catheterization or shock. Twenty-three hours after shock induction, the permeability of intestinal barrier was measured by FITC-dextran flux, and then ileum tissues were harvested to observe histopathologic changes. Immunohistochemistry was used to detect the expression of transcription factors T-bet and Foxp3 of intestinal mucosa in rats, and the expression of interferon-γ (IFN-γ), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in intestinal mucosa was measured by Western blot. One-way analysis of variance or Kruskal Wallis rank sum test was used to compare the difference among groups for normal or non-normal distributed data. Results:Compared with the sham operation group, serum concentrations of FITC-dextran were significantly increased in the shock group, DMSO group and iCORM-2 group (all P<0.05). The concentrations of FITC-dextran in serum of three CORM-2 pretreatment groups pretreatment were significantly decreased compared with other groups undergoing shock (all P<0.05). Rats in the shock group, DMSO group and iCORM-2 group showed severe ileum injury. CORM-2 intervention resulted in alleviation of intestinal mucosal injury in rats with shock, and rats in groups pretreatment CORM-2 at the doses of 4 and 6 mg/kg exhibited integrity of anatomic ileac structure. Compared with the sham operation group, T-bet levels of intestinal intraepithelial lymphocytes were increased in shock group and DMSO group (all P<0.05). Compared with the shock group, levels of T-bet were decreased in intestinal epithelium of three groups pretreatment with CORM-2 at the doses of 2, 4 and 6 mg/kg (all P<0.05). Foxp3 levels in intestinal intraepithelial lymphocytes of the iCORM-2 group and two groups pretreatment with CORM-2 at the doses of 4 and 6 mg/kg were increased compared with the shock group and DMSO group (all P<0.05), but there was no significant difference among the shock group, DMSO group and group pretreatment with CORM-2 at 6 mg/kg (all P>0.05). The shock group showed increased expression of IFN-γ (all P<0.05), but unchangeable expression of IL-10 and TGF-β (all P>0.05) compared with the sham operation group. Compared with the shock group, the expression levels of IL-10 in three groups pretreatment with CORM-2 at the doses of 2, 4 and 6 mg/kg were significantly increased (all P<0.05), and the expression levels of TGF-β were increased in two groups pretreatment with CORM-2 at the doses of 4 and 6 mg/kg (all P<0.05). The expression of IFN-γ in group pretreatment with CORM-2 at 6 mg/kg was significantly decreased compared with the shock group ( P<0.05). Conclusions:CORM-2 inhibited the activation of type 1 helper T cells to decrease the expression of proinflammatory factors and upregulated the expression of anti-inflammatory factors. Thus, CORM-2 reduced gut inflammation and protected the intestinal barrier.