Objective To investigate the effects of exosomes (Exo) derived from high glucose-stimulated glomerular mesangial cells (GMC) on the kidneys of C57BL/6 mice and the intervention mechanism of Tongluo Yishen Formula (TLYSF). Methods The rat GMC were divided into a normal glucose group (NG, with 5.6 mmol/L glucose) and a high glucose group (HG, with 30 mmol/L glucose). After 24 hours of culture, the supernatant was collected, and exosomes were extracted using the ultracentrifugation method. The exosomes were then identified by transmission electron microscopy and Western blot analysis. Male C57BL/6 mice were divided into three groups: NO-Exo group, NG-Exo group, and HG-Exo group. These groups were respectively administered tail vein injections of PBS buffer, exosomes derived from GMC cultured in normal glucose, and exosomes derived from GMC cultured in high glucose, three times a week for a total of 8 weeks. After 8 weeks, the mice in the HG-Exo group were randomly divided into three subgroups: the HG-Exo group [gavaged with saline], the HG-Exo+TLYSF group [gavaged with TLYSF at 34.32 g/(kg.d)], and the HG-Exo + VAL group [gavaged with valsartan suspension at 10.4 mg/(kg.d)], and the intervention lasted for 4 weeks. Urinary microalbumin (mALb), urinary N-acetyl-β-D-aminoglucosidase (NAG), glycated hemoglobin (HbA1c), serum creatinine (Scr) and urea nitrogen (BUN) were detected. Transmission electron microscopy was used to observe the ultrastructure of renal tissues. TUNEL was used to detect the DNA damage of renal tissue cells. Immunofluorescence was used to detect the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and wilms tumor 1(WT-1). RT-PCR was used to detect the mRNA levels of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), interleukin-1 beta (IL-1β), miR-200c-3p and miR-148a-3p. Western Blot was employed to detect the protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 and IL-1β. Results Compared with the NG-Exo group, mice in the HG-Exo group exhibited significantly increased levels of mALb, urinary NAG, Scr and BUN. Transmission electron microscopy revealed ruptured podocyte membranes and swollen mitochondria. The positive rate of cells stained by the TUNEL increased, with elevated optical density of NLRP3 and decreased optical density of WT-1. Additionally, there was a significant increase in the level of NLRP3, caspase-1, IL-1β mRNA, as well as miR-200c-3p and miR-148a-3p. The protein expression of NLRP3, ASC, caspase-1, and IL-1β also increased. Compared with HG-Exo group, mice in the HG-Exo+TLYSF group showed decreased levels of mALb, urinary NAG, Scr, and BUN. The podocyte membranes were relatively intact, and mitochondrial damage was alleviated. The positive rate of cells stained by the TUNEL decreased, along with a reduction in the optical density of NLRP3 and an increase in the optical density of WT-1. Furthermore, the mRNA expression levels of NLRP3, caspase-1, IL-1β, miR-200c-3p, and miR-148a-3p were all downregulated to varying degrees. The protein expression levels of NLRP3, ASC, caspase-1, and IL-1β also decreased. Conclusion Exosomes derived from GMC stimulated by high glucose can damage the kidneys of mice and induce podocyte pyroptosis. TLYSF may ameliorate podocyte pyroptosis by downregulating the expression of exosomal miR-200c-3p and miR-148a-3p and inhibiting the activation of the NLRP3/ASC/caspase-1 pathway.
Animals ; Exosomes/ultrastructure* ; Glucose/pharmacology* ; Male ; Podocytes/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Mesangial Cells/metabolism* ; Pyroptosis/drug effects* ; Rats ; MicroRNAs/genetics*

Objective:To explore the mechanism of Zhuanggu Zhitong Prescription in preventing and treating postmenopausal osteoporosis.Methods:Rats were randomly divided into blank group, model group, Zhuanggu Zhitong Prescription high-, medium-, and low-dosage groups, and an estradiol group, with 10 rats in each group. Except for the blank group, all other groups of rats underwent bilateral oophorectomy to remove the ovaries, in order to prepare a postmenopausal osteoporosis rat model. On the 5th day after modeling, the blank group and model group were orally administered with 0.9% NaCl physiological saline, Zhuanggu Zhitong Prescription high-, medium-, and low-dosage groups were orally administered with 13.2, 8.2, and 3.3 g/kg of Zhuanggu Zhitong Prescription, and the estradiol group was orally administered with 0.016 7 g/100 g estradiol aqueous solution once a day for 12 consecutive weeks. The bone density of the lumbar spine in rats was measured; immunohistochemistry and Western blot were used to detect the expressions of Notch1, Jagged1, and Hes1 proteins; PCR was used to detect the mRNA levels of Notch1, Jagged1, and Hes1 in rats.Results:Compared with the model group, the bone density of rats in each group significantly increased ( P<0.01), the protein and mRNA levels of Notch1 and Jagged1 increased ( P<0.01), and the protein and mRNA levels of Hes1 decreased ( P<0.01). Conclusions:Zhuanggu Zhitong Prescription can improve bone mineral density in castrated osteoporosis rats, promote the increase and thickening of trabeculae of femoral bone in rats, promote bone formation, and further prevent osteoporosis. The mechanism may be related to the activation of Notch signaling pathway, up-regulation of Notch1 and Jagged1 proteins, and decrease of Hes1 protein expression, thus promoting bone differentiation.

Objective:To investigate the risk factors for severe hyperbilirubinemia complicated by acute bilirubin encephalopathy (ABE), and the value of total serum bilirubin (TSB) and bilirubin (B)/albumin (A) ratio in predicting ABE.Methods:Clinical data of children with severe hyperbilirubinemia admitted to the Affiliated Hospital of Inner Mongolia Medical University, Ordos Central Hospital, People's Hospital of Inner Mongolia Autonomous Region, the Fourth Hospital of Baotou, Tongliao Hospital, Maternal and Child Health Hospital of Hohhot, the Affiliated Hospital of Chifeng University, Manzhouli People's Hospital, and Chifeng Hospital from January 1, 2020, to December 31, 2021, were retrospectively collected. The subjects were divided into ABE and non-ABE groups based on the occurrence of ABE. Multivariate logistic regression analysis was used to identify high-risk factors for ABE. Statistical analysis was performed using t-test, Wilcoxon signed-rank test, or Chi-square tests. Indicators with statistically significant differences were included in the multivariate logistic regression model, and stepwise regression was used to analyze the influencing factors of ABE. Results:(1) A total of 543 children were included in this study, accounting for 3.7% (543/14 831) of the total admissions during the same period. Among the 543 children, 81 (14.9%) had ABE, and 462 (85.1%) did not. The age at admission was (7.2±2.1) d, and the length of hospital stay was (5.2±2.2) d. The breastfeeding initiation time was 2 d (1-4 d) after birth. The peak TSB of the 543 cases was (385.98±51.22) μmol/L, and the age at peak TSB was (4.4±2.1) d. Fourteen cases (2.5%) gradually reached the peak TSB after admission [(392.01±61.24) μmol/L], while 529 cases (97.5%) had already reached the peak TSB at admission [(386.42±50.22) μmol/L]. Among the 543 cases, 356 had a clear etiology (65.6%, with 278 cases having a single cause and 78 cases having more than two causes), and 187 cases (34.4%) had an unknown etiology. (2) Compared with the non-ABE group, the breastfeeding initiation in the ABE group was later [6 h (2-6 h) vs. 2 h (1-3 h), Z=－6.87] and the length of hospital stay was longer [(6.5±1.9) d vs. (5.0±2.1) d, t=0.55]. The proportions of breastfeeding, delayed meconium passage, isoimmune hemolysis, and maternal gestational diabetes, as well as peak TSB and B/A ratio at peak TSB, were higher in the ABE group than in the non-ABE group [64.2% (52/81) vs. 36.8% (170/462), χ2=21.96; 16.0% (13/81) vs. 2.4% (11/462), χ2=27.32; 27.2% (22/81) vs. 10.6% (40/462), χ2=16.61; 24.7% (20/81) vs. 13.6% (63/462), χ2=6.50; (442±68) vs. (375±39) μmol/L, t=－8.55; (11.9±1.6) vs. (9.8±1.2), t=－11.61; all P<0.05]. The admission weight, proportion of transfer from the hospital's obstetrics department, unknown etiology, and breast milk jaundice were lower in the ABE group than in the non-ABE group [(3 098±482) vs. (3 278±493) g, t=3.04; 12.3% (10/81) vs. 42.4% (196/462), χ2=30.48; 3.7% (3/81) vs. 39.8% (184/462), χ2=39.83; 0.0% (0/81) vs. 5.8% (27/462), χ2=3.81; all P<0.05]. (3) Isoimmune hemolysis, peak TSB, and B/A ratio at peak TSB were independent risk factors for ABE [ OR(95% CI) were 2.924 (1.209-7.073), 1.006 (0.997-1.014), and 2.647 (1.841-3.805), respectively]. When the peak TSB was 380.05 μmol/L and the B/A ratio at peak TSB was 10.45, the sensitivity for predicting ABE was 0.963, the specificity was 0.789, and the area under the receiver operating characteristic curve was 0.752. Conclusions:Isoimmune hemolysis, peak TSB, and B/A ratio at peak TSB are independent risk factors for ABE. The B/A ratio at peak TSB and peak TSB can effectively predict ABE.

The rapid development of digital intelligence technologies is providing a powerful boost to the high-quality development of the healthcare system.Considering the current state of our healthcare services and guided by General Secretary Xi Jinping's insights on new quality productive forces and the directives from Third Plenary Session of Communist Party of China's 20th Central Committee,the high-quality development of the healthcare service system should focus on digital intelligence technologies such as cloud computing,big data,privacy computing,blockchain,Internet of Things(IoT),mobile computing,and AI.The key measures should include the optimization of production factors,services,and governance.Emphasis should be placed on enhancing the efficient and intensive development of the development model,ensuring the high-quality and continuous integration of the supply model,and transitioning to scientific and modern management methods.Herein,we analyzed the"factor optimization—service optimization—governance optimization"development mechanism driven by digital intelligence and proposed corresponding implementation pathways,intending to provide references for establishing a high-quality and efficient healthcare service system with Chinese characteristics.

Objective:To investigate the risk factors for severe hyperbilirubinemia complicated by acute bilirubin encephalopathy (ABE), and the value of total serum bilirubin (TSB) and bilirubin (B)/albumin (A) ratio in predicting ABE.Methods:Clinical data of children with severe hyperbilirubinemia admitted to the Affiliated Hospital of Inner Mongolia Medical University, Ordos Central Hospital, People's Hospital of Inner Mongolia Autonomous Region, the Fourth Hospital of Baotou, Tongliao Hospital, Maternal and Child Health Hospital of Hohhot, the Affiliated Hospital of Chifeng University, Manzhouli People's Hospital, and Chifeng Hospital from January 1, 2020, to December 31, 2021, were retrospectively collected. The subjects were divided into ABE and non-ABE groups based on the occurrence of ABE. Multivariate logistic regression analysis was used to identify high-risk factors for ABE. Statistical analysis was performed using t-test, Wilcoxon signed-rank test, or Chi-square tests. Indicators with statistically significant differences were included in the multivariate logistic regression model, and stepwise regression was used to analyze the influencing factors of ABE. Results:(1) A total of 543 children were included in this study, accounting for 3.7% (543/14 831) of the total admissions during the same period. Among the 543 children, 81 (14.9%) had ABE, and 462 (85.1%) did not. The age at admission was (7.2±2.1) d, and the length of hospital stay was (5.2±2.2) d. The breastfeeding initiation time was 2 d (1-4 d) after birth. The peak TSB of the 543 cases was (385.98±51.22) μmol/L, and the age at peak TSB was (4.4±2.1) d. Fourteen cases (2.5%) gradually reached the peak TSB after admission [(392.01±61.24) μmol/L], while 529 cases (97.5%) had already reached the peak TSB at admission [(386.42±50.22) μmol/L]. Among the 543 cases, 356 had a clear etiology (65.6%, with 278 cases having a single cause and 78 cases having more than two causes), and 187 cases (34.4%) had an unknown etiology. (2) Compared with the non-ABE group, the breastfeeding initiation in the ABE group was later [6 h (2-6 h) vs. 2 h (1-3 h), Z=－6.87] and the length of hospital stay was longer [(6.5±1.9) d vs. (5.0±2.1) d, t=0.55]. The proportions of breastfeeding, delayed meconium passage, isoimmune hemolysis, and maternal gestational diabetes, as well as peak TSB and B/A ratio at peak TSB, were higher in the ABE group than in the non-ABE group [64.2% (52/81) vs. 36.8% (170/462), χ2=21.96; 16.0% (13/81) vs. 2.4% (11/462), χ2=27.32; 27.2% (22/81) vs. 10.6% (40/462), χ2=16.61; 24.7% (20/81) vs. 13.6% (63/462), χ2=6.50; (442±68) vs. (375±39) μmol/L, t=－8.55; (11.9±1.6) vs. (9.8±1.2), t=－11.61; all P<0.05]. The admission weight, proportion of transfer from the hospital's obstetrics department, unknown etiology, and breast milk jaundice were lower in the ABE group than in the non-ABE group [(3 098±482) vs. (3 278±493) g, t=3.04; 12.3% (10/81) vs. 42.4% (196/462), χ2=30.48; 3.7% (3/81) vs. 39.8% (184/462), χ2=39.83; 0.0% (0/81) vs. 5.8% (27/462), χ2=3.81; all P<0.05]. (3) Isoimmune hemolysis, peak TSB, and B/A ratio at peak TSB were independent risk factors for ABE [ OR(95% CI) were 2.924 (1.209-7.073), 1.006 (0.997-1.014), and 2.647 (1.841-3.805), respectively]. When the peak TSB was 380.05 μmol/L and the B/A ratio at peak TSB was 10.45, the sensitivity for predicting ABE was 0.963, the specificity was 0.789, and the area under the receiver operating characteristic curve was 0.752. Conclusions:Isoimmune hemolysis, peak TSB, and B/A ratio at peak TSB are independent risk factors for ABE. The B/A ratio at peak TSB and peak TSB can effectively predict ABE.

Recombinant collagen, as an alternative to natural collagen, has the potential to be widely used in biomaterials, biomedicine, etc. Diverse recombinant collagens and their variants can be industrially produced in a variety of expression systems, which lays a foundation for exploring and expanding the clinical application of recombinant collagens. We reviewed different expression systems for recombinant collagens, such as prokaryotic expression systems, yeast expression systems, as well as plant, insect, mammal, and human cell expression systems, and introduced the advantages, potential applications, and limitations of recombinant collagen. In particularly, we focused on the current progress in the recombinant collagen production, including recombinant expression system construction and hydroxylation strategies of recombinant collagen, and summarized the current biomedical applications of recombinant collagen.
Animals ; Biocompatible Materials ; Collagen/biosynthesis* ; Humans ; Hydroxylation ; Recombinant Proteins/biosynthesis*

Objective:To investigate the influential factors of internal fixation for closed posterior ankle fractures.Methods:The clinical data of 352 patients with closed ankle fractures who received treatment in Yeda Hospital from January 2016 to June 2020 were retrospectively analyzed. Among the 352 patients, 232 patients had posterior ankle fractures. These patients were grouped according to whether they had undergone internal fixation. The factors that affect internal fixation for closed posterior ankle fractures were analyzed by univariate and multivariate analyses.Results:232 patients out of 352 patients with closed ankle fractures had closed posterior ankle fractures, accounting for 65.91%. A total of 102 (43.97%) patients with posterior ankle fractures underwent internal fixation. There were significant differences in Bartonicek classification, the proportion of the posterior subluxation of the talus, the proportion of posterior ankle bone area, the proportion of posterior ankle bone area ≥ 25% displayed on X-ray image, the proportion of posterior ankle bone area ≥ 15% displayed on CT scan, the proportion of outward displacement of bone mass (92.31% vs. 41.82%) and the proportion of die-punch bone mass (94.23% vs. 40.00%) between patients receiving and not receiving internal fixation ( χ2 = 3.89, 0.26, 1.51, 0.31, 9.27, 8.67, 1.68, 5.84, 10.33, 12.47, 11.48, 10.69, 1.39, all P < 0.05). Multivariate analysis of a logistic regression model showed that posterior subluxation of the talus and the proportion of posterior ankle bone area ≥ 15% displayed on CT scan were independent influential factors of internal fixation for closed posterior ankle fracture ( OR = 5.47, 9.29, 95% CI:1.62-9.75, 3.24-27.01, all P < 0.05). Conclusion:In patients with closed ankle fractures, posterior ankle fractures and internal fixation are more common. At the same time, the posterior subluxation of the talus and the proportion of posterior ankle bone area ≥ 15% displayed on CT scan are closely related to receiving internal fixation.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective: To understand the fruit consumption of adults of Qingdao and examine the association between fruit consumption and stroke. Methods: We analyzed baseline data and stroke incidence of the participants who were aged 30-79 years and had been enrolled into the China Kadoorie Biobank (CKB) study from Qingdao city. Cox proportional hazards regression model was conducted to estimate the association of fruit consumption with risk of stroke. Results: A total of 35 509 participants were investgated in the baseline survey. Ratio of male to female was 1∶1.27, and the average age was (50.3±10.2) years. Respondents with higher frequency of fruit consumption were younger, more women, with higher education level and higher income (P<0.05). A total of 1 011 new cases of stroke were observed, with a stroke incidence of 387.63/100 000 person-years. Multivariate Cox regression analysis showed that fruit consumption had a protective effect on stroke incidence. Compared to the respondents who never consumed fruit, respondents who consumed fruit more than 4 days per week had a 44% lower risk of stroke incidence (HR=0.56, 95%CI: 0.50-0.62, P<0.05), and the risk reduced by 46% (HR=0.54, 95%CI: 0.46-0.64, P<0.05) and 42% (HR=0.58, 95%CI: 0.52-0.69, P<0.05) in male and female, respectively. Further adjustment for WC, BMI, SBP and random blood glucose did not change the association. Conclusion Increasing fruit consumption can effectively decrease the risk of stroke. People should increase fruit consumption advisably to set up reasonable and healthy dietary habits.