ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Objective To construct a predictive model for the survival of transplant kidneys after kidney transplantation. Methods The clinical data of 366 kidney transplant recipients and donors were retrospectively analyzed, and the recipients were divided into low-risk group (n=101), medium-risk group (n=189), and high-risk group (n=76) based on the kidney donor profile index (KDPI). Each group was further divided into Remuzzi score ≤3 group and Remuzzi score >3 group based on time-zero biopsy Remuzzi scores. Kaplan-Meier method was used to analyze the survival of transplant kidneys. Univariate and multivariate Cox regression analyses were performed to identify risk factors affecting long-term survival after kidney transplantation. A predictive model for transplant kidney survival was established and a nomogram was drawn. The predictive performance of the model was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results The median KDPI was 65%, and the median Remuzzi score was 3. The 5-year survival rate of transplant kidneys was 83.5%. Kaplan-Meier survival curves showed that in the KDPI medium-risk and KDPI high-risk groups, the subgroup with lower Remuzzi score had a higher survival rates of transplant kidneys than the subgroup with higher Remuzzi score. Univariate and multivariate Cox regression analyses showed that KDPI, Remuzzi score, and donor’s age were independent risk factors for transplant kidney loss (all P<0.05). The ROC curve showed that the AUC of the nomogram prediction model established based on independent risk factors for the 1, 3 and 5-year survival rates of transplant kidneys were 0.91, 0.93 and 0.94 for the training set, and 0.89, 0.85 and 0.88 for the validation set. Calibration curves shows good consistency between the training and validation sets of the model. Conclusions The nomogram predictive model based on KDPI, time-zero biopsy Remuzzi score and donor’s age has good predictive value for transplant kidney survival.

BACKGROUND:It has been confirmed that the mixing of decellularized matrix and polymer electrospinning can not only improve the structural properties of fibers,but also preserve the biological decellularized of decellularized matrix.However,there is no relevant report on the preparation of skin tissue engineering scaffolds by electrospinning polyurethane and decellularized skin matrix. OBJECTIVE:To investigate the reparative effect of a decellularized skin matrix/polyurethane blended fibrous scaffold on rat skin defects. METHODS:Polyurethane electrospun fibrous scaffold and decellularized skin matrix/polyurethane blended fibrous scaffold were fabricated using the electrospinning technique.The fiber structure was observed under scanning electron microscope.Rat adipose mesenchymal stem cells were inoculated on two kinds of scaffolds respectively.The morphology of the scaffolds was observed under scanning electron microscope.Three full-thickness skin defects of 1 cm×1 cm were fabricated on the back of 10 SD rats.Polyurethane electrospun fibrous scaffolds(control group)and decellularized skin matrix/polyurethane blended fibrous scaffolds(experimental group)were implanted in two of the defects,and no material was implanted in the remaining defects(blank control group).The skin wound healing was observed at 1,2,and 3 weeks after operation.At 3 weeks after implantation,the wound was stained with hematoxylin and eosin and the scar area was calculated. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the two kinds of electrospun fibers were reticulated,and the rat adipose mesenchymal stem cells attached to the fibers on the two kinds of scaffolds,and the adhesion was good.(2)With the extension of the postoperative time,the skin wounds of each group gradually healed.By week 3 after the operation,the skin wounds of the experimental group and the control group were basically healed,and small ulcers could be seen on the wounds of the blank control group.Hematoxylin-eosin staining of skin wounds showed that the epidermal coverage of the wound was basically complete in the control group and the experimental group,and fibroblast growth and inflammatory cell infiltration could be seen in the dermis.In addition,the collagen fibers of the wound in the experimental group were abundant and arranged in a regular order,basically parallel to the epidermal surface.The wound epidermis of blank control group was still defective.The scar area of the experimental group was smaller than that of the other two groups(P<0.05,P<0.01).(3)These results indicate that the decellularized skin matrix/polyurethane blended fibrous scaffold can effectively repair full-thickness skin defects and improve scar formation in rats.

The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

AIM: To investigate the correlation between the expression of serum lipocalin 2(LCN2), chemokine like receptor 1(CMKLR1), and C-C motif chemokine ligand 11(CCL11)and the severity of disease in patients with type 2 diabetes mellitus(T2DM)and dry eye(DE).METHODS:A prospective selection of 97 patients(194 eyes)diagnosed with T2DM and DE at our hospital from May 2022 to May 2024 was made as the DE group, which was further divided into mild(47 cases, 94 eyes), moderate(34 cases, 68 eyes), and severe(16 cases, 32 eyes)subgroups based on the severity of dry eye. Additionally, 97 patients(194 eyes)of T2DM without DE were selected as non-DE group, and 97 healthy volunteers(194 eyes)who underwent physical examination during the same period were chosen as control group. Serum levels of LCN2, CMKLR1, and CCL11 were measured in all participants. Spearman correlation analysis was used to assess the relationship between serum levels of LCN2, CMKLR1, and CCL11 and the severity of DE in T2DM patients; multivariate Logistic analysis was used to analyze the factors affecting the severity of T2DM patients with DE. The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum LCN2, CMKLR1 and CCL11 levels for moderate to severe dry eye in T2DM patients.RESULTS: Serum levels of LCN2, CMKLR1, and CCL11 increased progressively from the control group to the non-DE group and then to the DE group(all P<0.05). Within the DE group, these levels also increased progressively from the mild to moderate and then to the severe subgroups(all P<0.05). Spearman correlation analysis showed that serum levels of LCN2, CMKLR1, and CCL11 were positively correlated with the severity of disease(rs=0.604, 0.591, 0.559, respectively; all P<0.05). Stepwise forward multivariate Logistic analysis showed that Schirmer's test(SⅠt), tear break-up time(BUT), serum levels of LCN2, CMKLR1 and CCL11 were the factors affecting the severity of T2DM patients with DE; ROC curve analysis indicated that the combined diagnosis of serum LCN2, CMKLR1, and CCL11 for the progression of T2DM with DE to moderate-to-severe stages had an area under curve(AUC)value of 0.896, which was significantly higher than that of individual diagnoses of LCN2, CMKLR1, and CCL11(Z=2.925, 2.704, 3.483, respectively; P=0.003, 0.007, <0.001).CONCLUSION: Serum LCN2, CMKLR1 and CCL11 levels are increased in T2DM patients with DE, and are positively correlated with the severity of DE. The combination of the three has a high diagnostic value for moderate to severe DE.

Objective To evaluate the value of an optimized three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with a longer repetition time (TR, 16 000 ms) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in the endolymphatic hydrops (EH) imaging after intratympanic gadolinium (Gd) administration, and to compare it with a conventional 3D-real IR based on the turbo spin echo (TSE) sequence. Methods From July 2021 to November 2022, twenty-seven patients received both the conventional and optimized 3D-real IR sequences after bilateral intratympanic Gd administration. Images of the two sequences were qualitativly evaluated and compared. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and area ratio of endolymph against the total lymphatic space from the two sequences were measured and compared. Results 14(25.9%) ears with insufficient contrast for the EH diagnosis on the conventional sequence were clearly displayed on the optimized sequence. Image score, CNR and SNR of the optimized sequence were significantly higher than those of the conventional sequence (P ＜ 0.001). The scanning time of two sequences was similar. The area ratio of endolymph against the total lymphatic space in the cochlear was significantly higher on the conventional 3D-real IR than that on the optimized 3D-real IR (P ＜ 0.001); there was no statistical difference in the vestibule between the two sequences. Conclusions Compared with conventional sequence, optimized 3D-real IR sequence with a longer TR may be better for evaluation of EH after intratympanic Gd administration.

Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P＜0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P＜0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.

ObjectiveTo investigate the role of silent information regulatory protein （SIRT6）/hypoxia-inducible factor-1α （HIF-1α） pathway in regulating the reprogramming of glucose metabolism in ulcerative colitis （UC） and the mechanism of intervention of Shaoyaotang. MethodsForty-eight c57bL/6 mice were randomly divided into a blank group， a model group， a Mesalazine group （0.42 g·kg^-1）， a Shaoyaotang group （31.08 g·kg^-1）， an inhibitor group （OSS-128167， 50 mg·kg^-1）， and an inhibitor + Shaoyaotang group （50 mg·kg^-1 OSS-128167 + 31.08 g·kg^-1 Shaoyaotang）. A UC model was established by the administration of 2.5% dextran sulfate sodium （DSS） solution for mice in other groups for 7 d， except for the blank group. The mice in each group were treated with saline， Mesalazine， Shaoyaotang， inhibitor， and inhibitor + Shaoyaotang， respectively， for 7 d. The mice were necropsied 24 h after the last administration of the drug. The blood was collected from the orbital region， and colon tissue was taken. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect serum interleukin （IL）-10， IL-17， and IL-6 levels. A biochemical method was used to detect glucose and lactate dehydrogenase A （LDHA） levels. Immunohistochemistry （IHC） was employed to detect IL-22 and transforming growth factor-β₁ （TGF-β₁） levels in colon tissue， and Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect relative protein and mRNA expressions of SIRT6， HIF-1α， and LDHA. ResultsCompared with those of the blank group， disease activity index （DAI） scores of mice in the model group and inhibitor group were significantly increased （P<0.01）. The length of colon tissue was significantly shortened， and colon tissue was congested and eroded. The pathohistological scores were significantly increased （P<0.01）. The levels of serum inflammatory factors IL-17 and IL-6 were significantly elevated， and the levels of IL-10 were significantly decreased （P<0.01）. The protein expressions of IL-22 and TGF-β₁ were significantly reduced in colon tissue （P<0.01）. The relative protein and mRNA expressions of SIRT6 were significantly decreased （P<0.01）， and the relative protein and mRNA expressions of HIF-1α and LDHA and the contents of glucose and lactate were significantly elevated （P<0.01）. The level of inflammation in the colon of the mice in the inhibitor group was more severe than that in the model group （P<0.01）. Compared with the model group， the Mesalazine group， the Shaoyaotang group， and the inhibitor + Shaoyaotang group showed reduced colonic injury， significant decrease in serum IL-17 and IL-6， significant increase in IL-10 （P<0.01）， significant increase in the protein expressions of IL-22 and TGF-β₁ in colon tissue （P<0.01）， significant increase in the protein expressions of SIRT6 and the relative mRNA expressions （P<0.01）， and significant reduction in the protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate （P<0.01）. Compared with those in the Shaoyaotang group， the serum IL-17 and IL-6 were significantly increased， and IL-10 was significantly decreased in the inhibitor + Shaoyaotang group （P<0.01）. The protein expressions of IL-22 and TGF-β₁ in colon tissue were significantly decreased （P<0.01）. The expressions of SIRT6 protein and the relative mRNA expressions were significantly decreased （P<0.01）. The protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate were significantly elevated （P<0.01）. However， the difference between the Shaoyaotang group and the Mesalazine group was not significant. ConclusionShaoyaotang can effectively treat DSS-induced mice with UC through the SIRT6/HIF-1α pathway， and its mechanism of action may be related to the regulation of the SIRT6/HIF-1α pathway and glucose metabolism reprogramming and the inhibition of glycolysis.

ObjectiveTo investigate the role of silent information regulatory protein （SIRT6）/hypoxia-inducible factor-1α （HIF-1α） pathway in regulating the reprogramming of glucose metabolism in ulcerative colitis （UC） and the mechanism of intervention of Shaoyaotang. MethodsForty-eight c57bL/6 mice were randomly divided into a blank group， a model group， a Mesalazine group （0.42 g·kg^-1）， a Shaoyaotang group （31.08 g·kg^-1）， an inhibitor group （OSS-128167， 50 mg·kg^-1）， and an inhibitor + Shaoyaotang group （50 mg·kg^-1 OSS-128167 + 31.08 g·kg^-1 Shaoyaotang）. A UC model was established by the administration of 2.5% dextran sulfate sodium （DSS） solution for mice in other groups for 7 d， except for the blank group. The mice in each group were treated with saline， Mesalazine， Shaoyaotang， inhibitor， and inhibitor + Shaoyaotang， respectively， for 7 d. The mice were necropsied 24 h after the last administration of the drug. The blood was collected from the orbital region， and colon tissue was taken. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect serum interleukin （IL）-10， IL-17， and IL-6 levels. A biochemical method was used to detect glucose and lactate dehydrogenase A （LDHA） levels. Immunohistochemistry （IHC） was employed to detect IL-22 and transforming growth factor-β₁ （TGF-β₁） levels in colon tissue， and Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect relative protein and mRNA expressions of SIRT6， HIF-1α， and LDHA. ResultsCompared with those of the blank group， disease activity index （DAI） scores of mice in the model group and inhibitor group were significantly increased （P<0.01）. The length of colon tissue was significantly shortened， and colon tissue was congested and eroded. The pathohistological scores were significantly increased （P<0.01）. The levels of serum inflammatory factors IL-17 and IL-6 were significantly elevated， and the levels of IL-10 were significantly decreased （P<0.01）. The protein expressions of IL-22 and TGF-β₁ were significantly reduced in colon tissue （P<0.01）. The relative protein and mRNA expressions of SIRT6 were significantly decreased （P<0.01）， and the relative protein and mRNA expressions of HIF-1α and LDHA and the contents of glucose and lactate were significantly elevated （P<0.01）. The level of inflammation in the colon of the mice in the inhibitor group was more severe than that in the model group （P<0.01）. Compared with the model group， the Mesalazine group， the Shaoyaotang group， and the inhibitor + Shaoyaotang group showed reduced colonic injury， significant decrease in serum IL-17 and IL-6， significant increase in IL-10 （P<0.01）， significant increase in the protein expressions of IL-22 and TGF-β₁ in colon tissue （P<0.01）， significant increase in the protein expressions of SIRT6 and the relative mRNA expressions （P<0.01）， and significant reduction in the protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate （P<0.01）. Compared with those in the Shaoyaotang group， the serum IL-17 and IL-6 were significantly increased， and IL-10 was significantly decreased in the inhibitor + Shaoyaotang group （P<0.01）. The protein expressions of IL-22 and TGF-β₁ in colon tissue were significantly decreased （P<0.01）. The expressions of SIRT6 protein and the relative mRNA expressions were significantly decreased （P<0.01）. The protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate were significantly elevated （P<0.01）. However， the difference between the Shaoyaotang group and the Mesalazine group was not significant. ConclusionShaoyaotang can effectively treat DSS-induced mice with UC through the SIRT6/HIF-1α pathway， and its mechanism of action may be related to the regulation of the SIRT6/HIF-1α pathway and glucose metabolism reprogramming and the inhibition of glycolysis.